正伴随着人口老化,与老龄化相关的各种神经退行性疾病会严重影响老年期生活质量。其中,主观认知下降(subjective cognitive decline,SCD)是影响老年期生活质量的重要问题之一,并可能由此而发展成阿尔茨海默病(Alzheimer's disease,AD)痴呆。AD是老年痴呆最常见病因,是一种渐进性的神经系统退行性疾病,从AD临床前期SCD,到轻度认知障碍(mild cognitive impairment,MCI),再到AD痴[1]

阿尔兹海默症(AD)的发展是个长期的过程,在疾病最初始阶段——主观记忆减退阶段,开展有针对性的干预是延缓AD进程的有效切入点.目前针对主观记忆减退老年人的可塑性研究处于起步阶段,仅有的少数认知训练研究提示主观记忆减退老年人的认知功能仍具有一定的可塑性.迫切需要设计严谨、测查指标丰富的设计来探讨认知训练对延缓主观记忆减退老年人认知老化,并进一步预防AD等神经退行性疾病发生的影响.

Accumulating evidence suggests that subjective cognitive complaints (SCC) may indicate subtle cognitive decline characteristic of individuals with preclinical Alzheimer’s disease (AD). In this study, we sought to build upon previous studies by associating SCC and amyloid-β deposition using positron emission tomography with Pittsburgh Compound B (PiB-PET) in cognitively normal older individuals. One-hundred thirty one subjects (mean age 73.5±6) were administered three subjective cognitive questionnaires and a brief neuropsychological battery. A relationship between a subjective memory complaints composite score and cortical PiB binding was found to be significant, even after controlling for depressive symptoms. By contrast, there were no significant relationships between objective cognitive measures of memory and executive functions and cortical PiB binding. Our study suggests that SCC may be an early indicator of AD pathology detectable prior to significant objective impairment.

OBJECTIVES: To examine the association between the type and number of subjective memory complaints (SMCs) and performance on objective cognitive tests.DESIGN: Cross-sectional.SETTING: Nurses' Health Study.PARTICIPANTS: Sixteen thousand nine hundred sixty-four women (mean age 74) who provided information on SMCs.MEASUREMENTS: Telephone cognitive assessments and seven questions regarding SMCs were administered. Cognitive impairment was defined as a score of less than 31 on the Telephone Interview for Cognitive Status (TICS) and below the 10th percentile on other cognitive measures. To assess associations with SMCs, multivariable logistic regression was used to calculate odds ratios for cognitive impairment and multivariable linear regression to calculate mean differences in cognitive test scores, adjusting for age and depressive symptoms.RESULTS: Some SMCs, such as trouble following a group conversation or finding one's way around familiar streets, were more highly associated than others with odds of cognitive impairment. The complaint of forgetting things from one second to the next, generally considered part of normal aging, was not associated with cognitive impairment. In addition, there were strong, linear trends of increasingly worse scores on cognitive tests with increasing numbers of memory complaints. For each additional SMC endorsed, the odds of cognitive impairment increased approximately 20% when each SMC was weighted equally.CONCLUSION: SMCs are associated with objective cognitive status and may be considered by primary care physicians in determining whether follow-up is warranted.

Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Background We investigated the effects of multiple-modality exercise with additional mind-motor training on cognition in community-dwelling older adults with subjective cognitive complaints. Methods Participants (n = 127, mean age 67.5 [7.3] years, 71% women) were randomized to receive 45 minutes of multiple-modality exercise with additional 15 minutes of either mind-motor training (M4, n = 63) or control (balance, range of motion and breathing exercises [M2, n = 64]). In total, both groups exercised 60 minutes/day, 3 days/week, for 24 weeks. Standardized global cognitive functioning (GCF), concentration, reasoning, planning, and memory were assessed at 24 weeks and after a 28-week no-contact follow-up. Results There were no significant differences in the study primary outcomes. The M4 group, however, showed trends for greater improvements in GCF and memory (both, P = .07) compared to the M2 group at 24 weeks. Significant differences between group in GCF (P = .03) and memory (P = .02) were observed after the 28-week no-contact follow-up favouring the M4 group. Discussion Additional mind-motor training did not impart immediate greater benefits to cognition among the study participants.

The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk. To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11-labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β65=650.35; 95% CI, 0.19-.52; P65<65.001) and Aβ burden (β65=650.24; 95% CI, 0.08-.40; P65=65.005), but not inferior temporal tau burden (β65=650.10; 95% CI, -0.08 to 0.28; P65=65.27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for Aβ burden (β65=650.36; 95% CI, 0.15-.58; P65=65.001), and no interaction influenced SCD (β65=65-0.36; 95% CI, -0.34 to 0.09; P65=65.25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.

The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high β-amyloid burden (CN Aβ+). Fifty-eight CN Aβ+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed. In CN Aβ+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio02=025.1; 95% confidence interval, 1.4–20.0,P=02.02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippocampal volume. High SMD is a harbinger of greater rates of clinical progression in preclinical AD. Although SMD reflects broader diagnostic implications for CN Aβ+, more sensitive measures may be required to detect early subtle cognitive change.

Abstract OBJECTIVES: (i) To analyze if general cognitive performance, perceived health and depression are predictors of Subjective Memory Complaints (SMC) contrasting their effect sizes; (ii) to analyze the relationship between SMC and objective memory by comparing a test that measures memory in daily life and a classical test of associated pairs; (iii) to examine if different subgroups, formed according to the MFE score, might have different behaviors regarding the studied variables. METHODS: Sample: 3921 community-dwelling people (mean age 70.41卤4.70) without cognitive impairment. Consecutive non-probabilistic recruitment. ASSESSMENT: Mini Cognitive Exam (MCE), daily memory Rivermead Behavioural Memory Test (RBMT), Paired Associates Learning (PAL), Geriatric Depression Scale (GDS), Nottingham Health Profile (NHP). Dependent variable: Memory Failures Everyday Questionnaire (MFE). RESULTS: Two different dimensions to explain SMC were found: One subjective (MFE, GDS, NHP) and other objective (RBMT, PAL, MCE), the first more strongly associated with SMC. SMC predictors were NHP, GDS, RBMT and PAL, in this order according to effect size. Considering MFE scores we subdivided the sample into three groups (low, medium, higher scores): low MFE group was associated with GDS; medium, with GDS, NPH and RBMT, and higher, with age as well. Effect size for every variable tended to grow as the MFE score was higher. CONCLUSION: SMC were associated with both health profile and depressive symptoms and, in a lesser degree, with memory and overall cognitive performance. In people with fewer SMC, these are only associated with depressive symptomatology. More SMC are associated with depression, poor health perception and lower memory. Copyright 2016 Elsevier Ireland Ltd. All rights reserved.

