Implications For Cognitive Aging Research Articles

H - 02 Unveiling the Effects of Bilingualism on Autobiographical Memory in Hispanics: Implications for Cognitive Aging.

Episodic autobiographical memory (EAM) may be particularly sensitive to age-related cognitive decline and risk for Alzheimer's disease. Virtually nothing is known about EAM specificity in Hispanic individuals. Bilingualism is a cognitive factor that may influence EAM specificity among Hispanics. The present study aimed to 1) examine if EAM is sensitive to age in Hispanics and 2) reveal whether bilingualism influences EAM specificity in Hispanics. A sample of 150 young and middle-aged/older adults (50 English-Spanish bilingual Hispanics; 50 monolingual English-speaking Hispanics; 50 monolingual English speaking Non-Hispanic Whites) narrated EAMs using the established Autobiographical Interview (Levine et al., 2002). Using the scoring protocol of the Autobiographical Interview, we evaluated the narratives for episodic and non-episodic detail. We replicated the often-found age-related reduction in episodic detail generation in Hispanics. Bilingual Hispanics' memories were more episodically specific than monolingual Hispanics and Non-Hispanic Whites. We also found that, among bilingual Hispanics, the language used at encoding versus language used at memory retrieval was not associated with episodic specificity. Our findings suggest that episodic autobiographical memory is sensitive to age and bilingualism in Hispanics, making it a culturally appropriate cognitive measure among this population.

A Framework for Assessing the Effects of Climate Change on Dementia Risk and Burden.

Alzheimer's disease and related dementias (ADRD) represent a public health crisis poised to worsen in a changing climate. Substantial dementia burden is modifiable, attributable to risk rooted in social and environmental conditions. Climate change threatens older populations in numerous ways, but implications for cognitive aging are poorly understood. We illuminate key mechanisms by which climate change will shape incidence and lived experiences of ADRD, and propose a framework for strengthening research, clinical, and policy actions around cognitive health in the context of climate change. Direct impacts and indirect risk pathways operating through built, social, interpersonal, and biomedical systems are highlighted. Air pollution compromises brain health directly and via systemic cardiovascular and respiratory ailments. Flooding and extreme temperatures constrain health behaviors like physical activity and sleep. Medical care resulting from climate-related health shocks imposes economic and emotional tolls on people living with dementia and caregivers. Throughout, inequitable distributions of climate-exacerbated risks and adaptive resources compound existing disparities in ADRD incidence, comorbidities, and care burden. Translational research, including work prioritizing underserved communities, is crucial. A mechanistic framework can guide research questions and methods and identify clinical- and policy-level intervention loci for prevention and mitigation of climate-related impacts on ADRD risk and burden.

Associations between social burden, perceived stress, and diurnal cortisol profiles in older adults: implications for cognitive aging

Stress can be a risk factor for mental and physical health. We investigated the role of social burden as a potential stressor in older age and its associations with cognitive aging (i.e., within the domains inhibition and cognitive flexibility of executive functioning). Eighty-three older adults (N = 38 male, mean age = 74.0 ± 5.7 years, body-mass index = 25.5 ± 4.1 kg/m2) aged 64 years or older participated. Cognitive flexibility and inhibition were assessed by means of a Trail-Making Test (TMT) and a Stroop task. Perceived levels of social burden and perceived stress in general were assessed via standardized questionnaires. Furthermore, diurnal cortisol profiles were assessed. Overall, older participants showed lower cognitive performance than the younger (both inhibition and cognitive flexibility; p < .044). However, this association did not remain significant when adjusting for multiple comparisons. Social burden was highly correlated with perceived stress, highlighting its importance as a stressor (p < .001). Furthermore, participants who reported higher levels of perceived stress showed lower performance in the TMT as a measure for cognitive flexibility (p < .001). Moreover, social burden was associated with cognitive flexibility, which was assessed by means of the TMT (p = .031). However, this association did not remain significant when using the adjusted α-level. Furthermore, we found that total diurnal cortisol output was a mediator for the relationship between age and inhibition, which was assessed by means of a Stroop task. At last, we found that the mediating role of cortisol interacts with social burden in the way that especially in younger age, high levels of social burden are associated with higher cortisol levels and, therefore, with lower cognitive performance. We conclude that it is important to consider social burden as an additional stressor in older age which is associated with cognitive aging.

