Genetic propensity for cerebral amyloidosis and risk of mild cognitive impairment and Alzheimer's disease within a cognitive reserve framework.

INTRODUCTION: We constructed a polygenic risk score (PRS) for ß-amyloid (PRSAß42) to proxy AD pathology and investigated its association with incident Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI) and the influence of cognitive reserve (CR), proxied by educational years, on the relationship between PRSAß42 and AD/aMCI risk. METHODS: A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSAß42 and CR with AD/aMCI incidence was examined with COX models. Then we examined the additive interaction between PRSAß42 and CR and the CR effect across participants with different PRSAß42 levels. RESULTS: Higher PRSAß42 and CR were associated with a 33.9% higher risk and 8.3% less risk for AD/aMCI, respectively. An additive interaction between PRSAß42 and CR was observed. High CR was associated with 62.6% less risk of AD/aMCI incidence only in the high-PRSAß42 group. DISCUSSION: A super-additive effect of PRSAß42 and CR on AD/aMCI risk was observed. CR influence was evident in participants with high PRSAß42.

The impact of COVID-19 pandemic on people with mild cognitive impairment/dementia and on their caregivers.

BACKGROUND: The novel coronavirus disease (COVID-19) was first detected in Mainland China in December 2019, and soon it spread throughout the world, with multiple physical and psychological consequences across the affected populations. AIMS: The aim of the current study was to analyze the impact of COVID-19 pandemic on older adults with mild cognitive impairment (MCI)/dementia and their caregivers as well. MATERIALS AND METHODS: Two hundred and four caregivers took part in the study, completing a self-reported questionnaire about the person with MCI/dementia and their own, since the lockdown period which started in February and ended in May of 2020 in Greece. RESULTS: Results indicated a significant overall decline of the people with MCI/dementia. Further, the domains in which people with MCI/dementia were mostly affected were: communication, mood, movement and compliance with the new measures. Caregivers also reported a great increase in their psychological and physical burden during this period, where the available support sources were limited. DISCUSSION: The pandemic threatens to disrupt the basic routines that promote mental and physical health of both people with MCI/dementia and t heir caregivers. CONCLUSION: Further measures to protect and provide support to people who suffer and their families are needed.

Dissociable cognitive patterns related to depression and anxiety in multiple sclerosis.

BACKGROUND: Individuals with multiple sclerosis (MS) frequently present with depression and anxiety, as well as cognitive impairment, challenging clinicians to disentangle interrelationships among these symptoms. OBJECTIVE: To identify cognitive functions associated with anxiety and depression in MS. METHODS: Mood and cognition were measured in 185 recently diagnosed patients (Reserve Against Disability in Early Multiple Sclerosis (RADIEMS) cohort), and an independent validation sample (MEM CONNECT cohort, n = 70). Partial correlations evaluated relationships of cognition to anxiety and depression controlling for age, sex, education, and premorbid verbal intelligence. RESULTS: In RADIEMS cohort, lower anxiety was associated with better nonverbal memory (rp = -0.220, p = 0.003) and lower depression to better attention/processing speed (rp = -0.241, p = 0.001). Consistently, in MEM CONNECT cohort, lower anxiety was associated with better nonverbal memory (rp = -0.271, p = 0.028) and lower depression to better attention/processing speed (rp = -0.367, p = 0.002). Relationships were unchanged after controlling for T2 lesion volume and fatigue. CONCLUSION: Consistent mood-cognition relationships were identified in two independent cohorts of MS patients, suggesting that cognitive correlates of anxiety and depression are separable. This dissociation may support more precise models to inform treatment development. Treatment of mood symptoms may mitigate effects on cognition and/or treatment of cognition may mitigate effects on mood.

Vitamin D intake is associated with dementia risk in the Washington Heights-Inwood Columbia Aging Project (WHICAP).

INTRODUCTION: Low vitamin D intake and low vitamin D circulating levels have been associated with increased risk for dementia. We aimed to examine the association between vitamin D intake and dementia in a multiethnic cohort. METHODS: A longitudinal study of 1759 non-demented older (≥65 years) participants of the Washington Heights-Inwood Columbia Aging Project with follow-up visits and completed a food frequency questionnaire. Dementia was diagnosed by consensus using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Cox hazard regression was performed. RESULTS: During a mean follow-up of 5.8 years, 329 participants developed dementia. Participants with the highest tertile of vitamin D intake from food sources had decreased risk (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.54-0.97, P = .030) for dementia compared with those with the lowest tertile, adjusting for age, sex, race/ethnicity, education, apolipoprotein E (APOE)-ε4, physical activity, Mediterranean diet (MeDI) score, income, depression, hypertension, diabetes, cardiovascular disease, and smoking. DISCUSSION: Higher vitamin D intake is associated with decreased risk of dementia in a multiethnic cohort.