The objective of this study is to compare three different interventions for persons who report memory difficulties: health promotion, cognitive training, and a participation-centered course, using a single-blind, randomized controlled design.Participants were 44 Israeli adults with memory complaints, aged 65 years or older. The main outcome variable was the Global Cognitive Score assessed using the MindStreams(庐) mild cognitive impairment assessment, a computerized cognitive assessment. The Mini-Mental State Examination and the self-report of memory difficulties were also utilized. To assess well-being, the UCLA Loneliness Scale-8 was used. Health was evaluated by self-report instruments.All three interventions resulted in significant improvement in cognitive function as measured by the computerized cognitive assessment. All approaches seemed to decrease loneliness. The only variable which showed a significant difference among the groups is the self-report of memory difficulties, in which the cognitive training group participants reported greater improvement than the other groups.Multiple approaches should be offered to older persons with memory complaints. The availability of diverse options would help fit the needs of a heterogeneous population. An educational media effort to promote the public's understanding of the efficacy of these multiple approaches is needed.

Subjective (SCI) refers to concerns regarding one's cognitive functioning in the absence of objective evidence of impairment, and may represent an early stage of . However, as not all individuals with SCI cognitively decline, there is growing interest in the early identification of those individuals with SCI who are most at risk of developing . One promising method of early identification involves the use of biomarkers that are known to be associated with the pathophysiology of the disease; in particular, markers of amyloid and tau accumulation. While there has been substantial research on amyloid and tau biomarkers in the context of (), only recently has attention shifted to SCI, which may represent an even earlier stage in the disease course. The purpose of this paper is to qualitatively review the literature on amyloid and tau biomarkers in SCI. A brief discussion of non-amyloid/tau biomarkers is also included. Not surprisingly, we found that amyloid and tau biomarker profiles become increasingly abnormal from SCI, to , to . Additionally, although amyloid and tau biomarkers appear to be unable to differentiate between SCI and healthy controls, there is some evidence to suggest that they may be able to differentiate between those individuals with SCI who cognitively decline over time and those who do not. While this finding has potential clinical implications, achieving optimal predictive value will likely require further research into the use of numerous biomarkers in combination.

Pathophysiological changes that accompany early clinical symptoms in prodromal Alzheimer's disease (AD) may have a disruptive influence on brain networks. We investigated resting-state functional magnetic resonance imaging (rsfMRI), combined with brain connectomics, to assess changes in whole-brain functional connectivity (FC) in relation to neurocognitive variables. Participants included 58 older adults who underwent rsfMRI. Individual FC matrices were computed based on a 278-region parcellation. FastICA decomposition was performed on a matrix combining all subjects' FC. Each FC pattern was then used as a response in a multilinear regression model including neurocognitive variables associated with AD (cognitive complaint index [CCI] scores from self and informant, an episodic memory score, and an executive function score). Three connectivity independent component analysis (connICA) components (RSN, VIS, and FP-DMN FC patterns) associated with neurocognitive variables were identified based on prespecified criteria. RSN-pattern, characterized by increased FC within all resting-state networks, was negatively associated with self CCI. VIS-pattern, characterized by an increase in visual resting-state network, was negatively associated with CCI self or informant scores. FP-DMN-pattern, characterized by an increased interaction of frontoparietal and default mode networks (DMN), was positively associated with verbal episodic memory. Specific patterns of FC were differently associated with neurocognitive variables thought to change early in the course of AD. An integrative connectomics approach relating cognition to changes in FC may help identify preclinical and early prodromal stages of AD and help elucidate the complex relationship between subjective and objective indices of cognitive decline and differences in brain functional organization.

Background: Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Methods: Cognitively normal elderly participants of the German Study on Ageing, Cognition, and... [Show full abstract]

What did you have for breakfast yesterday? Who went with you to the movies? Who did you see at work today? It is likely that you can answer all questions of this sort. Moreover, if you continue to focus on retrieving information relevant to one or more of these questions, you will recover an amazing amount of contextual detail that surrounded the personal experience. Now answer another question: Did you intend to remember any of these experiences? The likely answer in most cases will be no. Thus, this small exercise reveals that your brain contains a memory system that automatically captures the content of your daily life and stores it in a manner that permits you to intentionally retrieve and replay it.

Abstract Subjective memory impairment (SMI) is a common risk factor for Alzheimer's disease, with few established options for treatment. Here we investigate the effects of two months episodic memory training on regional brain atrophy in 19 memory clinic patients with SMI. We used a sensitive longitudinal magnetic resonance imaging protocol and compared the patients with 42 matched healthy volunteers randomly assigned to a group performing the same training, or a no-training control group. Following intervention, the SMI sample exhibited structural gray matter volume increases in brain regions encompassing the episodic memory network, with cortical volume expansion of comparable extent as healthy training participants. Further, we found significant hippocampal volume increases in the healthy training group but not in the SMI group. Still, individual differences in left hippocampal volume change in the patient group were related to verbal recall improvement following training. The present results reinforce earlier studies indicating intact brain plasticity in aging, and further suggest that training-related brain changes can be evident also in the earliest form of cognitive impairment.

Accumulating evidence suggests that the mere subjective feeling of memory impairment in the absence of objective cognitive deficits may precede mild cognitive impairment in the continuum of Alzheimer disease manifestation. Brain imaging studies have provided insights into structural and functional alterations at the clinical stages of dementia and mild cognitive impairment, but the functional characteristics of subjective memory impairment (SMI) are largely unstudied.

Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer’s disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions.

Functional neuroimaging studies of retrieval show consistent activation of the right prefrontal and superior parietal cortex. We examined the specific role of the prefrontal cortex during retrieval with the hypothesis that this region mediates monitoring processes necessary for optimal recall. During functional neuroimaging with PET, subjects retrieved verbal material under two conditions. In the first, an organizational structure had been provided, prior to scanning, and this formed the basis for a monitored search while the scan took place. A comparison condition did not require a monitored search because recall was externally cued. In both conditions, when compared with baseline tasks prefrontal cortex and medial parietal activation was observed. Within the right prefrontal cortex activation an anatomical dissociation was seen between the dorsal and ventral prefrontal cortex. The dorsal region showed greater activation when monitoring demands were emphasized, while the ventral region showed greater activation when external cueing was emphasized. An unpredicted dissociation within the superior parietal activation was also observed, a dorsal region showing activation during the monitored search task and a more ventral region showing activation under the externally cued condition. The results provide evidence for functional specialization of the right prefrontal cortex for discrete cognitive processes during episodic retrieval.

Current evidence supports the concept of a preclinical phase of Alzheimer's disease (AD) where pathological and imaging changes are present in asymptomatic individuals. Subjective cognitive impairment (SCI) may represent the earliest point on the continuum of AD. A better understanding of the baseline characteristics of this group of patients that later decline in cognition will enhance our knowledge of the very early disease processes, facilitate preventive strategies, early diagnosis, timely follow-up and treatment. An observational exploratory study which followed up 62 consecutive patients with SCI presenting to a memory clinic and compared baseline characteristics of SCI patients who declined cognitively with those who did not. Cognitive decline was defined as a progression to a diagnosis of amnestic mild cognitive impairment (aMCI) or dementia at follow-up. Patients were followed up for a mean of 44 months (range 12-112 months). At the time of follow up, 24% of patients had declined. Patients that declined were significantly older at onset of symptoms and first presentation to memory clinic, and took significantly more medications for physical illnesses. Patients that declined also performed significantly worse on Trail Making Test (TMT) B and Cambridge Cognitive Examination Revised (CAMCOG-R) at baseline. Survival analysis identified key variables that predicted decline (later age of onset and later age at first assessment). Patients who present with subjective memory complaints and are over the age of 61 years are at high risk of cognitive decline and warrant an in-depth assessment and follow-up.

