Feasibility and Psychometric Integrity of Mobile Phone-Based Intensive Measurement of Cognition in Older Adults.

Background:There is a pressing need for assessment approaches that can be deployed remotely to measure cognitive outcomes in clinical trials and longitudinal aging cohorts. We evaluated the utility of a mobile phone-based intensive measurement study for this purpose. Method:A small cohort of healthy older adults (N = 17, mean age = 73) completed five assessment "bursts" over 12 months, with each measurement burst involving two assessments daily for five consecutive days. Each assessment included brief tests of visual short-term memory and information processing speed, as well as surveys measuring state factors that can affect cognition. Results:At study endpoint we had 94% retention, 97% compliance, and high participant satisfaction. Mobile cognitive test scores demonstrated good reliability, moderate correlations with in-person baseline neuropsychological testing, and significant associations with participant age and education level. Conclusions: Mobile phone-based intensive measurement designs represent a promising assessment approach for measuring cognition longitudinally in older adults.

Progress and future challenges in aging and diversity research in the United States.

In 2016, the UC Davis Latino Aging Research Resource Center and UC Davis Alzheimer's Disease Center brought together experts from across the country to consolidate current knowledge and identify future directions in aging and diversity research. This report disseminates the research priorities that emerged from this conference, building on an earlier Gerontological Society of America preconference. We review key racial/ethnic differences in cognitive aging and dementia and identify current knowledge gaps in the field. We advocate for a systems-level framework for future research whereby environmental, sociocultural, behavioral, neuropathological, genetic, and psychometric levels of analysis are examined together to identify pathways and mechanisms that influence disparities. We then discuss steps to increase the recruitment and retention of racial/ethnic minorities in aging studies, as none of the recommendations will be possible without strong collaboration between racial/ethnic minority communities and researchers. This approach is consistent with the National Institute on Aging Health Disparities Research Framework.

Comparing Variability, Severity, and Persistence of Depressive Symptoms as Predictors of Future Stroke Risk.

OBJECTIVE: Numerous studies show that depressive symptoms measured at a single assessment predict greater future stroke risk. Longer-term symptom patterns, such as variability across repeated measures or worst symptom level, might better reflect adverse aspects of depression than a single measurement. This prospective study compared five approaches to operationalizing depressive symptoms at annual assessments as predictors of stroke incidence. DESIGN: Cohort followed for incident stroke over an average of 6.4 years. SETTING: The Adult Changes in Thought cohort follows initially cognitively intact, community- dwelling older adults from a population base defined by membership in Group Health, a Seattle-based nonprofit healthcare organization. PARTICIPANTS: 3,524 individuals aged 65 years and older. MEASUREMENTS: We identified 665 incident strokes using ICD codes. We considered both baseline Center for Epidemiologic Studies-Depression scale (CES-D) score and, using a moving window of three most recent annual CES-D measurements, we compared most recent, maximum, average, and intra-individual variability of CES-D scores as predictors of subsequent stroke using Cox proportional hazards models. RESULTS: Greater maximum (hazard ratio [HR]: 1.18; 95% CI: 1.07-1.30), average (HR: 1.20; 95% CI: 1.05-1.36) and intra-individual variability (HR: 1.15; 95% CI: 1.06-1.24) in CES-D were each associated with elevated stroke risk, independent of sociodemographics, cardiovascular risks, cognition, and daily functioning. Neither baseline nor most recent CES-D was associated with stroke. In a combined model, intra-individual variability in CES-D predicted stroke, but average CES-D did not. CONCLUSIONS: Capturing the dynamic nature of depression is relevant in assessing stroke risk. Fluctuating depressive symptoms may reflect a prodrome of reduced cerebrovascular integrity.

The dynamic relationship between physical function and cognition in longitudinal aging cohorts.

On average, older people remember less and walk more slowly than do younger persons. Some researchers argue that this is due in part to a common biologic process underlying age-related declines in both physical and cognitive functioning. Only recently have longitudinal data become available for analyzing this claim. We conducted a systematic review of English-language research published between 2000 and 2011 to evaluate the relations between rates of change in physical and cognitive functioning in older cohorts. Physical functioning was assessed using objective measures: walking speed, grip strength, chair rise time, flamingo stand time, and summary measures of physical functioning. Cognition was measured using mental state examinations, fluid cognition, and diagnosis of impairment. Results depended on measurement type: Change in grip strength was more strongly correlated with mental state, while change in walking speed was more strongly correlated with change in fluid cognition. Examining physical and cognitive functioning can help clinicians and researchers to better identify individuals and groups that are aging differently and at different rates. In future research, investigators should consider the importance of identifying different patterns and rates of decline, examine relations between more diverse types of measures, and analyze the order in which age-related declines occur.

