Trajectories Of Cognitive Aging Research Articles

Three-year changes in leisure activities are associated with concurrent changes in white matter microstructure and perceptual speed in individuals aged 80 years and older

Accumulating evidence suggests that engagement in leisure activities is associated with favorable trajectories of cognitive aging, but little is known about brain changes related to both activities and cognition. White matter microstructure shows experience-dependent plasticity and declines in aging. Therefore, we investigated the role of change in white matter microstructure in the activities-cognition link. We used repeated assessments of engagement, perceptual speed, and white matter microstructure (probed with diffusion tensor imaging) in a population-based sample of individuals over 80 years without dementia (n = 442, Mage = 85.1; n = 70 for diffusion tensor imaging; 2 occasions 3 years apart). Using multivariate latent change modeling, we observed positive correlations among changes in predominantly social activities, white matter microstructure, and perceptual speed. Interindividual differences in change in white matter microstructure statistically accounted for the association between change in leisure activities and change in perceptual speed. However, as analyses are based on observational data from 2 measurement occasions, causality remains unclear.

Change in Cognitive Abilities in Older Latinos.

The aim of this study was to compare patterns of cognitive decline in older Latinos and non-Latinos. At annual intervals for a mean of 5.7 years, older Latino (n=104) and non-Latino (n=104) persons of equivalent age, education, and race completed a battery of 17 cognitive tests from which previously established composite measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability were derived. In analyses adjusted for age, sex, and education, performance declined over time in each cognitive domain, but there were no ethnic group differences in initial level of function or annual rate of decline. There was evidence of retest learning following the baseline evaluation, but neither the magnitude nor duration of the effect was related to Latino ethnicity, and eliminating the first two evaluations, during which much of retest learning occurred, did not affect ethnic group comparisons. Compared to the non-Latino group, the Latino group had more diabetes (38.5% vs. 25.0; χ2[1]=4.4; p=.037), fewer histories of smoking (24.0% vs. 39.4%, χ2[1]=5.7; p=.017), and lower childhood household socioeconomic level (-0.410 vs. -0.045, t[185.0]=3.1; p=.002), but controlling for these factors did not affect results. Trajectories of cognitive aging in different abilities are similar in Latino and non-Latino individuals of equivalent age, education, and race. (JINS, 2016, 22, 58-65).

Cognitive Aging Trajectories and Burdens of Disability, Hospitalization and Nursing Home Admission Among Community-living Older Persons.

The course of cognitive aging has demonstrated substantial heterogeneity. This study attempted to identify distinctive cognitive trajectories and examine their relationship with burdens of disability, hospitalization, and nursing home admission. Seven hundred and fifty-four community-living persons aged 70 years or older in the Yale Precipitating Events Project were assessed with the Mini-Mental State Examination every 18 months for up to 108 months. A group-based trajectory model was used to determine cognitive aging trajectories while adjusting for age, sex, and education. Cumulative burden of disabilities, hospitalizations, and nursing home admissions over 141 months associated with the cognitive trajectories were evaluated using a generalized estimating equation Poisson model. Five distinct cognitive trajectories were identified, with about a third of participants starting with high baseline cognitive function and demonstrating No decline during the follow-up period. The remaining participants diverged with Minimal (prevalence 41%), Moderate (16%), Progressive (8%), and Rapid (3%) cognitive decline. Participants with No decline incurred the lowest incidence rates (per 1,000 person-months) of disability in activities of daily living (ADL; 75, 95% confidence intervals: 60-95) and instrumental ADL (492, 453-535), hospitalization (29, 26-33) and nursing home admission (18, 12-27), whereas participants on the Rapid trajectory experienced the greatest burden of ADL disability (612, 595-758) and those on the Progressive trajectory had the highest nursing home admission (363, 292-451). Community-living older persons follow distinct cognitive aging trajectories and experience increasing burdens of disability, hospitalization, and nursing home placement as they age, with greater burdens for those on a declining cognitive trajectory.

Predictors of Retest Effects in a Longitudinal Study of Cognitive Aging in a Diverse Community-Based Sample.