A voxel-based method of measuring the effective connectivity between brain regions is presented. The approach is based on electrophysiological concepts and is applied to neurophysiological data obtained with (positron emission tomography (PET)) functional imaging. Time-dependent changes in effective connectivity were assessed during a verbal fluency activation paradigm using 12 consecutive measurements of regional cerebral blood flow (rCBF). The changes observed were predicted by an associative (Hebbian) model of plasticity, applied to cortical activity, measured in terms of rCBF. The main finding was, in most regions, a selective enhancement of effective connections from the distributed brain regions exhibiting the dominant pattern of correlated activity.

Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. Lack of information about the early pathophysiology in AD complicates the search for therapeutic strategies. Subjective cognitive impairment is the description given to subjects who have memory-related complaints without pathological results on neuropsychological tests. There is no consensus regarding this heterogeneous syndrome, but at least some of these patients may represent the earliest stage in AD. We reviewed available literature in order to summarise current knowledge on subjective cognitive impairment. Although they may not present detectable signs of disease, SCI patients as a group score lower on neuropsychological tests than the general population does, and they also have a higher incidence of future cognitive decline. Depression and psychiatric co-morbidity play a role but cannot account for all cognitive complaints. Magnetic resonance imaging studies in these patients reveal a pattern of hippocampal atrophy similar to that of amnestic mild cognitive impairment and functional MRI shows increased activation during cognitive tasks which might indicate compensation for loss of function. Prevalence of an AD-like pattern of beta-amyloid (A42) and tau proteins in cerebrospinal fluid is higher in SCI patients than in the general population. Memory complaints are relevant symptoms and may predict AD. Interpatient variability and methodological differences between clinical studies make it difficult to assign a definition to this syndrome. In the future, having a standard definition and longitudinal studies with sufficient follow-up times and an emphasis on quantifiable variables may clarify aspects of early AD.

Abstract Age-related differences in brain activity mediating face recognition were examined using positron emission tomography. Participants encoded faces using a pleasant-unpleasant judgment, a right-left orientation task, and intentional learning. Scans also were obtained during recognition. Both young and old groups showed signficant effects of encoding task on recognition accuracy, but older adults showed reduced accuracy overall. Increased brain activity in older adults was similar to that seen in young adults during conditions associated with deeper processing, but was reduced during the shallow encoding and recognition conditions. Left prefrontal activity was less in older adults during encoding, but greater during recognition. Differential correlations of brain activity and behavior were found that suggest older adults use unique neural systems to facilitate face memory.

ObjectiveTo determine if functional connectivity of the hippocampus is reduced in patients with Alzheimer disease.DesignFunctional connectivity magnetic resonance imaging was used to investigate coherence in the magnetic resonance signal between the hippocampus and all other regions of the brain.ParticipantsEight patients with probable Alzheimer disease and 8 healthy volunteers.ResultsControl subjects showed hippocampal functional connectivity with diffuse cortical, subcortical, and cerebellar sites, while patients demonstrated markedly reduced functional connectivity, including an absence of connectivity with the frontal lobes.ConclusionThese findings suggest a functional disconnection between the hippocampus and other brain regions in patients with Alzheimer disease.

Previous research has shown that there is considerable overlap in the neural networks mediating successful memory encoding and retrieval. However, little is known about how the relevant human brain regions interact during these distinct phases of memory or how such interactions are affected by memory deficits that characterize mild cognitive impairment (MCI), a condition that often precedes dementia due to Alzheimer's disease. Here we employed multivariate Granger causality analysis using autoregressive modeling of inferred neuronal time series obtained by deconvolving the hemodynamic response function from measured blood oxygenation level-dependent (BOLD) time series data, in order to examine the effective connectivity between brain regions during successful encoding and/or retrieval of object location associations in MCI patients and comparable healthy older adults. During encoding, healthy older adults demonstrated a left hemisphere dominant pattern where the inferior frontal junction, anterior intraparietal sulcus (likely involving the parietal eye fields), and posterior cingulate cortex drove activation in most left hemisphere regions and virtually every right hemisphere region tested. These regions are part of a frontoparietal network that mediates top-down cognitive control and is implicated in successful memory formation. In contrast, in the MCI patients, the right frontal eye field drove activation in every left hemisphere region examined, suggesting reliance on more basic visual search processes. Retrieval in the healthy older adults was primarily driven by the right hippocampus with lesser contributions of the right anterior thalamic nuclei and right inferior frontal sulcus, consistent with theoretical models holding the hippocampus as critical for the successful retrieval of memories. The pattern differed in MCI patients, in whom the right inferior frontal junction and right anterior thalamus drove successful memory retrieval, reflecting the characteristic hippocampal dysfunction of these patients. These findings demonstrate that neural network interactions differ markedly between MCI patients and healthy older adults. Future efforts will investigate the impact of cognitive rehabilitation of memory on these connectivity patterns.

react-text: 127 It is commonly assumed that functional brain connectivity reflects structural brain connectivity. The exact relationship between structure and function, however, might not be straightforward. In this review we aim to examine how our understanding of the relationship between structure and function in the 'resting' brain has advanced over the last several years. We discuss eight articles that... /react-text react-text: 128 /react-text [Show full abstract]

Decline in associative memory abilities is a common cognitive complaint among older adults and is detectable in both normal aging and in prodromal Alzheimer’s disease (AD). Subjective memory (SM) complaints may serve as an earlier marker of these mnemonic changes; however, previous research examining the predictive utility of SM to observed memory performance yielded inconsistent results. This inconsistency is likely due to other sources of variance that occur with memory decline such as mood/depression issues, presence of apolipoprotein E (APOE ε4) genotype, or beta-amyloid deposition. Here we examine the relationship between SM and associative memory ability in the context of factors that increase susceptibility to AD in 195 healthy adults (79 men) aged 20–94 years. Participants completed an SM questionnaire, a mood/depression scale, two associative memory tests (a word-pair and a name-face test), and were genotyped for APOE ε4. PET-amyloid imaging data were collected for a subset of those over 50 years of age (N = 74). We found that SM predicted performance on both associative memory tests even after covarying for age, sex, mood, and APOE ε4 status. Interestingly, for the name-face associative task, increased SM concerns predicted memory performance selectively in participants over the age of 60, with the APOEε4 risk group showing the strongest effect. Finally, men with higher beta-amyloid deposition reported more memory complaints. Our findings suggest that SM reliably tracks memory performance, even in cognitively healthy adults, and may reflect an increased risk for AD. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