Brain biomarkers and cognition across adulthood.

Understanding the associations between brain biomarkers (BMs) and cognition across age is of paramount importance. Five hundred and sixty-two participants (19-80 years old, 16 mean years of education) were studied. Data from structural T1, diffusion tensor imaging, fluid-attenuated inversion recovery, and resting-state functional magnetic resonance imaging scans combined with a neuropsychological evaluation were used. More specifically, the measures of cortical, entorhinal, and parahippocampal thickness, hippocampal and striatal volume, default-mode network and fronto-parietal control network, fractional anisotropy (FA), and white matter hyperintensity (WMH) were assessed. z-Scores for three cognitive domains measuring episodic memory, executive function, and speed of processing were computed. Multiple linear regressions and interaction effects between each of the BMs and age on cognition were examined. Adjustments were made for age, sex, education, intracranial volume, and then, further, for general cognition and motion. BMs were significantly associated with cognition. Across the adult lifespan, slow speed was associated with low striatal volume, low FA, and high WMH burden. Poor executive function was associated with low FA, while poor memory was associated with high WMH burden. After adjustments, results were significant for the associations: speed-FA and WMH, memory-entorhinal thickness. There was also a significant interaction between hippocampal volume and age in memory. In age-stratified analyses, the most significant associations for the young group occurred between FA and executive function, WMH, and memory, while for the old group, between entorhinal thickness and speed, and WMH and speed, executive function. Unique sets of BMs can explain variation in specific cognitive domains across adulthood. Such results provide essential information about the neurobiology of aging.

Sleep and subjective cognitive decline in cognitively healthy elderly: Results from two cohorts.

Subjective cognitive decline may reflect a dementia prodrome or modifiable risk factor such as sleep disturbance. What is the association between sleep and subjective cognitive decline? Cross-sectional design, from two studies of older adults: the WHICAP in the USA and the HELIAD in Greece. A total of 1,576 WHICAP and 1,456 HELIAD participants, without mild cognitive impairment, dementia or severe depression/anxiety, were included. Participants were mostly women, with 12 (WHICAP) and 8 (HELIAD) mean years of education. Sleep problems were estimated using the Sleep Scale from the Medical Outcomes Study. Subjective cognitive decline was assessed using a structured complaint questionnaire that queries for subjective memory and other cognitive symptoms. Multinomial or logistic regression models were used to examine whether sleep problems were associated with complaints about general cognition, memory, naming, orientation and calculations. Age, sex, education, sleep medication, use of medications affecting cognition, co-morbidities, depression and anxiety were used as co-variates. Objective cognition was also estimated by summarizing neuropsychological performance into composite z-scores. Sleep problems were associated with two or more complaints: WHICAP: ß = 1.93 (95% confidence interval: 1.59-2.34), p ≤ .0001; HELIAD: ß = 1.48 (95% confidence interval: 1.20-1.83), p ≤ .0001. Sleep problems were associated with complaints in all the cognitive subcategories, except orientation for the WHICAP. The associations were noted regardless of objective cognition. At any given level of objective cognition, sleep disturbance is accompanied by subjective cognitive impairment. The replicability in two ethnically, genetically and culturally different cohorts adds validity to our results. The results have implications for the correlates, and potential aetiology of subjective cognitive decline, which should be considered in the assessment and treatment of older adults with cognitive complaints.

Associations between sleep and obesity indices in older adults: results from the HELIAD study.

