Subjective memory complaints and cognitive impairment in older people

Subjective memory complaints (SMCs) are common in older people and are often thought to indicate cognitive impairment. We reviewed research on the relationship between SMCs and (a) current cognitive function, (b) risk of future cognitive decline, and (c) depression and personality. SMCs were found to be inconsistently related to current cognitive impairment but were more strongly related to risk of future cognitive decline. However, SMCs were consistently related to depression and some personality traits, e.g. neuroticism. In conclusion, the determinants of SMCs are complex. The utility of SMCs in the diagnosis of pre-dementia states (e.g. mild cognitive impairment) is uncertain and requires further evaluation.     

Safety of disclosing amyloid status in cognitively normal older adults

Introduction

Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk.

Amyloid burden accelerates white matter degradation in cognitively normal elderly individuals

Alterations in parietal and temporal white matter microstructure derived from diffusion tensor imaging occur in preclinical and clinical Alzheimer's disease. Amyloid beta (Aβ) deposition and such white matter alterations are two pathological hallmarks of Alzheimer's disease. However, the relationship between these pathologies is not yet understood, partly since conventional diffusion MRI methods cannot distinguish between cellular and extracellular processes. Thus, we studied Aβ‐associated longitudinal diffusion MRI changes in Aβ‐positive (N = 21) and Aβ‐negative (N = 51) cognitively normal elderly obtained from the Alzheimer's Disease Neuroimaging Initiative dataset using linear mixed models. Aβ‐positivity was based on Alzheimer's Disease Neuroimaging Initiative amyloid‐PET recommendations using a standardized uptake value ratio cut‐off of 1.11. We used free‐water imaging to distinguish cellular and extracellular changes. We found that Aβ‐positive subjects had increased baseline right uncinate fasciculus free‐water fraction (FW), associated with worse baseline Alzheimer's disease assessment scale scores. Furthermore, Aβ‐positive subjects showed faster decrease in fractional anisotropy (FW‐corrected) in the right uncinate fasciculus and faster age‐dependent right inferior longitudinal fasciculus FW increases over time. Right inferior longitudinal fasciculus FW increases were associated with greater memory decline. Importantly, these results remained significant after controlling for gray and white matter volume and hippocampal volume. This is the first study to illustrate the influence of Aβ burden on early longitudinal (in addition to baseline) white matter changes in cognitively normal elderly individuals at‐risk of Alzheimer's disease, thus underscoring the importance of longitudinal studies in assessing microstructural alterations in individuals at risk of Alzheimer's disease prior to symptoms onset.     

Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly.

OBJECTIVE: To investigate to what extent subjective memory complaints and APOE-epsilon4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects. METHODS: We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, > or =27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task-15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression. RESULTS: Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-epsilon4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-epsilon4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-epsilon4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors. CONCLUSIONS: Both memory complaints and APOE-epsilon4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-epsilon4 allele because they have an additional risk.     

Subcortical amyloid load is associated with shape and volume in cognitively normal individuals

Amyloid‐beta (Aβ) deposition is one of the main hallmarks of Alzheimer's disease. The study assessed the associations between cortical and subcortical ¹¹C‐Pittsburgh Compound B (PiB) retention, namely, in the hippocampus, amygdala, putamen, caudate, pallidum, and thalamus, and subcortical morphology in cognitively normal individuals. We recruited 104 cognitive normal individuals who underwent extensive neuropsychological assessment, PiB–positron emission tomography (PET) scan, and 3‐T magnetic resonance imaging (MRI) acquisition of T1‐weighted images. Global, cortical, and subcortical regional PiB retention values were derived from each scan and subcortical morphology analyses were performed to investigate vertex‐wise local surface and global volumes, including the hippocampal subfields volumes. We found that subcortical regional Aβ was associated with the surface of the hippocampus, thalamus, and pallidum, with changes being due to volume and shape. Hippocampal Aβ was marginally associated with volume of the whole hippocampus as well as with the CA1 subfield, subiculum, and molecular layer. Participants showing higher subcortical Aβ also showed worse cognitive performance and smaller hippocampal volumes. In contrast, global and cortical PiB uptake did not associate with any subcortical metrics. This study shows that subcortical Aβ is associated with subcortical surface morphology in cognitively normal individuals. This study highlights the importance of quantifying subcortical regional PiB retention values in these individuals.     

Subjective cognitive complaints versus objective neuropsychological performance in older adults with epilepsy

Memory complaints are common among older adults with epilepsy (OAE), though discrepancy between subjective complaints and objective performance often exists. This study examined how accurately OAE and their informants reported on the participant's cognitive difficulties by comparing ratings of everyday cognition to objective performance. Thirty-seven OAE and 27 older adult controls completed a brief battery of neuropsychological tests, the Beck Depression Inventory, and the Cognitive Difficulties Scale (CDS). Each participant had an informant who completed the CDS. Older adults with epilepsy performed worse than controls on cognitive testing and reported more subjective cognitive complaints. Neither participant- nor informant-reported cognitive complaints were related to performance on any of the neuropsychological tests for either the group with epilepsy or control group, but both were related to greater depressive symptoms. Results suggest that subjective report of cognitive problems by both OAE and their informants may not reliably reflect the extent to which these problems exist.     