Abstract Aging researchers have long been interested in understanding individuals' subjective perceptions of their own memory functioning. Previous research has shown that subjective memory ratings are partly based on memory performance but also reflect the influence of other factors, such as depressive symptoms. The aim of the present study was to examine (1) longitudinal associations between trajectories of subjective memory and memory performance, (2) variables that predict levels of and changes in subjective memory and memory performance, and (3) variables that moderate associations between these constructs. We applied a latent growth curve model to four occasions of data from 15,824 participants of the Health and Retirement Study (HRS; mean age at baseline=64.27 years, SD=9.90; 58% women). Results revealed that latent changes in subjective memory were correlated with latent changes in memory performance (0.49), indicating that participants who reported steeper declines of subjective memory indeed showed steeper declines of memory performance over time. Three major patterns of associations emerged with respect to predictors of subjective memory and subjective memory change. First, the level of memory performance showed stronger associations with age, gender, and education, whereas subjective memory was more strongly associated with subjective age and personality traits. For example, women performed better than men on the episodic memory test, but there were no gender differences in subjective memory. Also, older age was associated with steeper declines of memory performance but with less decline of subjective memory. Second, personality traits that predicted subjective memory intercepts did not predict subjective memory slopes. Third, the strength of associations between levels and slopes of subjective memory and memory performance varied as a function of gender, education, depressive symptoms, and personality traits. Conscientiousness moderated the relationship of the level of subjective memory to the level of memory performance, consistent with the hypothesis that persons high in conscientiousness more accurately monitor memory successes and failures. The results reinforce the importance of depressive symptoms as a predictor of subjective memory but also indicate that a broader perspective on the reasons why memory complaints have modest correlations with memory itself is needed. 2015 S. Karger AG, Basel

A growing body of research has examined whether people’s judgments of their own memory functioning accurately reflect their memory performance at cross-section and over time. Relatively less is known about whether these judgments are specifically based on memory performance, or reflect general cognitive change. The aim of the present study was to examine longitudinal associations of subjective memory with performance in tests of episodic memory and a wide range of other cognitive tests, including the Wechsler Adult Intelligence Scale—Revised (WAIS–R) Block Design, Comprehension, Digit Span, Digit Symbol, and Vocabulary subtests. We applied latent growth curve models to five occasions over up to 16 years of neuropsychological assessments from 956 participants of the Seattle Longitudinal Study (SLS; 57% women; age at baseline: M = 65.1, SD = 11.4, 38 – 96 years). Results revealed that lower self-reported Frequency of Forgetting was significantly associated with better performance in all cognitive domains at baseline. The baseline correlation of Frequency of Forgetting with memory performance was stronger than its correlations with performance in other cognitive tests. Furthermore, additional analyses with baseline data showed that a latent memory performance factor reliably predicted Frequency of Forgetting after controlling for a general cognitive factor. Over time, steeper increases in Frequency of Forgetting were associated with steeper declines in tests of memory performance and in the Block Design and Digit Symbol subtests. Taken together, these findings suggest that although self-reported Frequency of Forgetting reflects performance in a broad range of other cognitive domains, it also shows some specificity for memory performance. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCDplus.

To examine the biological basis of subjective memory impairment (SMI), defined as the feeling of memory worsening with normal memory performance, we measured the volume of the entorhinal cortex (EC) and the hippocampus in SMI subjects, patients with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) and healthy controls (CO). Compared with controls, the EC was smaller in the SMI group (left: p = 0.060; right: p = 0.045) and in the other two groups in the following order: CO > SMI > MCI > AD. The same sequence was observed with regard to hippocampal volumes, but the volume reduction of the left hippocampus in the SMI group only reached a trend towards significance ( p = 0.072) and the right was not significantly smaller compared with controls ( p = 0.37). Compared with controls the average (left/right) volume reduction of the EC was 18% (SMI), 26% (MCI) and 44% (AD). The mean volume reduction of the hippocampus was 6% (SMI), 16% (MCI) and 19% (AD). Our results mirror the temporal sequence of neurodegeneration in AD and support the concept of SMI as the first clinical manifestation of dementia.

Subjective memory impairment (SMI) is receiving increasing attention as a pre-mild cognitive impairment (MCI) condition in the course of the clinical manifestation of Alzheimer disease (AD). To determine the risk for conversion to any dementia, dementia in AD, or vascular dementia by SMI, graded by the level of SMI-related worry and by the temporal association of SMI and subsequent MCI. Longitudinal cohort study with follow-up examinations at 1(1/2) and 3 years after baseline. Primary care medical record registry sample. A total of 2415 subjects without cognitive impairment 75 years or older in the German Study on Aging, Cognition and Dementia in Primary Care Patients. Conversion to any dementia, dementia in AD, or vascular dementia at follow-up 1 or follow-up 2 predicted by SMI with or without worry at baseline and at follow-up 2 predicted by different courses of SMI at baseline and MCI at follow-up 1. In the first analysis, SMI with worry at baseline was associated with greatest risk for conversion to any dementia (hazard ratio [HR], 3.53; 95% confidence interval [CI], 2.07-6.03) or dementia in AD (6.54; 2.82-15.20) at follow-up 1 or follow-up 2. The sensitivity was 69.0% and the specificity was 74.3% conversion to dementia in AD. In the second analysis, SMI at baseline and MCI at follow-up 1 were associated with greatest risk for conversion to any dementia (odds ratio [OR], 8.92; 95% CI, 3.69-21.60) or dementia in AD (19.33; 5.29-70.81) at follow-up 2. Furthermore, SMI at baseline and amnestic MCI at follow-up 1 increased the risk for conversion to any dementia (OR, 29.24; 95% CI, 8.75-97.78) or dementia in AD (60.28; 12.23-297.10), with a sensitivity of 66.7% and a specificity of 98.3% for conversion to dementia in AD. The prediction of dementia in AD by SMI with subsequent amnestic MCI supports the model of a consecutive 3-stage clinical manifestation of AD from SMI via MCI to dementia.

Abstract INTRODUCTION: Functional and cognitive features of subjective cognitive decline (SCD) were identified in a longitudinal database from the National Alzheimer's Coordinating Center. METHODS: Cognitively normal older adults with (SCD+) and without (SCD-) self-reported memory complaints (N0002=00023915) were compared on (1) baseline Functional Assessment Questionnaire ratings, (2) baseline scores and longitudinal rate of change estimates from nine neuropsychological tests, and (3) final clinical diagnoses. RESULTS: SCD+0002had higher baseline ratings of functional impairment, reduced episodic memory practice effects and poorer performance on neuropsychological tests of psychomotor speed and language, and higher frequencies of mild cognitive impairment and dementia diagnoses at the end of follow-up compared with the SCD-group. DISCUSSION: Subtle clinical features of SCD identified in this large cohort are difficult to detect at the individual level. More sensitive tests are needed to identify those with SCD who are vulnerable to cognitive decline and dementia. Copyright 0008 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Cognitively normal elderly participants of the German Study on Ageing, Cognition, and Dementia study (N = 2330) with SCD (subjective decline in memory with and without associated concerns) and without SCD at baseline were assessed over 8 years with regard to immediate and delayed verbal recall, verbal fluency, working memory, and global cognition. Baseline performance and cognitive trajectories were compared between groups. In addition, cognitive trajectories before and after the initial report of SCD (incident SCD) were modelled in those without SCD at baseline. Baseline performance in the SCD group was lower and declined more steeply in immediate and delayed verbal recall than in the control group (no SCD at baseline). This effect was more pronounced in the SCD group with concerns. Incident SCD was preceded by decline in immediate and delayed memory and word fluency. SCD predicts future memory decline. Incident SCD is related to previous cognitive decline. The latter finding supports the concept of SCD indicating first subtle decline in cognitive performance that characterizes preclinical Alzheimer's disease.

