Monongahela-Youghiogheny Healthy Aging Team Research Articles

Marijuana use among community-dwelling older adults: A population-based study.

There is a paucity of population-level data on marijuana use and mental health and functioning in older adults. We analyzed cross-sectional data (n=910) from a well-characterized cohort, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. MYHAT is an age-stratified random sample of the population age 65years and older from a small-town in the USA. Half the sample was female and half were over 75 (Mean age=77). Most participants were non-Hispanic White. Marijuana use was assessed by self-report and symptoms of mood disorders were screened using the modified Centers for Epidemiological Studies-Depression Scale and the Generalized Anxiety Disorder screener. Cognition was assessed by the Mini-Mental State Examination and a neuropsychological test battery; functioning using the OARS Activities of Daily Living and Instrumental Activities of Daily Living; and overall assessment using the Clinical Dementia Rating (CDR®). One in five MYHAT participants had a history of marijuana use and 5% reported recent use, primarily for pain (41%) and recreation/relaxation (37%). Recent use was associated with cigarette and alcohol use, symptoms of depression or anxiety, and impairments in attention. Twenty-percent of community-dwelling older adults living in a US state where recreational marijuana use is illegal had a history of marijuana use. Recent marijuana use was less common but, consistent with prior research, associated with other substance use and poorer mental health.

FC9: Ethno-racial identity and cognitive impairment: A population-based study

Objective:Health disparities between communities with greater and lesser advantages are a global concern. In the USA, self-identified race as African American (AA) is consistently associated with mild cognitive impairment (MCI) and dementia, compared to Americans of European descent. In a prospective population-based study, we sought to confirm this association and investigate potential explanatory factors.Methods:The Monongahela-Youghiogheny Healthy Aging Team (MYHAT) and Seniors Project 15104 (SP15104) studies recruited adults aged 65+ years from a group of small towns of lower socioeconomic status in the US. MYHAT recruited by age-stratified random sampling from the voter registration list for all towns; SP15104 recruited by intensive community engagement from three towns with populations that are 60% AA. Based on the Clinical Dementia Rating (CDR), MCI was defined as CDR=0.5 and dementia as CDR > 1. Using Cox proportional hazard models, we modeled time to incident CDR > 0.5 from baseline as a function of race (AA vs. all other), other demographics, and several other covariates at baseline.Results:The sample of 2120 individuals was 8% AA, and 62% female, with median age of 73y, and median educational level of partial college. During follow up of up to 14.5 years, 499 participants developed new-onset MCI/dementia (CDR >0.5). Cox models revealed that being AA was significantly associated with incident CDR > 0.5 (HR=1.45. 95% CI:1.01,2.10). Inclusion of age, sex, and education in the model increased the HR for race to 1.63 (1.1, 2.3). Adding number of regularly taken prescription drugs (reflecting overall morbidity), depression symptoms, preceding year alcohol consumption, and number of visits to emergency or urgent care together reduced the HR to 1.4 (0.96, 2.0), no longer statistically significantConclusions:In this population-based cohort study, self-identified African Americans had an about 40% elevated risk of developing MCI/dementia. Adjusting for demographics, the significant association between race and incident MCI/dementia was attenuated by variables reflecting depression, greater general morbidity, and lesser access to regular health services. These variables possibly reflect downstream effects of historic discrimination, but couldstill be modifiable risk factors for MCI/dementia. Addressing them could potentially mitigate ethno-racial disparities in cognitive impairment.

Social Isolation and Loneliness in a Population Study of Cognitive Impairment: The MYHAT Study.

In this study, we examined associations of social isolation and loneliness with cognitive impairment among older adults from a Rust Belt region in Southwest Pennsylvania. We used data from the population-based Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. We found that (a) 11 items combined into two reliable composites of social isolation and loneliness; (b) unique to this study, providing unpaid help to others was an indicator of reduced social isolation; (c) social isolation and loneliness were positively associated with cognitive impairment; and (d) these associations were appreciably attenuated by general health and physical functional status and depressive symptoms, respectively. We concluded that social isolation and loneliness are differentially associated with older adults' cognitive health, and that their effects might operate through separate pathways. Approaches to address social isolation and loneliness should consider the community context and its implications for older adults' cognitive health.