BACKGROUND: Short sleep duration and low sleep quality are negatively associated with obesity in young adults, but in older people the results are inconsistent. AIMS: The aim of the present study was to examine the associations between sleep duration and quality with both body mass index (BMI) and waist circumference (WC) and to investigate sex- and age-specific associations in a population-representative cohort of older adults. METHODS: 1781 participants ≥ 65 years old from the HELIAD study were included. Sleep duration and quality were based on self-report, whereas BMΙ and WC were evaluated clinically. RESULTS: Sleep duration was inversely related to WC, only in women, even after adjustment for age, sex, years of education, total energy intake and level of physical activity. Furthermore, sleep quality was negatively related to both BMI and WC in women. In men, however, no significant relationships were observed between these variables. Associations between sleep and weight did not differ between those aged < 73 and ≥ 73 years old. DISCUSSION: To the best of our knowledge, this is the first study examining both sleep duration and quality with BMI and WC in older adults, performing by-sex analysis. Although additional studies are needed, improvements in sleep habits should be considered in weight management of older individuals. CONCLUSIONS: Our results suggest that poor sleep is associated to adverse weight effects in older women, but not men.

Older adults with poor self-rated memory have less depressive symptoms and better memory performance when perceived self-efficacy is high.

OBJECTIVE: To investigate whether self-efficacy moderates the association between self-rated memory and depressive symptoms in a large sample of older adults. The influence of self-efficacy and depressive symptoms on memory performance was also examined in a subsample of individuals who reported poor memory. METHODS: Non-demented participants (n = 3766) were selected from the 2012 wave of the Health and Retirement Study. Depressive symptomatology was assessed with the 8-item Center for Epidemiologic Studies Depression Scale. A modified version of the Midlife Developmental Inventory Questionnaire was used as the measure of self-efficacy. Participants were asked to rate their memory presently on a five-point scale from Excellent (1) to Poor (5). Immediate memory and delayed memory (after a 5-min interval) were measured by the number of correct words recalled from a 10-item word list. RESULTS: Multiple regression analyses revealed that negative ratings of memory were significantly associated with greater levels of depressive symptoms, with this effect being greatest in those with low levels of self-efficacy. Additionally, greater self-efficacy was associated with optimal objective memory performances but only when depressive symptoms were low in individuals who reported poor memory function (n = 1196). CONCLUSION: Self-efficacy moderates the relationship between self-rated memory function and depressive symptoms. Higher self-efficacy may buffer against the impact of subjective memory difficulty on one's mood and thereby mitigating the effect of depressive symptoms on memory. Interventions should focus on increasing perceived self-efficacy in older adults reporting poor memory function to potentially minimize memory impairment.

Daytime somnolence as an early sign of cognitive decline in a community-based study of older people.

OBJECTIVE: This study aimed to examine the association between self-reported sleep problems and cognitive decline in community-dwelling older people. We hypothesized that daytime somnolence predicts subsequent cognitive decline. METHODS: This is a longitudinal study in a 3.2-year follow-up, with 18-month intervals. The setting is the Washington Heights-Inwood Community Aging Project. There were 1098 participants, who were over 65 years old and recruited from the community. Sleep problems were estimated using five sleep categories derived from the RAND Medical Outcome Study Sleep Scale: sleep disturbance, snoring, awaken short of breath/with a headache, sleep adequacy, and daytime somnolence. Four distinct cognitive composite scores were calculated: memory, language, speed of processing, and executive functioning. We used generalized estimating equations analyses with cognitive scores as the outcome, and time, sleep categories and their interactions as the main predictors. Models were initially unadjusted and then adjusted for age, gender, education, ethnicity, depression, and apolipoprotein E-ε4 genotype. RESULTS: Increased daytime somnolence (including feeling drowsy/sleepy, having trouble staying awake, and taking naps during the day) was linked to slower speed of processing both cross-sectionally (B = -0.143, p = 0.047) and longitudinally (B = -0.003, p = 0.027). After excluding the demented participants at baseline, the results remained significant (B = -0.003, p = 0.021). CONCLUSIONS: Our findings suggest that daytime somnolence may be an early sign of cognitive decline in the older population.

Self-Reported Sleep Disordered Breathing as Risk Factor for Mortality in the Elderly.

BACKGROUND: This study aimed to examine the association between self-reported sleep disordered breathing (SDB) ("awaken short of breath or with a headache") and mortality in a large and ethnically diverse group of community-dwelling elderly people. METHODS: A total of 1288 participants, 65 years and older, were examined longitudinally. Sleep problems were estimated using the Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, awaken short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and mortality. Age, gender, education, ethnicity, and body mass index were included as covariates. In further analyses we included hypertension, diabetes, heart disease, and stroke as additional covariates. RESULTS: The participants were followed for up to 6 years (mean = 2.9, standard deviation = 1.1), and 239 (18.6%) participants died during the follow-up. In unadjusted models, SDB at the initial visit was associated with mortality (hazard ratio [HR] = 1.37; 95% confidence interval [CI] 1.21-1.55; P < .0001). After adjusting for all the covariates, the relationship between SDB and mortality remained significant (HR = 1.48; 95% CI 1.29-1.70; P < .0001). Participants with Caribbean-Hispanic ancestry have higher risk for mortality. CONCLUSIONS: Our results suggest that SDB is a risk factor for mortality in a large and ethnically diverse group of older adults, independent of demographic and clinical factors. Further research is needed to examine the underlying mechanisms of this association.