The findings suggested that a short memory questionnaire is useful in the screening of MCI, particularly in subjects who already present with subtle functioning disturbances. Subjective memory complaints were significant correlated with objective performance of memory functions, reflecting the usefulness of memory complaints in the assessment of MCI. Copyright 2005 John Wiley & Sons, Ltd.

A multistudy analysis of positron emission tomography data identified three right prefrontal and two left prefrontal cortical sites, as well as a region in the anterior cingulate gyrus, where neuronal activity is correlated with the maintenance of episodic memory retrieval mode (REMO), a basic and necessary condition of remembering past experiences. The right prefrontal sites were near the frontal pole [Brodmann's area (BA) 10], frontal operculum (BA 47/45), and lateral dorsal area (BA 8/9). The two left prefrontal sites were homotopical with the right frontal pole and opercular sites. The same kinds of REMO sites were not observed in any other cerebral region. Many previous functional neuroimaging studies of episodic memory retrieval have reported activations near the frontal REMO sites identified here, although their function has not been clear. Many of these, too, probably have signaled their involvement in REMO. We propose that REMO activations largely if not entirely account for the frontal hemispheric asymmetry of retrieval as described by the original hemispheric encoding retrieval asymmetry model.

Elderly individuals with subjective impairment (SMI) report decline, but perform within the age-, gender-, and education- adjusted normal range on neuropsychological tests. Longitudinal studies indicate SMI as a risk factor or early sign of (AD). There is increasing evidence from neuroimaging that at the group level, subjects with SMI display evidence of AD related pathology. This study aimed to determine differences in cortical thickness between individuals with SMI and healthy control subjects (CO) using the FreeSurfer environment. 110 participants (41 SMI/69 CO) underwent structural 3D-T1 MR imaging. Cortical thickness values were compared between groups in predefined AD-related brain regions of the medial temporal lobe, namely the bilateral entorhinal cortex and bilateral parahippocampal cortex. Cortical thickness reduction was observed in the SMI group compared to controls in the left entorhinal cortex (p = 0.003). We interpret our findings as evidence of early AD-related brain changes in persons with SMI.

Richly detailed memories for particular events depend on processes that bind individual features of experience together. Previous cognitive behavioral research indicates that older adults have more difficulty than young adults in conditions requiring feature binding. We used functional magnetic resonance imaging (fMRI) during a working memory task to identify neural substrates of this age-related deficit in feature binding. For young, but not older, adults there was greater activation in left anterior hippocampus on combination trials (remember objects together with their locations) than on trials in which participants were told to remember only which objects or only which locations occurred. The results provide neuroimaging evidence for an age-related hippocampal dysfunction in feature binding in working memory.

Abstract An associative hypothesis to explain and predict older adults' deficient explicit episodic memory performance was outlined and tested. The hypothesis attributes a substantial part of older adults' deficient memory performance to their difficulty in merging unrelated attributes-units of an episode into a cohesive unit. Although each of the components can be memorized to a reasonable degree, the associations that tie the attributes-units to each other grow weaker in old age. Four experiments are reported that provide (a) a converging validity to the hypothesis by demonstrating this associative deficit for both interitem relationships and intraitem relationships and (b) a discriminant validity to the hypothesis by contrasting and testing competing predictions made by the associative hypothesis and by alternative hypotheses. The implications of these results to older adults' episodic memory performance are discussed.

The associative deficit hypothesis (M. Naveh-Benjamin, 2000) attributes age-related memory deficits to the inability to encode and retrieve bound units of information. The present experiment extended this deficit to a new form of stimuli, dynamic displays of people and their performance of everyday actions. Older and younger adults viewed a series of brief video clips, each showing a different person performing a different action, and were tested over memory for individual people, individual actions, and the person-action combinations. Older adults did exhibit an associative deficit, and this was related to an increased proportion of false alarms on the associative test.

Previous studies have indicated that memory training may help older people improve cognition. However, evidence regarding who will benefit from such memory trainings has not been fully discovered yet. Understanding the clinical and neural inter-individual differences for predicting cognitive improvement is important for maximizing the training efficacy of memory-training programs. The purpose of this study was to find the individual characteristics and brain morphological characteristics that predict cognitive improvement after a multi-strategic memory training based on metamemory concept. Among a total of 49 older adults, 39 participated in the memory-training program and 10 did not. All of them underwent brain MRIs at the entry of the training and received the neuropsychological tests twice, before and after the training. Stepwise regression analysis showed that lower years of education predicted cognitive improvement in the training group. In MRI, thinner cortices of precuneus, cuneus and posterior cingulate gyrus and higher white matter anisotropy of the splenium of corpus callosum predicted cognitive improvement in the training group. Old age, lower education level and individual differences in cortical thickness and white matter microstructure of the episodic memory network may predict outcomes following multi-strategic training.

Subjective cognitive decline (SCD) could indicate preclinical Alzheimer disease but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questionnaire versus consulting at a memory clinic. We compared 28 patients from a memory clinic with isolated SCD, 35 community-recruited elders with similarly high levels of self-reported cognitive difficulties and 35 community-recruited controls with low self-reported cognitive difficulties. Increased anxiety and 尾-amyloid deposition were observed in both groups with high self-reported difficulties while subclinical depression and (hippocampal) atrophy were specifically associated with medical help seeking. Cognitive tests showed no group differences. These results further validate the concept of SCD in both community and clinic-based groups. Yet, recruitment methods influence associated biomarkers and affective symptomatology, highlighting the heterogeneous nature of SCD depending on study characteristics.