Plasma biomarkers identify older adults at risk of Alzheimer's disease and related dementias in a real-world population-based cohort.

Plasma biomarkers-cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)-have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, independently of brain and cerebrospinal fluid biomarkers. We measured plasma phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (Aβ)42/40 ratio in 847 participants from a population-based cohort in southwestern Pennsylvania. K-medoids clustering identified two distinct plasma Aβ42/40 modes, further categorizable into three biomarker profile groups: normal, uncertain, and abnormal. In different groups, plasma p-tau181, NfL, and GFAP were inversely correlated with Aβ42/40, Clinical Dementia Rating, and memory composite score, with the strongest associations in the abnormal group. Abnormal plasma Aβ42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher ADRD biomarker levels, with potential implications for population screening. Population-based plasma biomarker studies are lacking, particularly in cohorts without cerebrospinal fluid or neuroimaging data. In the Monongahela-Youghiogheny Healthy Aging Team study (n=847), plasma biomarkers associated with worse memory and Clinical Dementia Rating (CDR), apolipoprotein E ε4, and greater age. Plasma amyloid beta (Aβ)42/40 ratio levels allowed clustering participants into abnormal, uncertain, and normal groups. Plasma Aβ42/40 correlated differently with neurofilament light chain, glial fibrillary acidic protein, phosphorylated tau181, memory composite, and CDR in each group. Plasma biomarkers can enable relatively affordable and non-invasive community screening for evidence of Alzheimer's disease and related disorders pathophysiology.

Meta‐analysis of age‐related cognitive decline reveals a novel locus for the attention domain and implicates a COVID‐19 related gene for global cognitive function

AbstractBackgroundCognition is a highly complex polygenic trait. A limited number of studies have explored the genetic basis of cognitive decline in aging populations using cognitive domain specific measures.MethodTo identify genetic markers for cognitive decline, we conducted a genome‐wide association meta‐analysis and gene‐based tests on five different cognitive domains (attention, language, executive function, visuospatial abilities, memory) and global cognition on 3,068 older individuals (≥65 years) of European ancestry derived from three prospective cohorts: Gingko Evaluation Memory Study (GEMS), Monongahela‐Youghiogheny Healthy Aging Team (MYHAT) and Monongahela Valley Independent Elders Survey (MoVIES). All subjects completed a comprehensive neuropsychological battery of tests covering the examined domains. A linear mixed effects model was used to estimate the longitudinal decline in cognitive scores after adjusting for sex, baseline age and education. Global cognitive decline was defined as a decline in average performance in neuropsychological tests across the five domains.ResultGenome‐wide significant association of APOE*4 was observed with decline in the memory domain (p= 8.93E‐09) and global cognitive function (p= 2.69E‐08).We identified a novel locus for decline in the attention domain on chromosome 9 in an intergenic region between RASEF/FRMD3 (p = 3.17E‐08). Gene‐based analysis identified TMPRSS11D as the top gene for decline in global cognition (Bonferroni corrected p= 2.48E‐06). TMPRSS11D plays a role in host‐defense system and recent studies have shown that it activates spike protein of SARS‐CoV‐2 and facilitates viral entry to cell (Viruses 2021;13:384; J Biol Chem 2021; 296:100135).ConclusionWe have identified a novel locus for longitudinal decline in the attention domain, replicated the association of APOE*4 with the global and memory domains, and potentially implicated the role of TMPRS11D in cognitive decline through gene‐based analysis. The association of TMPRSS11D with cognitive decline might help to explain cognitive impairment observed in some patients after COVID‐19 infection (Br J Anaesth 2021; 25:e54; JAMA Netw Open 2021; 4(10):e2130645 ). While functional studies might help to understand the underlying molecular mechanism of the associated loci, cognitive decline studies with larger samples are essential to establish these findings.