Sleep problems as predictors of cognitive decline in essential tremor: A prospective longitudinal cohort study.

BACKGROUND: There is growing evidence that essential tremor (ET) patients are at high risk of cognitive impairment. Predictors of cognitive impairment have not been studied extensively. There is evidence from cross-sectional studies that sleep dysregulation is associated with cognitive dysfunction in ET, but longitudinal studies of the impact of sleep disruption on cognitive change have not been conducted. We investigated the extent to which sleep problems predict cognitive change in patients with ET. METHODS: ET cases enrolled in a prospective, longitudinal study of cognitive performance. Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Cognitive abilities across five domains (memory, executive function, attention, language, and visuospatial ability), and a global cognitive score (mean of the domains) were extracted from an extensive neuropsychological assessment. Generalized estimated equations were used to examine the association between baseline sleep problems and cognitive changes over three follow-up assessments each spaced 18 months apart. RESULTS: The 188 non-demented ET cases had a mean age of 77.7 ± 9.5 years. Longer sleep latency was associated with longitudinal decline in executive function (p = 0.038), and marginally with longitudinal decline in global cognitive performance (p = 0.075). After excluding 29 cases with mild cognitive impairment, results were similar. CONCLUSION: Cognitively healthy people with ET who have longer sleep latency had greater declines in executive function during prospective follow-up. Early detection of, and possibly intervention for, abnormal sleep latency may protect against certain aspects of cognitive decline in ET patients.

Long COVID-19 Symptoms in People with Dementia or Mild Cognitive Impairment.

What is the impact of long COVID-19 on people with mild cognitive impairment (MCI) or dementia? Self-reported questionnaire was used for the report of long COVID-19 symptoms. People with MCI or dementia or their caregivers regarding patients' health were recruited COVID-19 throughout from the Athens Alzheimer's Association. We included 72 participants. Thirty had the diagnosis of MCI and 39 had dementia. Most symptoms lasted for 3-4 weeks. The majority of patients reported having all the symptoms, with fatigue being the major disturbance. The diagnosis and the management of long COVID-19 symptoms requires a more holistic and comprehensive approach.

Association of Cognitive Polygenic Index and Cognitive Performance with Age in Cognitively Healthy Adults.

Genome-wide association studies have discovered common genetic variants associated with cognitive performance. Polygenic scores that summarize these discoveries explain up to 10% of the variance in cognitive test performance in samples of adults. However, the role these genetics play in cognitive aging is not well understood. We analyzed data from 168 cognitively healthy participants aged 23-77 years old, with data on genetics, neuropsychological assessment, and brain-imaging measurements from two large ongoing studies, the Reference Abilities Neural Networks, and the Cognitive Reserve study. We tested whether a polygenic index previously related to cognition (Cog PGI) would moderate the relationship between age and measurements of the cognitive domains extracted from a neuropsychological evaluation: fluid reasoning, memory, vocabulary, and speed of processing. We further explored the relationship of Cog PGI and age on cognition using Johnson-Neyman intervals for two-way interactions. Sex, education, and brain measures of cortical thickness, total gray matter volume, and white matter hyperintensity were considered covariates. The analysis controlled for population structure-ancestry. There was a significant interaction effect of Cog PGI on the association between age and the domains of memory (Standardized coefficient = -0.158, p-value = 0.022), fluid reasoning (Standardized coefficient = -0.146, p-value = 0.020), and vocabulary (Standardized coefficient = -0.191, p-value = 0.001). Higher PGI strengthened the negative relationship between age and the domains of memory and fluid reasoning while PGI weakened the positive relationship between age and vocabulary. Based on the Johnson-Neyman intervals, Cog PGI was significantly associated with domains of memory, reasoning, and vocabulary for younger adults. There is a significant moderation effect of genetic predisposition for cognition for the association between age and cognitive performance. Genetics discovered in genome-wide association studies of cognitive performance show a stronger association in young and midlife older adults.