OBJECTIVE: To study the relationship between subjective cognition and the neuropathological hallmark of Alzheimer disease (AD), amyloid-尾 (A尾) deposition, using carbon 11-labeled Pittsburgh Compound B (PiB) positron emission tomography in normal elderly individuals. DESIGN: Cross-sectional analysis. SUBJECTS: Forty-eight cognitively normal elderly subjects (11 with high PiB uptake and 28 with low PiB uptake) were included. All underwent clinical and neuropsychological evaluations, magnetic resonance imaging, and positron emission tomography. SETTING: Berkeley Aging Cohort Study. MAIN OUTCOME MEASURE: Relationship between PiB uptake and subjective cognition measures. RESULTS: Subjects with high PiB uptake showed significantly lower performance than those with low PiB uptake on an episodic memory measure and were less confident about their general memory abilities when required to evaluate themselves relative to other people of the same age. High and low PiB uptake groups did not differ on the accuracy of their cognitive self-reports compared with objective cognitive performance. General memory self-reports from the whole group were significantly correlated with regional PiB uptake in the right medial prefrontal cortex and anterior cingulate cortex and in the right precuneus and posterior cingulate cortex. Reduced confidence about memory abilities was associated with greater PiB uptake in these brain regions. All results were independent of demographic variables and depressive affects. CONCLUSIONS: A decrease of self-confidence about memory abilities in cognitively normal elderly subjects may be related to the neuropathological hallmark of AD measured with PiB-positron emission tomography. Subjective cognitive impairment may represent a very early clinical manifestation of AD.

Cognitive interventions for neurodegenerative diseases, such as Alzheimer's disease (AD), are best targeted at the preclinical stages, and subjective memory decline (SMD) without objective memory impairment on standard tests in older adults may represent a very early preclinical stage. Elaborated encoding effectively enhances memory performance for healthy older adults (HOAs), but has not been examined in people with SMD.To examine elaborated encoding in people with SMD, compared with HOAs.Participants were 32 HOAs and 22 people with SMD, defined using the Memory Complaint Questionnaire. Participants completed a verbal paired associate learning (PAL) task with delayed recall under elaborated and non-elaborated encoding conditions, as well as the California Verbal Learning Test-II.On the PAL learning trials, with age controlled, a significant interaction of group X encoding condition emerged, F(1, 51)66= 666.47, MSE66=666.54, p66=660.014, ηp266=660.11. Simple main effects revealed no differences between groups in the non-elaborated condition, but in the elaborated condition HOAs recalled more pairs than SMD, although both groups benefited from elaboration. At delayed recall, HOA recalled more pairs than SMD, F(1, 51)66= 664.59, p66=660.037, ηp266=660.08, and both groups benefited from elaboration, F(1, 52)66= 6619.25, p66< 660.001, ηp266=660.27.People with SMD benefit from elaborated encoding, although not to the same extent as HOAs. This objective difference in complex learning and memory suggests neural changes in SMD that may represent preclinical AD. Elaborated encoding is a promising technique to help maintain memory and decrease anxiety in this at-risk population.

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.

In this study functional magnetic resonance imaging (fMRI) is used to investigate the functional brain activation pattern in the preclinical stage of AD (pre-AD) subjects during a visual encoding memory task. Thirty subjects, eleven in the pre-AD stage, with decreased cerebrospinal fluid levels of A beta(42) (<500 pg/ml), and 19 controls with normal A beta(42) levels (CTR) were included. fMRI was acquired during a visual encoding task. Data were analyzed through an Independent Component Analysis (ICA) and region-of-interest-based univariate analysis of task-related BOLD signal change. From the ICA decomposition, we identified the main task-related component, which included the activation of visual associative areas and prefrontal executive regions, and the deactivation of the default-mode network. The activation was positively correlated with task performance in the CTR group (p < 0.0054). Within this pattern, subjects in the pre-AD stage had significantly greater activation of the precuneus and posterior cingulate cortex during encoding. Subjects in the pre-AD stage present distinct functional neural activity before the appearance of clinical symptomatology. These findings may represent that subtle changes in functional brain activity precede clinical and cognitive symptoms in the AD continuum. Present findings provide evidence suggesting that fMRI may be a suitable biomarker of preclinical AD.

At the present time, there is increasing recognition and understanding of the mild cognitive impairment (MCI) entity as a stage which is a frequent precursor and harbinger of subsequently manifest Alzheimer's disease (AD) and, perhaps, other related conditions, such as vascular dementia (Gauthieret al., 2006). MCI has been defined in two disparate but generally compatible ways in the current literature (see Reisberget al., 2008 (this issue), for a more complete historical overview of MCI). These two definitional approaches might be termed: (a) the clinical approach to MCI, and (b) the clinical plus psychometric approach to MCI.

Subjective cognitive impairment (SCI) in older persons without manifest symptomatology is a common condition with a largely unclear prognosis. We hypothesized that (1) examining outcome for a sufficient period by using conversion to mild cognitive impairment (MCI) or dementia would clarify SCI prognosis, and (2) with the aforementioned procedures, the prognosis of SCI subjects would differ significantly from that of demographically matched healthy subjects, free of SCI, termed no cognitive impairment (NCI) subjects. A consecutive series of healthy subjects, aged ≥40 years, presenting with NCI or SCI to a brain aging and dementia research center during a 14-year interval, were studied and followed up during an 18-year observation window. The study population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 ± 9.1 years, was well-educated (mean, 15.5 ± 2.7 years), and cognitively normal (Mini-Mental State Examination, 29.1 ± 1.2). A total of 213 subjects (81.9% of the study population) were followed up. Follow-up occurred during a mean period of 6.8 ± 3.4 years, and subjects had a mean of 2.9 ± 1.6 follow-up visits. Seven NCI (14.9%) and 90 SCI (54.2%) subjects declined ( P < .0001). Of NCI decliners, five declined to MCI and two to probable Alzheimer's disease. Of SCI decliners, 71 declined to MCI and 19 to dementia diagnoses. Controlling for baseline demographic variables and follow-up time, Weibull proportional hazards model revealed increased decline in SCI subjects (hazard ratio, 4.5; 95% confidence interval, 1.9–10.3), whereas the accelerated failure time model analysis with an underlying Weibull survival function showed that SCI subjects declined more rapidly, at 60% of the rate of NCI subjects (95% confidence interval, 0.45–0.80). Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI subjects ( P = .0003). These results indicate that SCI in subjects with normal cognition is a harbinger of further decline in most subjects during a 7-year mean follow-up interval. Relevance for community populations should be investigated, and prevention studies in this at-risk population should be explored.

The activation differences reported in this study may reflect the employment of compensatory strategies in the face of early AD pathology, although a number of alternative explanations need to be considered. Further studies with larger samples may help to determine whether the observed activation changes are likely to be associated with early neuropathological processes or with other unrelated factors. Copyright 2009 John Wiley & Sons, Ltd.

The objective was to examine whether subjective memory impairment (SMI) predicts all-cause dementia or Alzheimer's disease (AD) in a population-based study with long-term follow-up (median02=021002years). A total of 2043 initially dementia-free participants (≥ 6002years) made three memory ratings (“compared with others”, “compared with five years ago”, and “complaints from family/friends”) at baseline. During follow-up, 372 participants developed dementia (208 with AD). Cox regression revealed that subjective memory impairment ratings predicted all-cause dementia in models adjusting for age and sex (hazard ratio or HR from 2.04 to 3.94), with even higher values for AD (HR from 2.29 to 5.74). The result persisted in models including other covariates, including baseline episodic memory performance, and in analyses restricted to participants with long time to dementia diagnosis (≥ 502years). The findings underscore the usefulness of subjective memory assessment in combination with other factors in identifying individuals at risk for developing dementia.