Better performance due to repeated testing can bias long-term trajectories of cognitive aging and correlates of change. We examined whether retest effects differ as a function of individual differences pertinent to cognitive aging: race/ethnicity, age, sex, language, years of education, literacy, and dementia risk factors including apolipoprotein E ε4 status, baseline cognitive performance, and cardiovascular risk. We used data from the Washington Heights-Inwood Columbia Aging Project, a community-based cohort of older adults (n=4073). We modeled cognitive change and retest effects in summary factors for general cognitive performance, memory, executive functioning, and language using multilevel models. Retest effects were parameterized in two ways, as improvement between the first and subsequent testings, and as the square root of the number of prior testings. We evaluated whether the retest effect differed by individual characteristics. The mean retest effect for general cognitive performance was 0.60 standard deviations (95% confidence interval [0.46, 0.74]), and was similar for memory, executive functioning, and language. Retest effects were greater for participants in the lowest quartile of cognitive performance (many of whom met criteria for dementia based on a study algorithm), consistent with regression to the mean. Retest did not differ by other characteristics. Retest effects are large in this community-based sample, but do not vary by demographic or dementia-related characteristics. Differential retest effects may not limit the generalizability of inferences across different groups in longitudinal research.

Developmental associations between short-term variability and long-term changes: Intraindividual correlation of positive and negative affect in daily life and cognitive aging.

Conceptual notions and empirical evidence suggest that the intraindividual correlation (iCorr) of positive affect (PA) and negative affect (NA) is a meaningful characteristic of affective functioning. PA and NA are typically negatively correlated within-person. Previous research has found that the iCorr of PA and NA is relatively stable over time within individuals, that it differs across individuals, and that a less negative iCorr is associated with better resilience and less vulnerability. However, little is known about how the iCorr of PA and NA relates to cognitive aging. This project examined how the association between PA and NA in everyday life is associated with long-term cognitive aging trajectories. To do so, we linked microlongitudinal data on PA and NA obtained on up to 33 occasions over 6 consecutive days with macrolongitudinal data on fluid and crystallized cognitive abilities obtained over 15 years from a subsample of Berlin Aging Study participants (N = 81, mean age at the microlongitudinal study = 81 years, range 73-98; 41% women). Over and above age, gender, education, overall levels of PA and NA, and number of health conditions, a less negative iCorr of PA and NA was associated with lower levels of cognitive ability and steeper cognitive declines, particularly for fluency and knowledge abilities. We discuss possible mechanisms for this finding and argue that a less negative iCorr of PA and NA may be indicative of deficits in emotional integration that are tied to changes in crystallized aspects of cognitive abilities.

Aging, Practice Effects, and Genetic Risk in the Wisconsin Registry for Alzheimer’s Prevention

Background: In the last five years, a consensus has developed that Alzheimer’s disease (AD) may begin years before overt cognitive impairment. Accordingly, the focus has shifted to identifying preclinical disease in order to match treatments to those most likely to benefit. Subtle cognitive changes, including reduced benefit from practice, may be one such preclinical sign. In this study, we explore cognitive aging trajectories within a large cohort of clinically intact late middle-aged adults. Method: Longitudinal cognitive data were analyzed from 594 participants in the Wisconsin Registry for Alzheimer’s Prevention. Mixed models were used to examine trajectories, adjusting for prior exposure, and the moderation thereof by markers of dementia risk, APOE-ε4 status, and family history of AD. Results: Practice effects were observed for Verbal Learning & Memory, Working Memory, Speed & Flexibility, and Visual Learning. However, for Working Memory and Speed & Flexibility, these effects were attenuated for FH + subjects. Conclusion: Reduced practice effects have previously been observed in clinical groups. These results in middle-aged adults suggest that they may also indicate preclinical changes on the path to AD.

Residual decline in cognition after adjustment for common neuropathologic conditions.

Neurodegenerative and cerebrovascular conditions are common in old age and are associated with cognitive decline. However, considerable heterogeneity remains in residual decline (i.e., person-specific trajectories of cognitive decline adjusted for these common neuropathologic conditions). The present study aimed to characterize profiles of residual decline in late life cognition. Up to 19 waves of longitudinal cognitive data were collected from 876 autopsied participants from 2 ongoing clinical-pathologic cohort studies of aging. Uniform neuropathologic examinations quantified measures of Alzheimer's disease, cerebral infarcts, Lewy body disease, and hippocampal sclerosis. Random effects mixture models characterized latent profiles of residual decline in global cognition. We identified 4 latent groups, and each group demonstrated distinct residual decline profiles. On average, 44% of the participants had little or no decline, 35% showed moderate decline, 13% showed severe decline and the rest (8%) had substantial within-subject fluctuation of longitudinal cognitive measures. These latent groups differed in psychological, experiential and neurobiologic factors that have been previously shown to be associated with cognitive decline. Specifically, compared with nondecliners, decliners had more depressive symptoms, were more socially isolated; were less engaged in cognitive or physical activities; and had lower density of noradrenergic neurons in locus ceruleus. After controlling for common dementia related pathologies, considerable residual variability remains in cognitive aging trajectories and this variability is not random but rather is related to markers of cognitive and neural reserve. The mixture modeling approach provides a powerful tool to identify latent groups with distinct cognitive trajectories.