The Effect of Prolonged Lockdown Due to COVID-19 on Greek Demented Patients of Different Stages and on Their Caregivers.

BACKGROUND: The impact of the new coronavirus disease (COVID-19) is deteriorating as time passes and the virus keeps spreading, with people with dementia and their caregivers being affected significantly. OBJECTIVE: The aim of this study was to examine the effect of prolonged isolation because of the COVID-19 pandemic on people with dementia and their caregivers. METHODS: Caregivers answered online questions regarding their own physical and psychological burden, and of the person they take care of. Participants were mostly members of online seminars of the Athens Alzheimer's Association. Questions referred to their own burden, the overall decline of the persons they take care of, and changes in specific domains as well. Further, participants were asked about any changes between the two major lockdown periods. Analysis was performed including the total sample and then, by three different stages of dementia. RESULTS: A total of 339 caregivers took part in the study. Results indicated significant decline, both in an overall aspect of the people with dementia, and in specific domains (mostly communication and mood). Regarding the caregivers, they reported having significantly increased physical and psychological burden, and also, noticing an overall change between the two lockdown periods in their own burden. Analysis by dementia-stage group indicated that significant decline occurred both in the middle-stage and the late-stage group. CONCLUSION: An urgency for further support of both the people with neurodegenerative disorders and their caregivers is needed. Collaboration among care workers, online programs, governmental support, and day-care centers should be planned to ensure continuity of care for those in need during the pandemic.

Sleep Polygenic Risk Score Is Associated with Cognitive Changes over Time.

Sleep problems have been associated with cognition, both cross-sectionally and longitudinally. Specific genes have been also associated with both sleep regulation and cognition. In a large group of older non-demented adults, we aimed to (a) validate the association between Sleep Polygenic Risk Score (Sleep PRS) and self-reported sleep duration, and (b) examine the association between Sleep PRS and cognitive changes in a three-year follow-up. Participants were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A structured, in-person interview, consisting of a medical history report and physical examination, was conducted for each participant during each of the visits (baseline and first follow-up). In total, 1376 participants were included, having all demographic, genetic, and cognitive data, out of which, 688 had at least one follow-up visit. In addition, an extensive neuropsychological assessment examining five cognitive domains (memory, visuo-spatial ability, attention/speed of processing, executive function, and language) was administered. A PRS for sleep duration was created based on previously published, genome-wide association study meta-analysis results. In order to assess the relationship between the Sleep PRS and the rate of cognitive change, we used generalized estimating equations analyses. Age, sex, education, ApolipoproteinE-ε4 genotype status, and specific principal components were used as covariates. On a further analysis, sleep medication was used as a further covariate. Results validated the association between Sleep PRS and self-reported sleep duration (B = 1.173, E-6, p = 0.001). Further, in the longitudinal analyses, significant associations were indicated between increased Sleep PRS and decreased visuo-spatial ability trajectories, in both the unadjusted (B = -1305.220, p = 0.018) and the adjusted for the covariates model (B = -1273.59, p = 0.031). Similarly, after adding sleep medication as a covariate (B = -1372.46, p = 0.019), none of the associations between Sleep PRS and the remaining cognitive domains were significant. PRS indicating longer sleep duration was associated with differential rates of cognitive decline over time in a group of non-demented older adults. Common genetic variants may influence the association between sleep duration and healthy aging/cognitive health.

Association Between Sleep Disturbances and Frailty: Evidence From a Population-Based Study.

OBJECTIVE: To explore the association between both self-reported quality and quantity sleep characteristics and frailty status in a large non-sex-specific population of older individuals in Greece. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: In total, 1984 older individuals (≥65 years old) were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). MEASURES: Frailty was assessed using 3 different definitions, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI), and the Groningen Frailty Indicator (GFI). Sleep quality was evaluated through the Sleep Index II, which includes 9 of the 12 self-reported items of the Medical Outcomes Study-Sleep Scale. To examine sleep duration, participants were asked to report on how many hours they slept each night during the past 4 weeks. Logistic regression models adjusted for multiple covariates were explored. Additional analyses, stratified by gender, adjusting for sleep-related medications and excluding participants diagnosed with dementia, were also performed. RESULTS: In total, 389 (20%), 619 (31.9%), and 608 (31.3%) participants were categorized as frail according to the FI, the TFI, and the GFI respectively. Sleep quality was significantly associated with frailty in all models. Even after adjusting for subjective sleep duration, compared with participants who subjectively reported high sleep quality, those with low sleep quality had 3.7, 2.6, and 2.5 more times to be frail as measured with FI, TFI, and GFI respectively. Regarding the associations between frailty and self-reported sleep duration, sex-specific associations were observed: prolonged sleep duration was associated with frailty in the subsample of male participants. CONCLUSIONS AND IMPLICATIONS: The present study shows a strong correlation between subjective sleep quality and frailty status, contributing substantial information to the growing literature demonstrating that sleep is associated with older people's overall health. Sleep complaints should not be underestimated, and older individuals who self-report sleep disorders should be further assessed for frailty.