Heterogeneity in longitudinal deterioration of white matter microstructural integrity in the population and its implications for cognitive aging

AbstractBackgroundWhite matter (WM) changes are widely seen in the elderly due to aging and pathological processes and have significant impact on cognitive aging. It is critical to understand the heterogeneity and drivers (causes) of the longitudinal deterioration of WM microstructural integrity, especially in a population‐based sample, to provide mechanistic insights into cognitive and brain aging.MethodLeveraging longitudinal diffusion tensor imaging (DTI) data from Mayo Clinic Study of Aging, we assessed whether individuals clustered based on distinct longitudinal fractional anisotropy (FA) trajectories. A total of 533 subjects (487 cognitively unimpaired, 62 with mild cognitive impairment and 4 with dementia diagnosis) aged ≥ 60 years and with at least two DTI scans (125 subjects had at least 3 scans) were included. To identify clusters of individuals with common FA profiles over time, we applied an in‐house longitudinal Bayesian mixed‐effects clustering analysis framework to the imaging data. Age at MRI accounted for the longitudinal component of the model, while sex and APOE4 carrier status were used as fixed effects.ResultWe identified four distinct clusters (Figure 1). We found that most WM tracts decline with age across all clusters but brainstem and association fibers were least likely to decline with aging. APOE4 carriership and amyloid deposition did not differ between the clusters. We found a resilient cluster of individuals (34%) (cluster 1) with better baseline WM and systemic vascular health who had a slower rate of cognitive and WM integrity decline over time. These individuals had highest baseline commissural and association fibers. The resilient group was in contrast to an “at risk” cluster of individuals (16%) (cluster 2) who had lower baseline WM integrity and systemic health and declined the fastest in both WM health and cognition over timeConclusionLongitudinal clustering of WM tracts provided insights into the differential aging of WM in the population which may be unrelated to Alzheimer’s disease pathophysiology. Measuring overall WM health and vulnerable tracts in the elderly can be useful as biomarkers and aid in the identification of “at risk” groups for prevention of future cognitive decline.

Relationship Between Risk Factors and Brain Reserve in Late Middle Age: Implications for Cognitive Aging

BackgroundBrain reserve can be defined as the individual variation in the brain structural characteristics that later in life are likely to modulate cognitive performance. Late midlife represents a point in aging where some structural brain imaging changes have become manifest but the effects of cognitive aging are minimal, and thus may represent an ideal opportunity to determine the relationship between risk factors and brain imaging biomarkers of reserve.ObjectiveWe aimed to assess neuroimaging measures from multiple modalities to broaden our understanding of brain reserve, and the late midlife risk factors that may make the brain vulnerable to age related cognitive disorders.MethodsWe examined multimodal [structural and diffusion Magnetic Resonance Imaging (MRI), FDG PET] neuroimaging measures in 50–65 year olds to examine the associations between risk factors (Intellectual/Physical Activity: education-occupation composite, physical, and cognitive-based activity engagement; General Health Factors: presence of cardiovascular and metabolic conditions (CMC), body mass index, hemoglobin A1c, smoking status (ever/never), CAGE Alcohol Questionnaire (>2, yes/no), Beck Depression Inventory score), brain reserve measures [Dynamic: genu corpus callosum fractional anisotropy (FA), posterior cingulate cortex FDG uptake, superior parietal cortex thickness, AD signature cortical thickness; Static: intracranial volume], and cognition (global, memory, attention, language, visuospatial) from a population-based sample. We quantified dynamic proxies of brain reserve (cortical thickness, glucose metabolism, microstructural integrity) and investigated various protective/risk factors.ResultsEducation-occupation was associated with cognition and total intracranial volume (static measure of brain reserve), but was not associated with any of the dynamic neuroimaging biomarkers. In contrast, many general health factors were associated with the dynamic neuroimaging proxies of brain reserve, while most were not associated with cognition in this late middle aged group.ConclusionBrain reserve, as exemplified by the four dynamic neuroimaging features studied here, is itself at least partly influenced by general health status in midlife, but may be largely independent of education and occupation.

Defining Cognitive Reserve and Implications for Cognitive Aging.