Genome‐wide meta‐analysis of age‐related cognitive decline in population‐based older individuals

AbstractBackgroundCognitive decline is a major characteristic of aging and neurogenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease and other dementias. With worldwide increases in life‐expectancy and elderly population, cognitive decline is a major public health concern. Understanding genetic contributors to age‐related decline in cognition may facilitate identification of the molecular mechanisms of cognitive decline.MethodTo discover genetic influences on cognitive decline, we conducted genome‐wide meta‐analyses on longitudinal performance of five cognitive domains (attention, language, executive function, visuospatial, memory) and the global domain, constructed from five domains, using 3068 individuals aged 65 and above across three longitudinal cohorts: the Gingko biloba Memory Evaluation Study (GEMS), Monongahela‐Youghiogheny Healthy Aging Team (MYHAT) and Monongahela Valley Independent Elders Survey (MoVIES). A linear mixed effect model was used to find individual specific slopes by adjusting for baseline age, years of education and sex.Results APOE*4 (rs429358), a well‐known risk factor for AD, demonstrated a genome‐wide significant association with the memory (P= 1.37E‐09) and global (P= 9.26E‐10) domains. Previous studies have also reported APOE*4 ‘s association with memory decline. In addition to APOE*4, multiple suggestive associations of gene loci with cognition were also observed for each domain as follows: attention on chromosome 9 near RASEF/FRMD3 (P = 8.29E‐08), memory on chromosome 6 near ID4/MBOAT1(P = 1.27E‐07), visuospatial function on chromosome 11 near PAMR (P = 2.74E‐07), language on chromosome 9 near PSAT1 (P = 4.08E‐07), executive function on chromosome 4 near SNHG27 (P = 6.49E‐07), and global function on chromosome 4 near LINC00290 (P=8.80E‐07).ConclusionOur result suggests that in addition to APOE, multiple genetic loci affect cognitive decline in older individuals. These findings may offer new insights into understanding the genetic architecture of cognitive decline.

Reading the Mind in the Eyes: A Population-Based Study of Social Cognition in Older Adults