<h2 class="secHeading" id="section_abstract">Abstract</h2><p id="simple-para0060">The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimer's Disease Neuroimaging Initiative (ADNI), performed ¹¹C-Pittsburgh Compound B (PiB) scans in 177 healthy controls (HC), 57 mild cognitive impairment (MCI) subjects, and 53 mild Alzheimer's disease (AD) patients. High PiB binding was present in 33% of HC (49% in ApoE-ε4 carriers vs 21% in noncarriers) and increased with age, most strongly in ε4 carriers. 18% of HC aged 60-69 had high PiB binding rising to 65% in those over 80 years. Subjective memory complaint was only associated with elevated PiB binding in ε4 carriers. There was no correlation with cognition in HC or MCI. PiB binding in AD was unrelated to age, hippocampal volume or memory. Beta-amyloid (Aβ) deposition seems almost inevitable with advanced age, amyloid burden is similar at all ages in AD, and secondary factors or downstream events appear to play a more direct role than total beta amyloid burden in hippocampal atrophy and cognitive decline.</p>

Background: Subjective memory impairment (SMI) is common among older adults. Increasing evidence suggests that SMI is a risk factor for future cognitive decline, as well as for mild cognitive impairment and dementia. Medial temporal lobe structures, including the hippocampus and entorhinal cortex, are affected in the early stages of Alzheimer's disease. The current study examined the gray matter (GM) volume and microstructural changes of hippocampal and entorhinal regions in individuals with SMI, compared with elderly control participants without memory complaints. Methods: A total of 45 participants (mean age: 70.31 6.07 years) took part in the study, including 18 participants with SMI and 27 elderly controls without memory complaints. We compared the GM volume and diffusion tensor imaging (DTI) measures in the hippocampal and entorhinal regions between SMI and control groups. Results: Individuals with SMI had lower entorhinal cortical volumes than control participants, but no differences in hippocampal volume were found between groups. In addition, SMI patients exhibited DTI changes (lower fractional anisotropy (FA) and higher mean diffusivity in SMI) in the hippocampal body and entorhinal white matter compared with controls. Combining entorhinal cortical volume and FA in the hippocampal body improved the accuracy of classification between SMI and control groups. Conclusions: These findings suggest that the entorhinal region exhibits macrostructural as well as microstructural changes in individuals with SMI, whereas the hippocampus exhibits only microstructural alterations.

To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects.[]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested.The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline.The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

Abstract Background: Subjective memory complaints (SMC) and depressive symptoms (SDS) are common in the elderly population. However, the relationship among SMC, SDS, and cognitive function remains unclear. We investigated these associations in the elderly from cognitively normal (CN), pre-mild cognitive impairment (MCI), and amnestic MCI (aMCI) groups. Methods: Participants (CN, 299; pre-MCI, 106; aMCI, 267) underwent comprehensive clinical and neuropsychological assessment. and self-report SMC and SDS questionnaires. SMC and SDS were administered in a self-report format. For each neuropsychological test z-score, stepwise multiple linear regressions were performed to assess the relative contribution of SMC, SDS, and their interactions. Results: SMC are associated with lower objective memory, while SDS are associated with lower psychomotor speed. Interactions between SMC and SDS were significant for tests of memory, executive function, psychomotor speed, and global cognition. Additional analyses revealed that SDS moderated the SMC-cognition relationship such that only individuals with higher SDS showed significant SMC-cognition associations. Limitations: Due to the cross-sectional design, associations among SMC, SDS, and cognitive function was rather weak, albeit significant. Additionally, future biomarker studies, such as those assessing amyloid burden, are needed to explore the mechanisms underlying the relationship among SMC, SDS, and cognitive function. Conclusion: Early identification of individuals at risk for developing abnormal cognitive changes is critical. Our findings from the study involving a large sample of carefully selected participants suggest that SMC and SDS could be used as early detection markers of Alzheimer's disease.

Cognitive neuroscience has made considerable progress in understanding the involvement of the medial temporal and frontal lobes in long-term memory. Whereas the medial temporal lobe has traditionally been associated with the encoding, storage and retrieval of long-term memories, the prefrontal cortex has been linked with cognitive control processes such as selection, engagement, monitoring and inhibition. However, there has been little attempt to understand how these regions might interact during encoding and retrieval, and little consideration of the anatomical connections between them. Recent advances in functional neuroimaging, neurophysiology, crossed-lesion neuropsychology and computational modeling highlight the importance of understanding how the medial temporal and frontal lobes interact to allow successful remembering, and provide an opportunity to explore these interactions.

PURPOSE: To prospectively determine whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer disease (AD) and its association with cognitive decline, and investigate the risk of progression to dementia in initially nondemented patients given baseline brain volume and whole-brain atrophy rate. MATERIALS AND METHODS: This study was IRB approved; written informed consent was obtained; and included 65 AD patients (38 women, 27 men; age, 52-81 years), 45 MCI patients (22 women, 23 men; age, 56-80 years), 27 patients with subjective complaints (12 women, 15 men; age, 50-87 years), and 10 healthy controls (six women, four men; age, 53-80 years). Two magnetic resonance (MR) images were acquired at average interval of 1.8 years +/- 0.7 (standard deviation). Baseline brain volume and whole-brain atrophy rates were measured on three-dimensional T1-weighted MR images (1.0 T; single slab, 168 sections; matrix size, 256 x 256; field of view, 250 mm; voxel size, 1 x 1 x 1.5 mm; repetition time msec/echo time msec/inversion time msec, 15/7/300; and flip angle, 15 degrees ). Associations were assessed by using partial-correlations. Cox proportional hazards models were used to estimate risk of developing dementia. RESULTS: Baseline brain volume was lowest in AD but did not differ significantly between MCI, subjective complaints, and control groups (P > .38). Whole-brain atrophy rates were higher in AD (-1.9% per year +/- 0.9) than MCI (-1.2% per year +/- 0.9, P = .003) patients, who had higher whole-brain atrophy rates than patients with subjective complaints (-0.7% per year +/- 0.7, P = .03) and controls (-0.5% per year +/- 0.5, P = .05). Whole-brain atrophy rate correlated with annualized Mini-Mental State Examination (MMSE) change (r = 0.48, P < .001), while baseline volume did not (r = 0.11, P = .22). Cox models showed that-after correction for age, sex, and baseline MMSE-a higher whole-brain atrophy rate was associated with an increased risk of pro