The aim of this review is to summarize current conceptual models of cognitive reserve (CR) and related concepts and to discuss evidence for these concepts within the context of aging and Alzheimer's disease. Evidence to date supports the notion that higher levels of CR, as measured by proxy variables reflective of lifetime experiences, are associated with better cognitive performance, and with a reduced risk of incident mild cognitive impairment/dementia. However, the impact of CR on longitudinal cognitive trajectories is unclear and may be influenced by a number of factors. Although there is promising evidence that some proxy measures of CR may influence structural brain measures, more research is needed. The protective effects of CR may provide an important mechanism for preserving cognitive function and cognitive well-being with age, in part because it can be enhanced throughout the lifespan. However, more research on the mechanisms by which CR is protective is needed.

Chapter 11 - Cognitive reserve

Cognitive reserve is a latent construct theorized to account for the discrepancy between observed brain deterioration and ultimate clinical outcomes. This review outlines the theoretical development of the reserve concept and presents major trends within epidemiological and neuroimaging research literatures in support of such a construct. Particular focus is placed on the implications for cognitive aging and dementia.

Sleep disruption explains age-related prospective memory deficits: implications for cognitive aging and intervention

ABSTRACTThe high prevalence of sleep disruption among older adults may have implications for cognitive aging, particularly for higher-order aspects of cognition. One domain where sleep disruption may contribute to age-related deficits is prospective memory—the ability to remember to perform deferred actions at the appropriate time in the future. Community-dwelling older adults (55–93 years, N = 133) undertook assessment of sleep using actigraphy and participated in a laboratory-based prospective memory task. After controlling for education, sleep disruption (longer awakenings) was associated with poorer prospective memory. Additionally, longer awakenings mediated the relationship between older age and poorer prospective memory. Other metrics of sleep disruption, including sleep efficiency and wake after sleep onset, were not related to prospective memory, suggesting that examining the features of individual wake episodes rather than total wake time may help clarify relationships between sleep and cognition. The mediating role of awakening length was partially a function of greater depression and poorer executive function (shifting) but not retrospective memory. This study is among the first to examine the association between objectively measured sleep and prospective memory in older adults. Furthermore, this study is novel in suggesting sleep disruption might contribute to age-related prospective memory deficits; perhaps, with implications for cognitive aging more broadly. Our results suggest that there may be opportunities to prevent prospective memory decline by treating sleep problems.

Nutrient intake and cerebral metabolism in healthy middle-aged adults: Implications for cognitive aging

Objectives: Growing evidence suggests dietary factors influence cognition, but the effects of nutrient intake on cerebral metabolism in adults are currently unknown. The present study investigated the relationship between major macronutrient intake (fat, carbohydrate, and protein) and cerebral neurochemical profiles in middle-aged adults.Methods: Thirty-six adults recorded dietary intake for 3 days prior to completing cognitive testing and a proton magnetic resonance spectroscopy (1H-MRS) scan. 1H-MRS of occipitoparietal gray matter was used to assess glutamate (Glu), N-acetyl-aspartate (NAA), choline (Cho), and myo-inositol (mI) relative to creatine (Cr) levels.Results: Regression analyses revealed that high intake of polyunsaturated fatty acids (PUFAs) was associated with lower cerebral Glu/Cr (P = 0.005), and high intake of saturated fat (SFA) was associated with poorer memory function (P = 0.030) independent of age, sex, education, estimated intelligence, total caloric intake, and body mass index.Discussion: In midlife, greater PUFA intake (ω-3 and ω-6) may be associated with lower cerebral glutamate, potentially indicating more efficient cellular reuptake of glutamate. SFA intake, on the other hand, was linked with poorer memory performance. These results suggest that dietary fat intake modification may be an important intervention target for the prevention of cognitive decline.

Estrogen–cholinergic interactions: Implications for cognitive aging

This article is part of a Special Issue “Estradiol and Cognition”.While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen–cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen–cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic–estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects.