<h3>Introduction</h3> Social cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. It is increasingly recognized in neurocognitive disorders, and it is included in DSM-5 as one of the six core cognitive domains to be assessed for the diagnosis of neurocognitive disorders. However, unlike other cognitive domains, social cognition is not routinely measured in geriatric evaluations. The Reading the Mind in the Eyes Test [RMET] is a measure of individual differences in "Theory of Mind (ToM)", the most representative mechanism of social cognition, which forms the basis of empathy. The present study aims a) to describe the distribution of the RMET scores in a population-based sample of older adults using a 10-item version of the RMET [RMET-10], b) to describe population-based norms of RMET-10, and c) to examine its associations with demographics, literacy, cognitive screen, clinical dementia rating, cognitive domains derived from a neuropsychiatric battery, anxiety and depression screens, and a test of social norms recognition. <h3>Methods</h3> Participants Participants were from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study which is focused on the epidemiology of mild cognitive impairment and dementia. The MYHAT cohort was accrued by age-stratified random selection from the voter registration in small-town communities in Pennsylvania, USA. Individuals were excluded if they were too ill to participate, had vision or hearing impairment, had decisional incapacity, or had substantial cognitive impairment (MMSE scores <21). RMET-10 is an abbreviated version of the full RMET, an advanced test of ToM. The test stimuli consist of 10 grey-scale photos of people that were cropped and rescaled so that only the area around the eyes is visible. The participant is asked to select, within 20 seconds, the word which best describes what the person in the photo is thinking or feeling. Relevant to this report, the annual MYHAT assessment also included the following items: <i>Demographics:</i> age, sex, race (white/ non-white), level of education <i>Cognitive screen:</i> Mini-Mental State Examination [MMSE] <i>Literacy:</i> Wechsler Test of Adult Reading [WTAR] <i>Depression symptoms</i>: modified Center for Epidemiological Studies- Depression scale [mCES-D] <i>Anxiety symptoms:</i> Generalized Anxiety Disorder brief scale [GAD-7] <i>Cognitive Composites</i>: composite scores derived for the domains of attention, memory, language, visuospatial function, and executive function, derived from our neuropsychological test battery. <i>Social Norms:</i> Social Norms Questionnaire [SNQ-22] <i>Dementia Rating:</i> Clinical Dementia Rating [CDR®] Staging Instrument. On the CDR, ratings of 0, 0.5, and ≥1 indicate normal cognition, mild cognitive impairment or very mild dementia, and at least mild dementia. <h3>Results</h3> A total of 902 older adults age 66 to 105 years were administered RMET-10. The mean (SD) age of 76.6 (8.06) years; 62.4% were women; 38.9% had high school or less education; 61% had more than high school education; and 93.7% were of European descent. The RMET-10 scores were roughly normally distributed in our overall study sample with a range of 0-10, a median score of 7, and a mean (SD) score of 6.5 (1.9), and also among those with CDR=0, with range 0-10, median 7 and mean (SD) 6.64 (1.8). Mean (SD) RMET-10 scores were calculated for each of the categories in age, sex, education, race, MMSE, WTAR, SNQ-22, GAD-7, mCES-D, and CDR. The RMET-10 score was estimated to be significantly higher among those with younger age, higher education, white race, lower CDR, higher MMSE, WTAR, and higher cognitive scores in all five domains. Women performed significantly better than men only in the age group 65-74 years. In multivariable regression models adjusted for age, sex, and education, all the above associations remained statistically significant. RMET-10 score was also significantly higher in those with fewer anxiety and depression symptoms after adjusting for demographics. <h3>Conclusions</h3> Social cognition is relevant to the behavior and interactions of older adults and can be measured with a simple scale. Our population-based norms on the RMET could prove useful to clinicians and other researchers in calibrating the scale for their own patients and study participants. Using the scale as a continuous measure, clinicians can assess their patients' social cognition bearing in mind that test scores will be influenced by age, sex, race, and education, as well as by anxiety and depression. <h3>Funding</h3> The work reported here was supported in part by grant # R01AG023651 from the National Institute on Aging, NIH, US DHHS.

Correspondence between blood‐based amyloid‐β by immuno‐precipitation mass spectrometry and PIB‐PET imaging in a population cohort

AbstractBackgroundRecently developed immuno‐precipitation mass spectrometry (IP‐MS) assays to measure blood‐based amyloid‐β with high accuracy holds exciting potential. Adoption of amyloid‐β measurement will be especially valuable in large population studies where not previously feasible. We evaluated the correspondence between a new IP‐MS assay developed on a commercially available platform with brain amyloid PET imaging as the gold standard.MethodN=99 older participants without dementia, active in the population‐based Monongahela‐Youghiogheny Healthy Aging Team (MYHAT) study, underwent blood draws at the time of brain amyloid imaging with PiB‐PET (50‐70 minutes post‐injection, SUVR with cerebellar reference). Adapting methods of Nakamura et al. (2018), immunoprecipitation from plasma was followed by time‐of‐flight MS, using a benchtop mass spectrometer, to measure relative amounts of endogenous peptides Aβ1‐40, Aβ1‐42, APP669‐711, and a stable‐isotope‐labeled internal standard. A composite plasma biomarker was calculated as the mean of the normalized ratios APP669711/Aβ142 and Aβ140/Aβ142.Resultn= 24 (24%) of participants were PiB‐positive by a global cutoff, 7 (7%) were CDR 0.5, and 13 (13%) were APOE*4 carriers. Higher global PiB SUVR was associated with older age, higher CDR (0.5 vs. 0) and APOE*4 genotype (p’s &lt; .05), while higher plasma composite biomarker was similarly associated with CDR and APOE*4 but not age. ROC analysis yielded an AUC of 0.78 (SE 0.05) for the composite plasma biomarker predicting PiB‐PET status, with an optimized cut‐point corresponding to sensitivity of 0.75 and specificity of 0.69. Including age and APOE*4 into the model yielded an overall AUC of 0.89, and plasma biomarker sensitivity of 0.91 and specificity of 0.77.ConclusionThis IP‐MS assay was successfully implemented using a commercially‐available, benchtop MALDI‐TOF instrument that is easy to operate and already used in clinic settings. Concurrent prediction of amyloid status from plasma amyloid alone was significant, with moderately high accuracy. Combining plasma amyloid with age and APOE genotype improved prediction to high accuracy. Planned follow‐up of the sample with repeat PiB scans will yield yet further information about prospective prediction of brain amyloid status. This non‐invasive approach using a peripheral biomarker could be highly useful and feasible to apply in large population studies of AD risk.