Abstract In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

Subjective cognitive decline (SCD) in otherwise normal aging may be identified via symptom inventories in a research setting ('questionnaire-discovered complaints') or via patients seeking evaluation/services in a clinical setting ('presenting complainers'). Most studies of SCD and amyloid-β (Aβ) imaging to date have used the former approach, with inconsistent results. To test whether 'presenting SCD' participants in an academic memory clinic setting show increased brain Aβ deposition on imaging. Fourteen patients (mean age 68.1, SD 4.0 years) diagnosed with subjective cognitive complaints with normal neuropsychological testing were recruited into a Pittsburgh compound B (PiB)-PET study. Detailed self-report inventories and additional cognitive tests were administered. Results were compared to a reference cohort of cognitively normal volunteers (NC) from an independent neuroimaging study (mean age 73.6, SD 5.8 years). 57% (8/14) of SCD participants were PiB-positive by a sensitive, regionally-based definition, compared to 31% (26/84) of the NC cohort. SCD participants had significantly higher PiB retention (SUVR) than NC in three of six regions of interest: frontal cortex (p66=660.02), lateral temporal cortex (p66=660.02), and parietal cortex (p66=660.04). SCD participants showed measurable deviations on questionnaires reflecting high negative affect (i.e., depressive symptoms and neuroticism). Findings were suggestive that deficits on verbal associative binding may be specific to Aβ-positive versus Aβ-negative SCD. Older participants with SCD presenting to a memory clinic in this pilot study sample have higher brain Aβ deposition compared to normal aging study volunteers unselected on complaints. Further study of presenting SCD are warranted to determine the prognostic significance of Aβ deposition in this context.

Subjective cognitive complaints in otherwise normal aging are common but may be associated with preclinical Alzheimer disease in some individuals. Little is known about who is mostly likely to show associations between cognitive complaints and preclinical Alzheimer pathology. We sought to demonstrate associations between subjective complaints and brain amyloid-β in cognitively normal older adults; and to explore personality factors as potential moderators of this association. Cross-sectional observational study. Clinical neuroimaging research center. Community volunteer sample of 92 healthy older adults, screened for normal cognition with comprehensive neuropsychological evaluation. Subjective cognitive self-report measures included the Memory Functioning Questionnaire (MFQ), Cognitive Failures Questionnaire, and the Subjective Cognitive Complaint Scale. Personality was measured with the NEO Five Factor Inventory. Brain amyloid-β deposition was assessed with Pittsburgh compound B (PiB)-PET imaging. One of three cognitive complaint measures, the MFQ, was associated with global PiB retention (standardized beta02=02610.230, p02= 0.046, adjusting for age, sex and depressive symptoms). Neuroticism moderated this association such that only high neuroticism individuals showed the predicted pattern of high complaint–high amyloid-β association. Evidence for association between subjective cognition and brain amyloid-β deposition in healthy older adults is demonstrable but measure-specific. Neuroticism may moderate the MFQ–amyloid-β association such that it is observed in the context of higher trait neuroticism. Subjective cognitive complaints and neuroticism may reflect a common susceptibility toward psychological distress and negative affect, which are in turn risk factors for cognitive decline in aging and incident Alzheimer disease.

Complaints about memory are common in older people but their relationship with underlying brain changes is controversial. To investigate the relationship between subjective memory impairment and previous or subsequent changes in white matter lesions and brain volumes. In a community cohort study of 1336 people without dementia, 4-year changes in brain magnetic resonance imaging measures were investigated as correlates of subjective memory impairment at baseline and follow-up. Subjective memory impairment at baseline was associated with subsequent change in hippocampal volume and at follow-up impairment was associated with previous change in hippocampal, cerebrospinal fluid and grey matter volume and with subcortical white matter lesion increases. All associations with volume changes were U-shaped with significant quadratic terms - associations between least decline and subjective memory impairment were potentially explained by lower baseline hippocampal volumes in the groups with least volume change. Associations between hippocampal volume change and subjective memory impairment at follow-up were independent of cognitive decline and depressive symptoms, they were stronger in participants with the apolipoprotein E (APOE) 4 allele and in those without baseline subjective memory impairment. Complaints of poor memory by older people, particularly when new, may be a realistic subjective appraisal of recent brain changes independent of observed cognitive decline.

Background/Aims: Subjective memory impairment (SMI) has been suggested as a manifestation of Alzheimer&#x2019;s Disease (AD) preceding mild cognitive impairment (MCI). In this study, we determined the volumes of the hippocampus, the entorhinal cortex (EC) and the amygdala to provide biological evidence for AD in SMI. Methods: Regional volumetric measures were manually traced on 3-Tesla MRI scans. Results: Total brain volume did not differ between the groups. Individuals with SMI had reduced volumes of the hippocampus bilaterally (right p = 0.001; left p &#x003C; 0.001), the bilateral EC (right p = 0.031, left p = 0.006) and the right amygdala (p = 0.01) compared to the control group. Conclusion: Volume reduction of bilateral hippocampus, bilateral EC and right amygdala supports the concept of SMI as a very early manifestation of AD prior to MCI. SMI may indicate awareness of a degenerative process that can still be functionally compensated.

Quantitative assessment of perceived memory functioning may be useful for screening older adults at risk for Alzheimer's disease. Individuals and their informants may provide complementary information relating to the anatomical distribution of tau.

research in cognitive psychology and neuropsychology of memory has produced a wealth of data that can be meaningfully ordered with the help of 2 general classes of concepts—memory processes and memory systems / proposes a simple model of organization of memory in which cognitive memory systems are related to one another in terms of the principal processes of encoding, storage, and retrieval / the central assumption of this SPI model—serial, parallel, independent—is that the relations among systems are process specific: information is encoded into systems serially, and encoding in 1 system is contingent on the successful processing of the information in another system; information is stored in different systems in parallel; and information from each system can be retrieved independently of information in other systems (PsycINFO Database Record (c) 2015 APA, all rights reserved)

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.

Abstract Objective: To identify the functional and pathologic correlates underlying subjective memory complaints (SMCs) in cognitively normal older adults. Methods: Two hundred fifty-one older adults underwent resting-state fluorodeoxyglucose (FDG)-PET and Pittsburg compound B-PET β-amyloid (Aβ) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on their Aβ burden. Age-adjusted voxel-wise correlations were used to examine SMCs, amyloid status (Aβ(+) vs Aβ(-)), and the interaction between SMCs and Aβ status as predictors of metabolism. Region-of-interest (ROI) analyses were performed to confirm the whole-brain analyses and to test for additional covariates. Results: Greater SMCs correlated with decreased FDG metabolism in the bilateral precuneus, bilateral inferior parietal lobes, right inferior temporal lobe, right medial frontal gyrus, and right orbitofrontal gyrus. A significant interaction effect between SMCs and amyloid burden was found such that Aβ(+) individuals with increased complaints had decreased FDG metabolism in the bilateral medial temporal lobes. ROI analyses confirmed the voxel-wise analyses result in that decreased precuneus metabolism was associated with greater SMCs regardless of Aβ status, age, or thickness, whereas the relationship between hippocampal metabolism and SMCs was a function of Aβ, even after adjustment for age, hippocampal volume, or depressive symptoms. Conclusions: These data show the relevant role of posterior and anterior midline regions in SMCs in older individuals. Decreased hippocampal metabolism may be a specific marker of subclinical changes in cognition due to amyloid pathology. However, longitudinal studies are needed to determine whether our findings foreshadow clinical decline.

A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in 鈥渄efault mode network previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.