Differential prediction of vascular dementia and Alzheimer's disease in nondemented older adults within 5 years of initial testing.

OBJECTIVE: To determine whether neuropsychological tests and the Hachinski Ischemic Score (HIS) can differentiate incident vascular dementia (VaD) from Alzheimer's disease (AD) in nondemented older adults within 5 years of initial testing. METHODS: The Canadian Study of Health and Aging (CSHA) included three waves: CSHA-1 (1991-1992), CSHA-2 (1996-1997), and CSHA-3 (2001-2002). This analysis included participants of the CSHA who (a) underwent neuropsychological testing and clinical assessment at CSHA-2 and were determined to be nondemented, and (b) underwent diagnostic assessment at CSHA-3. The outcome measure was CSHA-3 diagnosis, classified as VaD (n = 22), probable or possible AD (n = 65), and all other diagnostic outcomes (n = 417). CSHA-3 diagnosticians were blinded to CSHA-2 test scores and diagnoses. Multinomial logistic regression with forward selection was used to determine the ability of the HIS and 15 CSHA-2 neuropsychological tests to predict CSHA-3 diagnostic outcome. The analysis was repeated after removing 15 AD cases with coexisting vascular disease. RESULTS: The HIS and four neuropsychological tests were significant predictors of CSHA-3 diagnostic outcome (χ2 (14) = 149.59, P < .001, R2 = 0.38). Relative to developing VaD, higher HIS (odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.57-0.86) and Rey Auditory Verbal Learning Test immediate verbal recall scores (OR: 0.77; 95% CI: 0.62-0.97) were associated with lowered odds of developing AD, whereas higher phonemic fluency scores (OR: 1.21; 95% CI: 1.02-1.17) were associated with increased odds of developing AD. Removing AD cases with vascular disease did not affect results. CONCLUSIONS: In an epidemiological sample of nondemented participants, the HIS and two neuropsychological tests contributed to the differential prediction of VaD and AD within 5 years of initial measurement.

Sex differences in face processing are mediated by handedness and sexual orientation.

Previous research has demonstrated sex differences in face processing at both neural and behavioural levels. The present study examined the role of handedness and sexual orientation as mediators of this effect. We compared the performance of LH (left-handed) and RH (right-handed) heterosexual and homosexual male and female participants on a face recognition memory task. Our main findings were that homosexual males have better face recognition memory than both heterosexual males and homosexual women. We also demonstrate better face processing in women than in men. Finally, LH heterosexual participants had better face recognition than LH homosexual participants and also tended to be better than RH heterosexual participants. These findings are consistent with differences in the organisation and laterality of face-processing mechanisms as a function of sex, handedness, and sexual orientation.

Telephone administration of the Mental Alternation Test: sensitivity to cognitive decline and practice effects across midlife and late life.

BACKGROUND: We evaluated the utility of the telephone-administered Mental Alternation Test (MAT, an oral variant of the Trail-Making Test) for remote assessment of cognitive functioning in older adults. We examined (1) the sensitivity of MAT scores to cognitive change across 4 age groups, (2) practice effects associated with repeat administration, and (3) the uniformity of practice effects across age groups. METHODS: Community-dwelling volunteers were recruited randomly and categorized as young-middle-aged (45-54 years; n = 51), middle-aged (55-64 years; n = 58), young-old (65-74 years; n = 43) or old-old (75-85 years; n = 43). The participants completed the MAT twice within 2 weeks. The data were analyzed using mixed ANOVA. RESULTS: We found an effect of age on MAT performance [F(3, 191) = 11.37; p < 0.001], with planned comparisons revealing significantly lower scores in the old-old (p < 0.05). The scores on the second MAT administration were significantly higher than on the first administration [F(1, 191) = 12.82; p < 0.001], but this practice effect did not differ across age groups. CONCLUSIONS: The MAT was sensitive to cognitive decline in older adulthood. Practice effects were measurable but uniform across the observed age cohorts. As a brief telephone-administered test, the MAT represents a promising measure of cognitive functioning in older adults that is feasible for use in large-scale epidemiological studies.