Multiparity-induced enhancement of hippocampal neurogenesis and spatial memory depends on ovarian hormone status in middle age

Menopause is associated with cognitive decline, and previous parity can increase or delay the trajectory of cognitive aging. Furthermore, parity enables the hippocampus to respond to estrogens in middle age. The present study investigated how previous parity and estrogens influence cognition, neurogenesis, and neuronal activation in response to memory retrieval in the hippocampus of middle-aged females. Multiparous and nulliparous rats were ovariectomized (OVX) or received sham surgery and were treated with vehicle, 17β-estradiol, 17α-estradiol, or estrone. Rats were trained on the spatial working and reference memory versions of the Morris water maze. Multiparous rats had a significantly greater density of immature neurons in the hippocampus, enhanced acquisition of working memory, but poorer reference memory compared with nulliparous rats. Furthermore, OVX increased, while treatment with estrogens reduced, the density of immature neurons, regardless of parity. OVX improved reference memory only in nulliparous rats. Thus, motherhood has long-lasting effects on the neuroplasticity and function of the hippocampus. These findings have wide-ranging implications for the treatment of age-associated decline in women.

Conscientiousness, dementia related pathology, and trajectories of cognitive aging.

The study aim was to determine the contribution of dementia related pathologies to the association of conscientiousness with late-life cognitive health. At enrollment in 2 longitudinal clinical-pathologic cohort studies, 309 older individuals without cognitive impairment completed a standard conscientiousness measure. Annually thereafter, they completed a battery of 17 cognitive tests. On death, they underwent a uniform neuropathologic examination from which measures of neurofibrillary tangles, Lewy bodies, chronic gross cerebral infarction, and hippocampal sclerosis were derived. The relation of conscientiousness and the neuropathologic markers to cognitive decline was assessed in mixed-effects change point models to accommodate nonlinear cognitive decline. During a mean of 10.7 years of follow-up, annual decline on a composite measure of global cognition (baseline M = 0.082, SD = 0.499) was gradual (estimated M = -0.036, 95% CI [-0.046, -0.025]) until a mean of 3.2 years before death (95% CI [-3.6, -2.8]) when it accelerated to a mean annual loss of 0.369 unit (95% CI [-0.426, -0.317]), a tenfold increase. Higher conscientiousness (baseline M = 33.6, SD = 5.1) was associated with slower terminal decline (estimate = 0.064, 95% CI [0.024, 0.103]) but not preterminal decline (estimate = 0.005, 95% CI [-0.003, 0.013]). After adjustment for neuropathologic burden, conscientiousness was still related to terminal decline (estimate = 0.057, 95% CI [0.019, 0.094]) and accounted for 4% of the variance in terminal slopes. In addition, the association of neocortical Lewy bodies with terminal cognitive decline was attenuated in those with higher conscientiousness. The results suggest that higher conscientiousness is protective of late-life cognitive health.

The effects of long-term resistance exercise on the relationship between neurocognitive performance and GH, IGF-1, and homocysteine levels in the elderly

This study aimed to investigate the effects of a long-term resistance exercise intervention on executive functions in healthy elderly males, and to further understand the potential neurophysiological mechanisms mediating the changes. The study assessed forty-eight healthy elderly males randomly assigned to exercise (n = 24) or control (n = 24) groups. The assessment included neuropsychological and neuroelectric measures during a variant of the oddball task paradigm, as well as growth hormone (GH), insulin-like growth factor-1 (IGF-1), and homocysteine levels at baseline and after either a 12 month intervention of resistance exercise training or control period. The results showed that the control group had a significantly lower accuracy rate and smaller P3a and P3b amplitudes in the oddball condition after 12 months. The exercise group exhibited improved reaction times (RTs), sustained P3a and P3b amplitudes, increased levels of serum IGF-1, and decreased levels of serum homocysteine. The changes in IGF-1 levels were significantly correlated with the changes in RT and P3b amplitude of the oddball condition in the exercise group. In conclusion, significantly enhanced serum IGF-1 levels after 12 months of resistance exercise were inversely correlated with neurocognitive decline in the elderly. These findings suggest that regular resistance exercise might be a promising strategy to attenuate the trajectory of cognitive aging in healthy elderly individuals, possibly mediated by IGF-1.