Alzheimer's disease pathology in a community-based sample of older adults without dementia: The MYHAT neuroimaging study.

A true understanding of the distribution and functional correlates of Alzheimer's disease pathology in dementia-free older adults requires a population-based perspective. Here we report initial findings from a sample of 102 cognitively unimpaired participants (average age 77.2 years, 54.9% women, 13.7% APOE*4 carriers) recruited for neuroimaging from a larger representative population-based cohort participating in an ongoing longitudinal study of aging, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT). All participants scored < 1.0 on the Clinical Dementia Rating (CDR) Scale, with 8 participants (7.8%) scoring CDR = 0.5. Participants completed a positron emission tomography scan using the tracers [C-11]Pittsburgh Compound-B (PiB) and [F-18]AV-1451 to estimate amyloid and tau deposition. PiB positivity was defined on a regional basis using established standardized uptake value ratio cutoffs (SUVR; cerebellar gray matter reference), with 39 participants (38.2%) determined to be PiB(+). Health history, lifestyle, and cognitive abilities were assessed cross-sectionally at the nearest annual parent MYHAT study visit. A series of adjusted regression analyses modeled cognitive performance as a function of global PiB SUVR and [F-18]AV-1451 SUVR in Braak associated regions 1, 3/4, and 5/6. In comparison to PiB(-) participants (n = 63), PiB(+) participants were older, less educated, and were more likely to be APOE*4 carriers. Global PiB SUVR was significantly correlated with [F-18]AV-1451 SUVR in all Braak-associated regions (r = .38-0.53, p < .05). In independent models, higher Global PiB SUVR and Braak 1 [F-18]AV-1451 SUVR were associated with worse performance on a semantic interference verbal memory test. Our findings suggest that brain amyloid is common in a community-based setting, and is associated with tau deposition, but both pathologies show few associations with concurrent cognitive performance in a dementia-free sample.

Executive function predicts decline in mobility after a fall: The MYHAT study.

Evidence suggests that better cognitive functioning is associated with better mobility in older age. It is unknown whether older adults with better cognitive function are more resilient to mobility decline after a fall. Participants from the Monongahela Youghiogheny Healthy Aging Team (MYHAT) study were followed annually for up to 9years for incident falls. We examined one-year (mean 1.0year, SD 0.1) change in mobility pre- to post-fall using the Timed Up and Go (TUG) in relation to pre-fall cognition (executive function, attention, memory, and visuospatial function) among incident fallers (n=598, mean age 79.1, SD=7.0). Linear regression models tested the association of cognition with change in TUG. Interaction terms were tested to explore if age, sex, body mass index, physical activity, depressive symptoms, or visual acuity modified the associations of cognition and mobility among fallers. The association between cognition and one-year change in TUG was also tested in a comparison sample of non-fallers (n=442, mean age 76.3, SD=7.2). Overall, mobility decline was greater in fallers compared to non-fallers. In fully-adjusted models, higher executive function, but not attention, memory, or visuospatial function, was associated with less decline in mobility among incident fallers. The effect was significantly stronger for those who were older, sedentary, and had lower body mass index. Higher scores in memory tests, but not in other domains, was associated with less mobility decline among non-fallers. Higher executive function may offer resilience to mobility decline after a fall, especially among older adults with other risk factors for mobility decline. Future studies should assess whether executive function may be a helpful risk index of fall-related physical functional decline in geriatric settings.