A Comprehensive Comparison of Quantifications of Intraindividual Variability in Response Times: A Measurement Burst Approach.

OBJECTIVES: To formally identify and contrast the most commonly-employed quantifications of response time inconsistency (RTI) and elucidate their utility for understanding within-person (WP) and between-person (BP) variation in cognitive function with increasing age. METHOD: Using two measurement burst studies of cognitive aging, we systematically identified and computed five RTI quantifications from select disciplines to examine: (a) correlations among RTI quantifications; (b) the distribution of BP and WP variation in RTI; and (c) the comparability of RTI quantifications for predicting attention switching. RESULTS: Comparable patterns were observed across studies. There was significant variation in RTI BP as well as WP across sessions and bursts. Correlations among RTI quantifications were generally strong and positive both WP and BP, except for the coefficient of variation. Independent prediction models indicated that slower mean response time (RT) and greater RTI were associated with slower attention switching both WP and BP. For selecting simultaneous prediction models, collinearity resulted in inflated standard errors and unstable model estimates. DISCUSSION: RTI reflects a novel dimension of performance that is a robust and theoretically informative predictor of BP and WP variation in cognitive function. Among the plenitude of RTI quantifications, not all are interchangeable, nor of comparable predictive utility.

Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding.

PURPOSE: Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke. METHODS: For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study-Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other. RESULTS: Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0-2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not. CONCLUSIONS: Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions.

Contrasting olfaction, vision, and audition as predictors of cognitive change and impairment in non-demented older adults.

OBJECTIVE: This study examines the relative utility of a particular class of noninvasive functional biomarkers-sensory functions-for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether (a) olfactory function, vision, and audition exhibited significant longitudinal declines in nondemented older adults; (b) multiwave change for these sensory function indicators predicted risk of mild cognitive impairment (MCI); and (c) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. METHOD: A longitudinal sample (n = 408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively, single-assessment MCI, and multiple-assessment MCI. RESULTS: We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. CONCLUSIONS: These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multistep screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. (PsycINFO Database Record

Concurrent Indicators of Gait Velocity and Variability Are Associated with 25-Year Cognitive Change: A Retrospective Longitudinal Investigation.

Background/Objectives: Physical function indicators, including gait velocity, stride time and step length, are linked to neural and cognitive function, morbidity and mortality. Whereas cross-sectional associations are well documented, far less is known about long-term patterns of cognitive change as related to objective indicators of mobility-related physical function. Methods: Using data from the Victoria Longitudinal Study, a long-term investigation of biological and health aspects of aging and cognition, we examined three aspects of cognition-physical function linkages in 121 older adults. First, we examined a simple marker of physical function (3 m timed-walk) as a predictor of cross-sectional differences and up to 25-year change for four indicators of cognitive function. Second, we tested associations between two markers of gait function derived from the GAITRite system (velocity and stride-time variability) and differences and change in cognition. Finally, we evaluated how increasing cognitive load during GAITRite assessment influenced the associations between gait and cognition. Results: The simple timed-walk measure, commonly used in clinical and research settings, was a minor predictor of change in cognitive function. In contrast, the objectively measured indicator of walking speed significantly moderated long-term cognitive change. Under increasing cognitive load, the moderating influence of velocity on cognitive change increased, with increasing variability in stride time also emerging as a predictor of age-related cognitive decline. Conclusion: These findings: (a) underscore the utility of gait as a proxy for biological vitality and for indexing long-term cognitive change; and (b) inform potential mechanisms underlying age-related linkages in physical and cognitive function.

Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality.

INTRODUCTION: We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. METHODS: We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years. RESULTS: Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00-1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41-1.00, P = .05). DISCUSSION: Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.

Early life development in a multiethnic sample and the relation to late life cognition.