Gender differences of neuropsychological profiles in cognitively normal older people without amyloid pathology

ObjectiveTo investigate the impact of sex on cognition among cognitively normal older people without amyloid pathology.MethodsThe study sample consisted of 83 males (mean age 74 years, ranging from 65 to 88 years) and 111 females (mean age 72 years, ranging from 65 to 89 years) who were cognitively normal without amyloid pathology confirmed by Pittsburgh compound B PET scan. We examined the sex discrepancies in cognition using a comprehensive neuropsychological battery.ResultsOur data showed significantly greater advantage for women than men on the tasks of verbal memory and category fluency while better performance of naming in men than women when age, education and depressive symptoms were considered.ConclusionThese findings highlight the importance of considering sex differences in the interpretation of cognitive data which contribute to clinical diagnosis of neurodegenerative disorders, such as Alzheimer's disease.     

Validation of the Face Name Associative Memory Exam in cognitively normal older individuals

The recently developed Face Name Associative Memory Exam (FNAME), a challenging paired associative learning task, shows promise in detecting the subtle cognitive changes characteristic of preclinical Alzheimer's disease. In this study, we evaluated the validity and reliability of the FNAME in 210 cognitively normal older individuals (58-90 years of age). Construct validity of the measure was assessed by principal components analysis, which revealed two independent factors. Correlations between the FNAME subtests and another episodic memory test were significant. The results indicated strong test-retest reliability in a subsample (n = 41). Normative data stratified by age were also generated.     

Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults

CNS inflammation is a key factor in Alzheimer’s Disease (AD), but its relation to pathological Aβ, tau, and APOE4 is poorly understood, particularly prior to the onset of cognitive symptoms. To better characterize early relationships between inflammation, APOE4, and AD pathology, we assessed correlations between cerebrospinal fluid (CSF) inflammatory markers and brain levels of Aβ and tau in cognitively normal older adults.Each participant received a lumbar puncture to collect and quantify CSF levels of TNFα, IL-6, IL-8, and IL-10, a T1-weighted MRI, and PET scanning with [¹⁸F]flortaucipir (FTP; n = 57), which binds to tau tangles and/or [¹⁸F]florbetapir (FBP; n = 58), which binds to Aβ. Parallel voxelwise regressions assessed relationships between each CSF inflammatory marker and FTP and FBP SUVR, as well as APOE4*CSF inflammation interactions.Unexpectedly, we detected significant negative associations between regional Aβ and tau PET uptake and CSF inflammatory markers. For Aβ PET, we detected negative associations with CSF IL-6 and IL-8 in regions known to show early accumulation of Aβ (i.e. lateral and medial frontal lobes). For tau PET, negative relationships were observed with CSF TNFα and IL-8, predominantly in regions known to exhibit early tau accumulation (i.e. medial temporal lobe). In subsequent analyses, significant interactions between APOE4 status and IL-8 on Aβ and tau PET levels were observed in spatially distinct regions from those showing CSF–Aβ/tau relationships.Results from the current cross-sectional study support previous findings that neuroinflammation may be protective against AD pathology at a given stage of the disease, and extend these findings to a cognitively normal aging population. This study provides new insight into a dynamic relationship between neuroinflammation and AD pathology and may have implications for whom and when neuroinflammatory therapies may be appropriate.     

Subjective memory complaints: presence, severity and future outcome in normal older subjects

BACKGROUND/AIMS: Subjective memory complaint (SMC) in normal individuals may predict future cognitive decline. The goal of this study was to examine whether the probability of decline increases with growing intensity of complaint. METHODS: Normal subjects over the age of 50 years were included in a longitudinal retrospective study (mean follow-up time = 8 years). All subjects (n = 230) underwent cognitive and medical examination at baseline. The presence of SMC was determined based on Global Deterioration Scale staging. A subgroup of 83 participants also received baseline assessment for the intensity of SMC. Logistic regression was used to predict outcome from baseline variables. Three outcome groups were established at the final visit: nondeclining, declining and diagnostically unstable (i.e. the diagnosis changed over time: from normal to mild cognitive impairment, then back to normal). RESULTS: The presence of SMC was a predictor of future decline but also increased the likelihood of the unstable diagnosis. Increasing intensity of SMC did not further raise the risk for decline. High intensity of complaints and more pronounced affective symptoms predicted the unstable clinical diagnosis. CONCLUSIONS: The presence of SMC contributes to the risk of future decline, however, the increasing intensity of the perceived impairment does not further enhance the risk.     