Declining Incident Dementia Rates Across Four Population-Based Birth Cohorts.

Incidence rates of dementia appear to be declining in high-income countries according to several large epidemiological studies. We aimed to describe declining incident dementia rates across successive birth cohorts in a U.S. population-based sample and to explore the influences of sex and education on these trends. We pooled data from two community-sampled prospective cohort studies with similar study aims and contiguous sampling regions: the Monongahela Valley Independent Elders Survey (1987-2001) and the Monongahela-Youghiogheny Healthy Aging Team (2006-Ongoing). We identified four decade-long birth cohorts spanning birth years 1902-1941. In an analysis sample of 3,010 participants (61% women, mean baseline age = 75.7 years, mean follow-up = 7.1 years), we identified 257 cases of incident dementia indicated by a Clinical Dementia Rating of 1.0 or higher. We used Poisson regression to model incident dementia rates by birth cohort, age, sex, education, and interactions of Sex × Cohort and Sex × Education. We further examined whether cohort effects varied by education, testing a Cohort × Education interaction and stratifying the models by education. Compared to the earliest birth cohort (1902-1911), each subsequent cohort had a significantly lower incident dementia rate (1912-1921: incidence rate ratio [IRR] = 0.655, 95% confidence interval [95% CI] = 0.477-0.899; 1922-1931: IRR = 0.387, 95% CI = 0.265-0.564; 1932-1941: IRR = 0.233, 95% CI = 0.121-0.449). We observed no significant interactions of either sex or education with birth cohort. A decline in incident dementia rates was observed across successive birth cohorts independent of sex, education, and age.

Longitudinal changes in physical function and physical activity in older adults.

physical function (PF) and physical activity (PA) both decline as adults age and have been linked to negative outcomes, including dementia, depression and cardiovascular diseases. Although declines in each are associated with numerous negative outcomes, the longitudinal relationship between these two measures is unclear. to examine the dynamic, bidirectional associations between declines in PF and PA. prospective cohort. the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. about 1,404 men and women, 76.96 ± 7.2 years, 62.4% female and 95.2% white. over nine annual assessment cycles, PF was evaluated via the timed Up-and-Go task and PA via a self-reported questionnaire. Piecewise latent growth models examined bidirectional associations between PA and PF to determine whether the initial values (intercept) or early slope (cycles 1-5) (in either PF or PA) predicted later slope (cycles 5-9) (in either PF or PA). initial PF significantly predicted early (standardised β= -0.10, P < 0.001) and later (standardised β= -0.09, P = 0.01) PA slopes. Initial PA significantly predicted later (standardised β = -0.09, P = 0.04) but not early PF slope. Associations were independent of baseline memory test scores, baseline cognitive status, later cognitive status and age. Early physical function slope neither predicts later PA slope nor did early PA slope predict later PF slope (both P values >0.10). the relationship between PF and PA is bidirectional, with PF more consistently predicting declines of PA, both in the short- and long-term. Intervening on PF impairments may improve PA engagement, which could in turn promote PF and translate to beneficial effects on cognitive function, cardiovascular health and mood.

