Objectives
To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health‐related, and genetic predictors of stability or decline.
Design
...Prospective cohort study.
Setting
The Betula Project, Umeå, Sweden.
Participants
One thousand nine hundred fifty‐four healthy participants aged 35 to 85 at baseline.
Measurements
Memory was assessed according to validated episodic memory tasks in participants from a large population‐based sample. Data were analyzed using a random‐effects pattern‐mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory.
Results
Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age‐typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol‐O‐methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E ɛ4 allele was more frequent in decliners.
Conclusion
Quantitative, attrition‐corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity.
Abstract Introduction The objective was to examine whether subjective memory impairment (SMI) predicts all-cause dementia or Alzheimer's disease (AD) in a population-based study with long-term ...follow-up (median = 10 years). Methods A total of 2043 initially dementia-free participants (≥ 60 years) made three memory ratings (“compared with others”, “compared with five years ago”, and “complaints from family/friends”) at baseline. During follow-up, 372 participants developed dementia (208 with AD). Results Cox regression revealed that subjective memory impairment ratings predicted all-cause dementia in models adjusting for age and sex (hazard ratio or HR from 2.04 to 3.94), with even higher values for AD (HR from 2.29 to 5.74). The result persisted in models including other covariates, including baseline episodic memory performance, and in analyses restricted to participants with long time to dementia diagnosis (≥ 5 years). Discussion The findings underscore the usefulness of subjective memory assessment in combination with other factors in identifying individuals at risk for developing dementia.
Objectives
To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade‐long follow‐up period.
Design
Prospective cohort study.
...Setting
Betula Study, Umeå, Sweden.
Participants
A population‐based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).
Measurements
Olfactory performance using the Scandinavian Odor‐Identification Test (SOIT) and self‐reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.
Results
Within the 10‐year follow‐up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71–0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health‐related and cognitive variables (HR = 0.92, 95% CI = 0.87–0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87–0.97, P = .001). Similar results were obtained for self‐reported olfactory dysfunction.
Conclusion
Poor odor identification and poor self‐reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.
To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance ...on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.
Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal ...approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.
Five-year changes in episodic and semantic memory were examined in a sample of 829 participants (35-80 years). A cohort-matched sample (
N
= 967) was assessed to control for practice effects. For ...episodic memory, cross-sectional analyses indicated gradual age-related decrements, whereas the longitudinal data revealed no decrements before age 60, even when practice effects were adjusted for. Longitudinally, semantic memory showed minor increments until age 55, with smaller decrements in old age as compared with episodic memory. Cohort differences in educational attainment appear to account for the discrepancies between cross-sectional and longitudinal data. Collectively, the results show that age trajectories for episodic and semantic memory differ and underscore the need to control for cohort and retest effects in cross-sectional and longitudinal studies, respectively.
Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain ...networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n
=
287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior–posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to
mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
► We report causal role of WM integrity in age-related differences in processing speed. ► Age related decreases in FA and increases in MD were observed. ► The anterior section of the corpus callosum was more susceptible to aging. ► Compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging.
Some elderly appear to resist age-related decline in cognitive functions, but the neural correlates of successful cognitive aging are not well known. Here, older human participants from a ...longitudinal study were classified as successful or average relative to the mean attrition-corrected cognitive development across 15-20 years in a population-based sample (n = 1561). Fifty-one successful elderly and 51 age-matched average elderly (mean age: 68.8 years) underwent functional magnetic resonance imaging while performing an episodic memory face-name paired-associates task. Successful older participants had higher BOLD signal during encoding than average participants, notably in the bilateral PFC and the left hippocampus (HC). The HC activation of the average, but not the successful, older group was lower than that of a young reference group (n = 45, mean age: 35.3 years). HC activation was correlated with task performance, thus likely contributing to the superior memory performance of successful older participants. The frontal BOLD response pattern might reflect individual differences present from young age. Additional analyses confirmed that both the initial cognitive level and the slope of cognitive change across the longitudinal measurement period contributed to the observed group differences in BOLD signal. Further, the differences between the older groups could not be accounted for by differences in brain structure. The current results suggest that one mechanism behind successful cognitive aging might be preservation of HC function combined with a high frontal responsivity. These findings highlight sources for heterogeneity in cognitive aging and may hold useful information for cognitive intervention studies.
We examined whether conversion to dementia can be predicted by self-reported olfactory impairment and/or by an inability to identify odors. Common forms of dementia involve an impaired sense of ...smell, and poor olfactory performance predicts cognitive decline among the elderly. We followed a sample of 1529 participants, who were within a normal range of overall cognitive function at baseline, over a 10-year period during which 159 were classified as having a dementia disorder. Dementia conversion was predicted from demographic variables, Mini-Mental State Examination score, and olfactory assessments. Self-reported olfactory impairment emerged as an independent predictor of dementia. After adjusting for effects of other predictors, individuals who rated their olfactory sensitivity as "worse than normal" were more likely to convert to dementia than those who reported normal olfactory sensitivity (odds ratio OR = 2.17; 95% confidence interval CI 1.40, 3.37). Additionally, low scores on an odor identification test also predicted conversion to dementia (OR per 1 point increase = 0.89; 95% CI 0.81, 0.98), but these two effects were additive. We suggest that assessing subjective olfactory complaints might supplement other assessments when evaluating the risk of conversion to dementia. Future studies should investigate which combination of olfactory assessments is most useful in predicting dementia conversion.
Abstract Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change ...in DMN activity and connectivity. Cognitively intact participants (aged 49–79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.
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