Trajectories of age-related cognitive decline and potential associated factors of cognitive function in senior citizens of Beijing.

With a longer life expectancy and an increased prevalence of neurodegenerative diseases, investigations on trajectories of cognitive aging have become exciting and promising. This study aimed to estimate the patterns of age-related cognitive decline and the potential associated factors of cognitive function in community-dwelling residents of Beijing, China. In this study, 1248 older adults aged 52-88 years [including 175 mild cognitive impairment (MCI) subjects] completed a battery of neuropsychological scales. The personal information, including demographic information, medical history, eating habits, lifestyle regularity and leisure activities, was also collected. All cognitive function exhibited an agerelated decline in normal volunteers. Piece-wise linear fitting results suggested that performance on the Auditory Verbal Learning Test remained stable until 58 years of age and continued to decline thereafter. The decline in processing speed and executive function began during the early 50's. Scores on visual-spatial and language tests declined after 66 years of age. The decline stage of the general mental status ranged from 63 to 70 years of age. However, the MCI group did not exhibit an obvious age-related decline in most cognitive tests. Multivariate linear regression analyses indicated that education, gender, leisure activities, diabetes and eating habits were associated with cognitive abilities. These results indicated various trajectories of age-related decline across multiple cognitive domains. We also found different patterns of agerelated cognitive decline between MCI and normal elderly. These findings could help improve the guidance of cognitive intervention program and have implications for public policy issues.

Interleukin-6, age, and corpus callosum integrity.

The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories.

Early Life Development in a Multiethnic Sample and the Relation to Late Life Cognition

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. 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. 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. 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.

Cognitive Aging and Rate of Hospitalization in an Urban Population of Older People

The association of age-related cognitive change with hospitalization is not well understood. At 3-year intervals for a mean of 8.7 years, 2,273 older residents of a geographically defined urban community underwent cognitive testing from which a global measure was derived. Hospitalization data were obtained from Part A Medicare beneficiary records. The association of level of cognitive function and rate of cognitive decline in each 3-year interval with subsequent rate of hospitalization was assessed using mixed-effects count regression models. There were 9,091 hospitalizations involving 1,810 of the 2,273 individuals in the cohort (79.6%). Rate of hospitalization increased by 9.7% (95% confidence interval [CI]: 7.2, 12.3) with each additional study year; by 32.7% (95% CI: 26.8, 38.0) for each 1 point lower on the global cognitive measure at the beginning of an observation interval; and by 24.3% (95% CI: 16.6, 32.6) for each 1-point decrease in the global cognitive measure during the previous observation period. These associations persisted after adjustment for comorbidities and exclusion of those with a Mini-Mental State Examination score less than 26. Individual differences in trajectories of cognitive aging are associated with subsequent risk of hospitalization.

OP42 Lifecourse Socioeconomic Position and Cognitive Function in Later Life in Central and Eastern Europe: Preliminary Findings from the Hapiee Study

BackgroundSocioeconomic position (SEP) across the lifecourse is positively associated with cognitive function in later life in studies of Western populations, with later SEP likely mediating the effect of early life...

Does cognitive reserve shape cognitive decline?

Cognitive reserve is associated with a lower risk of dementia, but the extent to which it shapes cognitive aging trajectories remains unclear. Our objective is to examine the impact of 3 markers of reserve from different points in the life course on cognitive function and decline in late adulthood. Data are from 5,234 men and 2,220 women, mean age 56 years (standard deviation = 6) at baseline, from the Whitehall II cohort study. Memory, reasoning, vocabulary, and phonemic and semantic fluency were assessed 3× over 10 years. Linear mixed models were used to assess the association between markers of reserve (height, education, and occupation) and cognitive decline, using the 5 cognitive tests and a global cognitive score composed of these tests. All 3 reserve measures were associated with baseline cognitive function; the strongest associations were with occupation and the weakest with height. All cognitive functions except vocabulary declined over the 10-year follow-up period. On the global cognitive test, there was greater decline in the high occupation group (-0.27; 95% confidence interval [CI], -0.28 to -0.26) compared to the intermediate (-0.23; 95% CI, -0.25 to -0.22) and low groups (-0.21; 95% CI, -0.24 to -0.19); p = 0.001. The decline in reserve groups defined by education (p = 0.82) and height (p = 0.55) was similar. Cognitive performance over the adult life course was remarkably higher in the high reserve groups. However, rate of cognitive decline did not differ between reserve groups with the exception of occupation, where there was some evidence of greater decline in the high occupation group.