Engagement in social activities and progression from mild to severe cognitive impairment: the MYHAT study

It is of considerable public health importance to prevent or delay the progression of mild cognitive impairment (MCI) to more severely impaired cognitive states. This study examines the risk of progression from mild to severe cognitive impairment in relation to engagement in social activities while mildly impaired and the concurrence of subsequent change in engagement with MCI progression. Participants were 816 older adults with cognitively defined MCI (mean age 78.0 (standard deviation or SD = 7.4) years) from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) Study--a prospective cohort study of MCI in the community. Over three years of follow-up, 78 individuals progressed from MCI to severe cognitive impairment, while 738 did not progress. Risk of progression was estimated using discrete time survival analyses. The main predictors were standardized composite measures of the variety and frequency of engagement in social activities. Lower risk of progression from mild to severe cognitive impairment was associated with both a greater level of frequency of engagement in social activities while mildly impaired (OR = 0.72, 95% CI: 0.55-0.93, p = 0.01) and also with a slower rate of decline in the variety of activities over time (OR = 0.01, 95% CI: <0.001-0.38, p = 0.02). Greater engagement in social activities may potentially be beneficial for preventing or delaying further cognitive decline among older adults with MCI. Alternatively, lesser engagement in social activities may be a marker of impending cognitive decline in MCI.

Prevalence of Mild Cognitive Impairment by Multiple Classifications: The Monongahela-Youghiogheny Healthy Aging Team (MYHAT) Project

To estimate and compare the frequency and prevalence of mild cognitive impairment (MCI) and related entities using different classification approaches at the population level. Cross-sectional epidemiologic study of population-based cohort recruited by age-stratified random sampling from electoral rolls. Small-town communities in western Pennsylvania. Of 2,036 individuals aged 65 years and older, 1,982 participants with normal or mildly impaired cognition (age-education-corrected Mini-Mental State scores ≥ 21). Demographics, neuropsychological assessment expressed as cognitive domains, functional ability, and subjective reports of cognitive difficulties; based on these measurements, operational criteria for the Clinical Dementia Rating (CDR) scale, the 1999 criteria for amnestic MCI, the 2004 Expanded criteria for MCI, and new, purely cognitive criteria for MCI. A CDR rating of 0.5 (uncertain/very mild dementia) was obtained by 27.6% of participants, whereas 1.2% had CDR ≥ 1 (mild or moderate dementia). Among those with CDR <1, 2.27% had amnestic MCI and 17.66% had expanded MCI, whereas 35.17% had MCI by purely cognitive classification. Isolated executive function impairment was the least common, whereas impairment in multiple domains including executive function was the most common. Prevalence estimates weighted against the U.S. Census are also provided. The manner in which criteria for MCI are operationalized determines the proportion of individuals who are thus classified and the degree of overlap with other criteria. Prospective follow-up is needed to determine progression from MCI to dementia and thus empirically develop improved MCI criteria with good predictive value.

A novel approach to assessing memory at the population level: vulnerability to semantic interference

There is increasing interest in identifying novel cognitive paradigms to help detect preclinical dementia. Promising results have been found in clinical settings using the Semantic Interference Test (SIT), a modification of an existing episodic memory test (Fuld Object Memory Evaluation) that exploits vulnerability to semantic interference in Alzheimer's disease. It is not yet known how broadly this work will generalize to the community at large. Participants aged > or = 65 years from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) were administered the SIT at study entry. Independent of neuropsychological assessment, participants were rated on the Clinical Dementia Rating (CDR) scale, based on reported loss of cognitively driven everyday functioning. In individuals free of dementia (CDR < 1), the concurrent validity of the SIT was assessed by determining its association with CDR using multiple logistic regression models, with CDR 0 (no dementia) vs. 0.5 (possible dementia) as the outcome and the SIT test variables as predictors. Poorer performance on all SIT variables but one was associated with higher CDR reflecting possible dementia (Odds Ratios 2.24-4.79). Younger age and female gender also conferred a performance advantage. Years of education and reading ability (a proxy for quality of education) evidenced a very weak association with SIT performance. The SIT shows promise as a valid, novel measure to identify early preclinical dementia in a community setting. It has potential utility for assessment of persons who may be illiterate or of low education. Finally, we provide normative SIT data stratified by age which may be utilized by clinicians or researchers in future investigations.