Interactive effects of age and estrogen on cortical neurons: implications for cognitive aging

In the past few decades it has become clear that estrogen signaling plays a much larger role in modulating the cognitive centers of the brain than previously thought possible. We have developed a nonhuman primate (NHP) model to investigate the relationships between estradiol (E) and cognitive aging. Our studies of cyclical E treatment in ovariectomized (OVX) young and aged rhesus monkeys have revealed compelling cognitive and synaptic effects of E in the context of aging. Delayed response (DR), a task that is particularly dependent on integrity of dorsolateral prefrontal cortex (dlPFC) area 46 revealed the following: (1) that young OVX rhesus monkeys perform equally well whether treated with E or vehicle (V), and (2) that aged OVX animals given E perform as well as young adults with or without E, whereas OVX V-treated aged animals display significant DR impairment. We have analyzed the structure of layer III pyramidal cells in area 46 in these same monkeys. We found both age and treatment effects on these neurons that are consistent with behavioral data. Briefly, reconstructions of pyramidal neurons in area 46 from these monkeys showed that cyclical E increased the density of small, thin spines in both young and aged monkeys. However, this effect of E was against a background of age-related loss of small, thin spines, leaving aged V-treated monkeys with a particularly low density of these highly plastic spines, and vulnerable to cognitive decline. Our current interpretation is that E not only plays a critically important role in maintaining spine number, but also enables synaptic plasticity through a cyclical increase in small highly plastic spines that may be stabilized in the context of learning. Interestingly, recent studies demonstrate that chronic E is less effective at inducing spinogenesis than cyclical E. We have begun to link certain molecular attributes of excitatory synapses in area 46 to E effects and cognitive performance in these monkeys. Given the importance of synaptic estrogen receptor α (ER-α) in rat hippocampus, we focused our initial studies on synaptic ER-α in area 46. Three key findings have emerged from these studies: (1) synaptic ER-α is present in axospinous synapses in area 46; (2) it is stable across treatment and age groups (which is not the case in rat hippocampus); and (3) the abundance and distribution of synaptic ER-α is a key correlate of individual variation in cognitive performance in certain age and treatment groups. These findings have important implications for the design of hormone treatment strategies for both surgically and naturally menopausal women. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Region-specific genetic alterations in the aging hippocampus: implications for cognitive aging.

Aging is associated with cognitive decline in both humans and animals and of all brain regions, the hippocampus appears to be particularly vulnerable to senescence. Age-related spatial learning deficits result from alterations in hippocampal connectivity and plasticity. These changes are differentially expressed in each of the hippocampal fields known as cornu ammonis 1 (CA1), cornu ammonis 3 (CA3), and the dentate gyrus. Each sub-region displays varying degrees of susceptibility to aging. For example, the CA1 region is particularly susceptible in Alzheimer's disease while the CA3 region shows vulnerability to stress and glucocorticoids. Further, in animals, aging is the main factor associated with the decline in adult neurogenesis in the dentate gyrus. This review discusses the relationship between region-specific hippocampal connectivity, morphology, and gene expression alterations and the cognitive deficits associated with senescence. In particular, data are reviewed that illustrate how the molecular changes observed in the CA1, CA3, and dentate regions are associated with age-related learning deficits. This topic is of importance because increased understanding of how gene expression patterns reflect individual differences in cognitive performance is critical to the process of identifying new and clinically useful biomarkers for cognitive aging.

Functional neuroimaging of memory: implications for cognitive aging.

Our understanding of the ways in which changes in specific neural systems mediate adult age differences in memory is rapidly increasing, due in no small part to the advent of functional neuroimaging techniques. This article reviews age-related changes in memory performance obtained with behavioral measures, describes models of the neural mechanisms of memory, and derives predictions from these models regarding age-related changes in brain activation patterns. The neuroimaging findings obtained to date support models emphasizing the role of prefrontal cortex in age-related changes in memory functioning, especially for episodic memory retrieval. In general, neural activation associated with episodic memory encoding is regionally similar for younger and older adults but relatively lower in magnitude for older adults. During retrieval, activation that is restricted to the right prefrontal cortex for younger adults is more likely to be bilateral for older adults. Prefrontal activation exhibits an age-related increase when working memory tasks require simple storage and an age-related decrease when working memory requires higher-level executive processes. Although the evidence is limited, behavioral performance and activation patterns appear to be similar among younger and older adults on tests of semantic (context-independent) and implicit memory. We conclude that several methodological issues, such as defining the relation between brain structure and function, and determining the relationship between performance and activation, are particularly important for understanding age-related changes. Future directions for aging research include further investigation of the relation between encoding and retrieval and the identification of both spared and impaired neural systems.