Chung Chou H Chang

Outcomes of mild cognitive impairment by definition: a population study.

BACKGROUNDnMild cognitive impairment (MCI) has been defined in several ways.nnnOBJECTIVEnTo determine the 1-year outcomes of MCI by different definitions at the population level.nnnDESIGNnInception cohort with 1-year follow-up. Participants were classified as having MCI using the following definitions operationalized for this study: amnestic MCI by Mayo criteria, expanded MCI by International Working Group criteria, Clinical Dementia Rating (CDR) = 0.5, and a purely cognitive classification into amnestic and nonamnestic MCI.nnnSETTINGnGeneral community.nnnPARTICIPANTSnStratified random population-based sample of 1982 individuals 65 years and older.nnnMAIN OUTCOME MEASURESnFor each MCI definition, there were 3 possible outcomes: worsening (progression to dementia [CDR ≥ 1] or severe cognitive impairment), improvement (reversion to CDR = 0 or normal cognition), and stability (unchanged CDR or cognitive status).nnnRESULTSnRegardless of MCI definition, over 1 year, a small proportion of participants progressed to CDR > 1 (range, 0%-3%) or severe cognitive impairment (0%-20%) at rates higher than their cognitively normal peers. Somewhat larger proportions of participants improved or reverted to normal (6%-53%). Most participants remained stable (29%-92%). Where definitions focused on memory impairment and on multiple cognitive domains, higher proportions progressed and lower proportions reverted on the CDR.nnnCONCLUSIONSnAs ascertained by several operational definitions, MCI is a heterogeneous entity at the population level but progresses to dementia at rates higher than in normal elderly individuals. Proportions of participants progressing to dementia are lower and proportions reverting to normal are higher than in clinical populations. Memory impairments and impairments in multiple domains lead to greater progression and lesser improvement. Research criteria may benefit from validation at the community level before incorporation into clinical practice.

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

BACKGROUNDnNeuropsychological 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.nnnMETHODSnParticipants 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.nnnRESULTSnOn 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.nnnCONCLUSIONSnAge 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.

Terminal decline and practice effects in older adults without dementia The MoVIES project

Objective: To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline. Methods: A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point. Results: Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects. Conclusions: Terminal cognitive decline in older adults without dementia may reflect presymptomatic disease which does not cross the clinical threshold during life. Alternatively, cognitive decline attributed to normal aging may itself represent underlying neurodegenerative or vascular pathology. Although we cannot conclude definitively from this study, the separation of practice effects from age-associated decline could help identify preclinical dementia. Neurology® 2011;77:722–730

Risk of Alzheimer's disease incidence attributable to vascular disease in the population

Although Alzheimers disease (AD) is a neurodegenerative disorder, there is growing interest in the influence of vascular factors on its incidence.

Vascular risk factors and cognitive decline in a population sample

We examined several vascular factors in relation to the rates of decline in 5 cognitive domains in a population-based cohort. In an age-stratified random sample (N=1982) aged 65+ years, we assessed at baseline the cognitive domains of attention, executive function, memory, language, and visuospatial function, and also vascular, inflammatory, and metabolic indices. Random effects models generated slopes of cognitive decline over the next 4 years; linear models identified vascular factors associated with these slopes, adjusting for demographics, baseline cognition, and potential interactions. Several vascular risk factors (history of stroke, diabetes, central obesity, C-reactive protein), although associated with lower baseline cognitive performance, did not predict rate of subsequent decline. APOE*4 genotype was associated with accelerated decline in language, memory, and executive functions. Homocysteine elevation was associated with faster decline in executive function. Hypertension (history or systolic blood pressure >140 mm Hg) was associated with slower decline in memory. Baseline alcohol consumption was associated with slower decline in attention, language, and memory. Different indices of vascular risk are associated with low performance and with rates of decline in different cognitive domains. Cardiovascular mechanisms explain at least some of the variance in cognitive decline. Selective survival may also play a role.

Dual Trajectories of Depression and Cognition: A Longitudinal Population-Based Study.