Age and education effects and norms on a cognitive test battery from a population-based cohort: The Monongahela–Youghiogheny Healthy Aging Team

Objectives: Performance on cognitive tests can be affected by age, education, and also selection bias. We examined the distribution of scores on several cognitive screening tests by age and educational levels in a population-based cohort. Method: An age-stratified random sample of individuals aged 65+ years was drawn from the electoral rolls of an urban US community. Those obtaining age and education-corrected scores ≥21/30 on the Mini-Mental State Examination (MMSE) were designated as cognitively normal or only mildly impaired, and underwent a full assessment including a battery of neuropsychological tests. Participants were also rated on the Clinical Dementia Rating (CDR) scale. The distribution of neuropsychological test scores within demographic strata, among those receiving a CDR of 0 (no dementia), are reported here as cognitive test norms. After combining individual test scores into cognitive domain composite scores, multiple linear regression models were used to examine associations of cognitive test performance with age and education. Results: In this cognitively normal sample of older adults, younger age and higher education were associated with better performance in all cognitive domains. Age and education together explained 22% of the variation of memory, and less of executive function, language, attention, and visuospatial function. Conclusion: Older age and lesser education are differentially associated with worse neuropsychological test performance in cognitively normal older adult representatives of the community at large. The distribution of scores in these participants can serve as population-based norms for these tests, and can be especially useful to clinicians and researchers assessing older adults outside specialty clinic settings.

How much do depressive symptoms affect cognition at the population level? The monongahela–youghiogheny healthy aging team (MYHAT) study

To examine the impact of subjective depressive symptoms on objective performance on tests of several cognitive domains, in a community-based sample of older adults. An age-stratified sample of 2036 individuals aged 65+ years was drawn from the electoral rolls of a U.S. community, excluding individuals with moderate to severe cognitive impairment. A cognitive test battery and a modified Center for Epidemiologic Studies-Depression scale (mCES-D) were completed by 1982 participants. Cognitive test scores were compared across levels of depressive symptoms, and composite scores created to represent cognitive domains of attention, language, memory, visuospatial, and executive function. Multivariable regression models tested the association of depressive symptoms with cognitive domain composite scores, adjusting for age, sex, race, and education. Most participants reported no depressive symptoms. Small differences in cognitive scores were observed on all tests among those with 0, 1-2, and > or = 3 symptoms. Adjusting for demographic variables, depressive symptoms remained associated with lower performance on all cognitive composites except attention, most strongly with executive function. Depressive symptoms explained <2% of the variance in test scores, less than that explained by age or education. In this population-based sample of older adults, restricted to those with normal or only mildly impaired cognition, a relatively small proportion reported any depressive symptoms. The number of depressive symptoms had strong statistically significant associations with performance in most cognitive domains. However, depressive symptoms explained little of the variance in cognitive performance, with relatively small differences in scores among those with and without symptoms.

Effects of age, gender, education and race on two tests of language ability in community-based older adults

Neuropsychological tests, including tests of language ability, are frequently used to differentiate normal from pathological cognitive aging. However, language can be particularly difficult to assess in a standardized manner in cross-cultural studies and in patients from different educational and cultural backgrounds. This study examined the effects of age, gender, education and race on performance of two language tests: the animal fluency task (AFT) and the Indiana University Token Test (IUTT). We report population-based normative data on these tests from two combined ethnically divergent, cognitively normal, representative population samples of older adults. Participants aged > or =65 years from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) and from the Indianapolis Study of Health and Aging (ISHA) were selected based on (1) a Clinical Dementia Rating (CDR) score of 0; (2) non-missing baseline language test data; and (3) race self-reported as African-American or white. The combined sample (n = 1885) was 28.1% African-American. Multivariate ordinal logistic regression was used to model the effects of demographic characteristics on test scores. On both language tests, better performance was significantly associated with higher education, younger age, and white race. On the IUTT, better performance was also associated with female gender. We found no significant interactions between age and sex, and between race and education. Age and education are more potent variables than are race and gender influencing performance on these language tests. Demographically stratified normative tables for these measures can be used to guide test interpretation and aid clinical diagnosis of impaired cognition.