OBJECTIVES: Poor quality of early life conditions has been associated with poorer late life cognition and increased risk of dementia. Early life physical development can be captured using adult measures of height and head circumference. Availability of resources may be reflected by socioeconomic indicators, such as parental education and family size. We sought to determine the association between early life development and experience and late life semantic memory, episodic memory, and executive functioning abilities, as well as rate of cognitive decline. METHOD: This study was conducted using the UC Davis Aging Diversity cohort, an ethnically diverse sample of Caucasian, African American, and Hispanic individuals from northern California. We used latent variable modeling to measure growth and childhood socioeconomic environment (SES) and examine their associations with longitudinal cognitive outcomes using mixed effects modeling. RESULTS: Growth was positively related to higher childhood SES. Higher childhood SES was associated with better semantic memory. Both low growth and low SES were associated with increased rate of cognitive decline. DISCUSSION: These findings demonstrate that early life experiences influence the trajectory of cognitive aging. Early life development and experience appears to provide a distal basis upon which additional risk and protective factors interact in the development of dementia.

Measurement equivalence of neuropsychological tests across education levels in older adults.

OBJECTIVE: The objective was to determine whether neuropsychological tests provide an equivalent measure of the same psychological constructs in older adults with low versus higher levels of education. METHOD: Confirmatory factor analysis was used to evaluate the fit of a three-factor model (Verbal Ability, Visuospatial Ability, Long-Term Retention) to scores from the neuropsychological battery of the Canadian Study of Health and Aging (CSHA). Measurement equivalence of the model across lower educated (LE; ≤8 years) and higher educated (HE; ≥9 years) participants was evaluated using invariance testing. RESULTS: The measurement model demonstrated adequate fit across LE and HE samples but the loadings of the 11 tests onto the three factors could not be constrained equally across groups. Animal Fluency and the Token Test were identified as noninvariant tests of Verbal Ability that, when freed from constraints, produced a partial metric invariance model. Scalar invariance testing identified the Buschke Cued Recall Test and Block Design as measures with invariant factor loadings but noninvariant intercepts. Analyses were replicated in age- and sex-matched subsamples. CONCLUSIONS: Metric and scalar invariance across HE and LE samples was achieved for seven of the 11 tests in the CSHA battery. Animal Fluency and the Token Test were noninvariant measures of Verbal Ability, suggesting that cognitive processes underlying performance on these tests may vary as a function of education. In addition, scores from Block Design and the Buschke Cued Recall Test were observed to differ in their scale of measurement between HE and LE examinees.

Life experience and demographic influences on cognitive function in older adults.

OBJECTIVE: We examined the influence of a broad spectrum of life experiences on longitudinal cognitive trajectories in a demographically diverse sample of older adults. METHOD: Participants were 333 educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. Mixed-effects regression was used to measure baseline status in episodic memory, executive functioning, and semantic memory and change in a global cognition factor defined by change in these 3 domain-specific measures. We examined effects of life experience variables (literacy, childhood socioeconomic status, morphometric measures of physical development, life course physical and recreational activity) on longitudinal cognitive trajectories, covarying for age, apolipoprotein E (APOE) genotype and demographics (education, ethnicity, language). RESULTS: Non-Latino Whites had higher baseline cognition, but life experience variables attenuated ethnic differences in cognitive scores. Age, literacy, childhood socioeconomic status, and physical activity significantly influenced baseline cognition. Age, APOE ε4, and decline in intellectually and socially stimulating recreational activity from mid to late life were independently associated with increased late life cognitive decline. Higher literacy and late life recreational activity were associated with less decline. Literacy had similar effects for English and Spanish readers/speakers. Bilingual English and Spanish speakers did not differ from English Speakers in cognitive performance. CONCLUSIONS: Life experience variables, especially literacy level, were strongly related to baseline cognition and substantially attenuated effects of race/ethnicity and education. Cognitive change was best explained by age, APOE ε4, literacy, and current recreational activities. Literacy had robust associations with baseline cognition and cognitive change in both English and Spanish speakers.

Mental alternation test: administration mode, age, and practice effects.

Administration mode, age, education, and practice effects were examined for the Mental Alternation Test (MAT), a brief orally administered measure of executive function. Participants (N = 135) between the ages of 65 and 85 years completed the MAT twice in person, twice over the telephone, or once in person and once over the telephone. MAT scores did not differ across administration modes. Furthermore, the MAT detected normative decreases in executive ability in later life. The correlation between MAT performance and educational attainment was small. Finally, practice effects, which were influenced by age, were found between administration times. These findings provide important implications for both research and clinical applications of the MAT in older populations.