Divergent Trajectories of Physical, Cognitive, and Psychosocial Aging in Schizophrenia

Aging is not a uniform process. In the general population, there is a paradox of aging: age-associated decline in physical and some cognitive functions stands in contrast to an enhancement of subjective quality of life and psychosocial functioning. This paradox is even more striking in people with schizophrenia. Compared with the overall population, individuals with schizophrenia have accelerated physical aging (with increased and premature medical comorbidity and mortality) but a normal rate of cognitive aging, although with mild cognitive impairment starting from premorbid period and persisting throughout life. Remarkably, psychosocial function improves with age, with diminished psychotic symptoms, reduced psychiatric relapses requiring hospitalization and better self-management. Many older adults with schizophrenia successfully adapt to the illness, with increased use of positive coping techniques, enhanced self-esteem and increased social support. Although complete remission is uncommon, most individuals with schizophrenia experience significant improvement in their quality of well-being. Cohort effect and survivor bias may provide a partial explanation for this phenomenon. However, the improvement also may reflect some brain changes that are beneficial for the course of schizophrenia along with neuroplasticity of aging. The proposed hypothesis has several implications. As significant medical morbidity in schizophrenia takes years to develop, studies of changes in sensitive biomarkers of aging during the course of illness may point to new treatments aimed at normalizing the rate of biological aging in schizophrenia. At the same time, effective psychotherapeutic interventions can affect brain structure and function and produce lasting positive behavioral changes in aging adults with schizophrenia.

Reducing case ascertainment costs in U.S. population studies of Alzheimer’s disease, dementia, and cognitive impairment—Part 2

Dementia of the Alzheimer’s type (DAT) is a major public health threat in developed countries where longevity has been extended to the eighth decade of life. Estimates of prevalence and incidence of DAT vary with what is measured, be it change from a baseline cognitive state or a clinical diagnostic endpoint, such as Alzheimer’s disease. Judgment of what is psychometrically “normal” at the age of 80 years implicitly condones a decline from what is normal at the age of 30. However, because cognitive aging is very heterogeneous, it is reasonable to ask “Is ‘normal for age’ good enough to screen for DAT or its earlier precursors of cognitive impairment?” Cost containment and accessibility of ascertainment methods are enhanced by well-validated and reliable methods such as screening for cognitive impairment by telephone interviews. However, focused assessment of episodic memory, the key symptom associated with DAT, might be more effective at distinguishing normal from abnormal cognitive aging trajectories. Alternatively, the futuristic “Smart Home,” outfitted with unobtrusive sensors and data storage devices, permits the moment-to-moment recording of activities so that changes that constitute risk for DAT can be identified before the emergence of symptoms.

Longitudinal Influences of Partner Depression on Cognitive Functioning in Latino Spousal Pairs

Background/Aims: While social factors may influence the trajectories of cognitive aging, the influence of spousal characteristics (i.e. health or mental health) on cognitive decline has received little attention. This study examined the influence of baseline depressive symptoms in one spouse on cognitive functioning in the other. Methods: We conducted a longitudinal study of 279 Latino spousal pairs (558 people) taken from a cohort study (n = 1,789) in California’s central valley with assessments every 12–18 months. Results: Higher husband baseline depression was significantly associated with lower cognitive scores maintained across time for both husbands (p < 0.001) and wives (p = 0.01). Wives with higher baseline depression scores showed significantly worse cognitive function over time (p = 0.007). Conclusions: Husbands’ cognitive function was more strongly linked to their own level of depression, whereas wives’ cognitive function was influenced by both their own and their partners’ level of baseline depression. Our study further documents the public health significance of depression and our need to look beyond the individual to the reverberating effects of depression on the family.

The role of occupational complexity in trajectories of cognitive aging before and after retirement.

We examined the association between complexity of the main lifetime occupation and changes in cognitive ability in later life. Data on complexity of work with data, people, and things and on 4 cognitive factors (verbal, spatial, memory, and speed) were available from 462 individuals in the longitudinal Swedish Adoption/Twin Study of Aging. Mean age at the first measurement wave was 64.3 years (SD = 7.2), and 65% of the sample had participated in at least three waves of data collection. Occupational complexity with people and data were both correlated with cognitive performance. Individuals with more complex work demonstrated higher mean performance on the verbal, spatial, and speed factors. Latent growth curve analyses indicated that, after correcting for education, only complexity with people was associated with differences in cognitive performance and rate of cognitive change. Continued engagement as a result of occupational complexity with people helped to facilitate verbal function before retirement, whereas a previous high level of complexity of work with people was associated with faster decline after retirement on the spatial factor.