OBJECTIVEnTo examine the relationships over time between dual trajectories of depressive symptoms and several cognitive domains.nnnMETHODSnIn a 5-year longitudinal study, 1,978 randomly selected individuals aged 65+ years at recruitment were assessed annually. Repeated measures were of depressive symptoms on the modified Center for Epidemiologic Studies Depression Scale and composite scores in the cognitive domains of attention, executive function, memory, language, and visuospatial function. Latent class trajectories were identified for depression and for each cognitive domain and their associations investigated using dual trajectory modeling. Cognitive trajectories with z scores belowxa0-1 were designated as persistently low.nnnRESULTSnFive depressive symptom trajectories were observed: rarely depressed (60.5%); low-grade, decreasing symptoms (18.5%); low-grade, increasing symptoms (9.6%); moderate-grade symptoms (7.4%); and consistent higher-grade symptoms (4.0%). For each cognitive domain six trajectories were observed. The rarely depressed and low-grade decreasing symptom groups were the least likely to have persistently low cognition. The symptom trajectory most strongly associated with persistently low functioning in each domain was not the higher-grade group but rather the low-grade increasing group in the case of attention and the moderate-grade trajectory in the other four domains.nnnCONCLUSIONnConsistently higher-grade depressive symptoms are less strongly associated with poor cognitive functioning than with either moderate- or low-grade increasing depressive symptom trajectories, over time and across different domains. Examining both depression and cognition longitudinally allows heterogeneity of both to be addressed, revealing latent groups with potential diagnostic and prognostic implications.

COGNITIVE TEST PERFORMANCE PREDICTS CHANGE IN FUNCTIONAL STATUS AT THE POPULATION LEVEL. THE MYHAT PROJECT

In the community at large, many older adults with minimal cognitive and functional impairment remain stable or improve over time, unlike patients in clinical research settings, who typically progress to dementia. Within a prospective population-based study, we identified neuropsychological tests predicting improvement or worsening over 1 year in cognitively driven everyday functioning as measured by Clinical Dementia Rating (CDR). Participants were 1682 adults aged 65+ and dementia-free at baseline. CDR change was modeled as a function of baseline test scores, adjusting for demographics. Among those with baseline CDR = 0.5, 29.8% improved to CDR = 0; they had significantly better baseline scores on most tests. In a stepwise multiple logistic regression model, tests which remained independently associated with subsequent CDR improvement were Category Fluency, a modified Token Test, and the sum of learning trials on Object Memory Evaluation. In contrast, only 7.1% with baseline CDR = 0 worsened to CDR = 0.5. They had significantly lower baseline scores on most tests. In multiple regression analyses, only the Mini-Mental State Examination, delayed memory for visual reproduction, and recall susceptible to proactive interference, were independently associated with CDR worsening. At the population level, changes in both directions are observable in functional status, with different neuropsychological measures predicting the direction of change.

Exploring the nexus of Alzheimer's disease and related dementias with cancer and cancer therapies: A convening of the Alzheimer's Association & Alzheimer's Drug Discovery Foundation

Recent population studies suggest an intriguing inverse relationship between several types of cancer and neurodegenerative diseases, including Alzheimers disease. Understanding the intersection of the underlying biology for these two distinct families of diseases with one another may offer novel approaches to identify new therapeutic approaches and possible opportunities to repurpose existing drug candidates. The Alzheimers Association and the Alzheimers Drug Discovery Foundation convened a one‐day workshop to delve into this discussion. Workshop participants outlined research focus areas, potential collaborations, and partnerships for future action.

Cohort effects in verbal memory function and practice effects: A population-based study

BACKGROUNDnIn many developed countries, cognitive functioning (as measured by neuropsychological tests) appears to be improving over time in the population at large, in parallel with the declining age-specific incidence of dementia. Here, we investigated cohort effects in the age-associated trajectories of verbal memory function in older adults. We sought to determine whether they varied by decade of birth and, if so, whether the change would be explained by increasing educational attainment.nnnMETHODSnPooling data from two prospective US population-based studies between 1987 and 2015, we identified four birth cohorts born 1902-1911, 1912-1921, 1922-1931, and 1932-1943. Among these cohorts, we compared age-associated trajectories both of performance and of practice effects on immediate and delayed recall of a 10-item Word List. We used mixed effects models, first including birth cohorts and cohort X age interaction terms, and then controlling for education and education X age interaction.nnnRESULTSnWe observed significant cohort effects in performance (baseline and age-associated trajectories) in both immediate recall and delayed recall, with function improving between the earliest- and latest-born cohorts. For both tests, we also observed cohort effects on practice effects with the highest levels in the latest-born cohorts. Including education in the models did not attenuate these effects.nnnCONCLUSIONSnIn this longitudinal population study, across four decade-long birth cohorts, there were significant improvements in test performance and practice effects in verbal memory tests, not explained by education. Whether this reflects declining disease incidence or other secular trends awaits further investigation.

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

BACKGROUNDnThere 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 Alzheimers disease. It is not yet known how broadly this work will generalize to the community at large.nnnMETHODSnParticipants 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.nnnRESULTSnPoorer 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.nnnCONCLUSIONSnThe 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.