Sleep and the aging brain. A multifaceted approach.

In the current review we provide a theoretical background on studies examining the association between sleep and brain function. We focus on the association between sleep and cognitive performance, cognitive changes over time and incident dementia as well. We then present some data on the link between sleep and subjective cognitive complaints, in participants without any objective clinical cognitive decline. We conclude with investigating the association between sleep and brain biomarkers, by highlighting the importance of specific genes and specific brain regions' morphometry. The role of sleep is vital in maintaining a healthy aging brain, and multiple factors should be taken under account when investigating this association.

Optimized prediction of cognition based on brain morphometry across the adult life span.

We mapped out the combined and unique contributions of 5 different biomarkers for 2 cognitive outcomes in cognitively healthy adults. Beside associations of biomarkers with cognition in the full experimental sample, we focused on how well any such associations would persist in held-out data. Three hundred thirty-five cognitively normal participants, 20-80 years older, were included in the study. Z-scores were computed for fluid reasoning and vocabulary. The following imaging data were included: regional brain volume, regional thickness, fractional anisotropy of white-matter tracts, volumes of select deep gray-matter regions, and global white-matter hyperintensity. Volume accounted for most of the variance in both cognitive domains. In out-of-sample data, fluid reasoning was best predicted by volumes, but vocabulary by the combination of all modalities. Although the predictive utility was better overall for older participants, the information gleaned relative to null models was less for older participants. An optimized set of brain biomarkers can thus predict cognition in out-of-sample data, to various degrees, for both fluid and crystallized intelligence.

When time's arrow doesn't bend: APOE-ε4 influences episodic memory before old age.

Episodic memory impairment is the hallmark symptom of Alzheimer's Disease (AD). However, episodic memory has also been shown to decline across the lifespan. Here, we investigated whether episodic memory is differentially affected relative to other cognitive abilities before old age, and whether being an Apolipoprotein E (APOE) ε4 carrier -a genetic risk factor for developing AD-exacerbates any such impairments. We used general linear models to test for performance differences within 4 composite measures of cognition - episodic memory, semantic memory, speed of processing, and fluid reasoning-- as a function of age group (young, Mage = 30.21 vs. middle-aged, Mage = 50.84) and APOE-ε4 genotype status (ε4+ vs. ε4-). We replicated findings of age-related reductions in episodic memory, speed of processing, and fluid reasoning, and age-related increases in semantic memory. However, we also found that APOE genotype status moderated the age-related declines in episodic memory: APOE-ε4+ middle-aged adults exhibited impairments relative to both APOE-ε4- middle-aged participants, and APOE-ε4+ younger adults. These results suggest specific and dynamic alterations to episodic memory as a function of APOE allelic variation and age.

Regional cortical thickness and neuroticism across the lifespan.

Neuroticism is associated with greater reactivity to stress and lifetime psychopathology. In the present study we examined the association between neuroticism and regional and total cortical thickness (CT) across the lifespan, accounting for gender. We also assessed interactions among these factors. 450 subjects between 19 and 80 years were included. Participants completed the International Personality Item Pool and a structural MRI scan. Total CT and the mean values of CT in five regions of interest were examined. We also investigated the interaction effect among age, gender and neuroticism on CT. There was no significant association between neuroticism and regional/total CT. A significant interaction between neuroticism, age, and gender on the thickness of the anterior cingulate was found. Women high in neuroticism showed a thinner anterior cingulate cortex than women low in neuroticism, with increasing age. In contrast, men high in neuroticism had a thicker anterior cingulate cortex compared to men low in neuroticism, with increasing age. Overall, high neuroticism was associated with differential cortical thickness in the anterior cingulate among men and women with increasing age.