Subjective cognitive complaints in patients with Parkinson's disease

Mild cognitive impairment (MCI) is common in Parkinson's disease (PD), affecting almost all patients with PD at some time. It has been shown that patients with PD, who express subjective cognitive complaints, are at a higher risk of eventually developing PD‐MCI. This is corroborated by the Movement Disorders Society's (MDS) diagnostic criteria from 2012 for PD‐MCI, from which it follows that a subjective cognitive complaint must be present in addition to objective cognitive impairment for a patient with PD to receive a diagnosis of PD‐MCI. Nevertheless, there is currently no standardized measurement available for assessing subjective cognitive complaints. Therefore, this review aims to generate an overview of how subjective cognitive complaints are commonly operationalized in the empirical literature as well as whether they are found to be associated with the level of cognitive impairment. The findings revealed that a broad range of measures has been used to obtain subjective cognitive complaints and that there is little consistency between different studies with regard to how they have obtained these complaints, from whom they had obtained them, how many they have obtained, which types of complaints they have obtained and whether they were associated with cognitive impairment. Given the fact that the presence of subjective cognitive complaints is a requirement for setting a diagnosis, there is a need for more methodological consensus with regard to the measurement hereof.     

Subjective memory beliefs and cognitive performance in normal and mildly impaired older adults

Previous research suggests that subjective perceptions of memory may be related to objective memory performance. In the present study, healthy community-dwelling elders (N = 73, mean age = 75.25 years, education = 16.2 years) completed a neuropsychological assessment, including two questionnaires of subjective memory beliefs. Each participant was identified, via consensus conference, as belonging to either an amnestic mild cognitive impairment (MCI, n = 16) or no mild cognitive impairment (noMCI, n = 57) group. Results indicated that subjective memory capacity beliefs were significantly related to verbal memory performance in the MCI group, but not in the noMCI group. This differential relationship persisted even after controlling for depressive symptoms, and was not reflective of unequal variances in the two groups. Thus, results indicate that subjective memory beliefs may be better indicators of performance in those with possible incipient cognitive impairment than normal older adults, perhaps because persons with MCI have heightened insight into their memory functioning, and that this relationship is not due to group differences in depressive symptoms.     

Subjective ratings of cognitive and emotional functioning in patients with mild cognitive impairment and patients with subjective memory complaints but normal cognitive functioning

In a retrospective chart review, 39 patients referred for a clinical neuropsychological examination were identified as showing either mild cognitive impairment of the amnestic type (MCI-A; N = 21) or subjective memory complaints but with normal memory function (SMC; N = 18). During the clinical interview, patients and informants were routinely asked to make subjective ratings regarding the patient’s cognitive and affective functioning in everyday life. The purpose of this study was to determine whether these two patient groups (and their informants) significantly differed in their subjective reports about level of cognitive and affective difficulties. It was predicted that SMC patients would report higher levels of cognitive and emotional dysfunction than MCI-A patients. It was further predicted that MCI-A patients would underreport cognitive difficulties (compared to informant reports); SMC patients would demonstrate the opposite pattern. Results supported these predictions and suggest that routine assessment of subjective experiences of patients in conjunction with informant ratings may aid clinical diagnosis, particularly when the primary complaint is a decline in memory.     

Spatial pattern separation in cognitively normal young and older adults

This study examined the ability of cognitively normal young adults (n = 30) and older adults (n = 30) to perform a delayed match‐to‐sample task involving varying degrees of spatial interference to assess spatial pattern separation. Each trial consisted of a sample phase followed by a choice phase. During the sample phase, a circle appeared briefly on a computer screen. The participant was instructed to remember the location of the circle on the screen. During the choice phase, two circles were displayed simultaneously, and the participant was asked to indicate which circle was in the same location as the sample phase circle. The two circles on choice phase trials were separated by one of four possible spatial separations: 0, 0.5, 1.0, and 1.5 cm. Smaller separations are likely to create increased overlap among memory representations, which may result in heightened interference and a greater need for pattern separation. Consistent with this hypothesis, performance increased as a function of increased spatial separation in both young and older adults. However, young adults outperformed older adults, suggesting that spatial pattern separation may be less efficient in older adults due to potential age‐related changes in the dentate gyrus and CA3 hippocampal subregions. Older adults also were divided into older impaired and older unimpaired groups based on their performance on a standardized test of verbal memory. The older impaired group was significantly impaired relative to both the older unimpaired and young groups, suggesting that pattern separation deficits may be variable in older adults. The present findings may have important implications for designing behavioral interventions for older adults that structure daily living tasks to reduce interference, thus improving memory function. © 2012 Wiley Periodicals, Inc.