Research and theory have shown a link between heart rate reactivity during cognitive testing and extraversion in younger adults; however, similar work has not been conducted with older adults. This ...study was designed to explore age and extraversion-related differences in within-person heart rate (HR) reactivity during two working memory tasks of varying difficulty using a multi-level modeling approach. Across 570 total within-person assessments of continuous HR monitoring, 28 younger adults (M = 19.76, SD = 1.15) and 29 older adults (M = 71.19, SD = 6.63) were administered two working memory tasks (backward digit span and n-back). There were no age differences in reactivity during the backward digit span. However, similar to previous findings, on the more difficult n-back task, younger adults low in extraversion showed a trend toward higher HR reactivity than young adults high in extraversion. Interestingly, the older adults showed the opposite pattern in that lower extraversion older adults were less reactive than the higher extraversion older adults who showed the steepest increase in HR. The HR increase of the older adults high in extraversion may be an indication of higher engagement in this more difficult task. Individual differences in extraversion need to be taken into account when administering working memory tasks in older adults.
To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk.
We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. ...Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk.
UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset.
Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD.
We examined age differences in the effort required to perform the basic cognitive operations needed to achieve a specified objective outcome, and how hypothesized increases in effort requirements in ...later life are related to intrinsic motivation associated with enjoyment of and participation in effortful cognitive activities. Young (N = 59; 20-40 years) and older (N = 57; 64-85 years) adults performed a memory-search task varying in difficulty across trials, with systolic blood pressure responsivity-calculated as the increase over baseline during task performance-used as a measure of effort expenditure and task engagement. Consistent with expectations, older adults exhibited greater levels of responsivity (i.e., effort) at all levels of objective task difficulty, and this increase was reflected in subjective perceptions of difficulty. Older adults also exhibited greater levels of disengagement (i.e., effort withdrawal) than younger adults at higher levels of task difficulty, conceivably reflecting the disproportionately greater effort required for successful performance in the former group. We also found that, relative to younger adults, older adults' engagement was more sensitive to the importance attached to the task (i.e., motivation to do well). Finally, we also obtained evidence that increased costs associated with cognitive engagement in later life were negatively associated with intrinsic levels of motivation to engage in effortful cognitive activity. The results support the general conclusion that the costs of cognitive activity increase with age in adulthood, and that these costs influence individuals' willingness to engage resources in support of demanding cognitive activities.
•Cortisol measures were aggregated over 10days (7 samples per day).•More positive CAR slopes were significantly related to better episodic memory.•Higher waking cortisol was significantly related to ...better working memory.•Diurnal cortisol output and linear slope were not related to cognition.•The relationship between the CAR and cognition did not depend upon age.
Although the hippocampus is thought to play a central role in the regulation of the cortisol awakening response (CAR), results from past studies examining the relationship between the CAR and hippocampal-mediated memory and cognition have been mixed. Inconsistent findings may be due to the use of cortisol samples collected on only 1–2days since reduced sampling can permit unstable situational factors to bias results. We used cortisol assessments from 10 consecutive days to test the relationship of the CAR to episodic memory, working memory, and processing speed in a sample of healthy young, middle-aged, and older adults (age range: 23–79years; N=56). We tested if the relationship between the CAR and cognition would depend upon age and also tested if other cortisol measures, specifically waking cortisol, diurnal cortisol output (i.e., area under the curve) and diurnal cortisol slope (linear and quadratic), would be related to cognition. We found that a more positive CAR slope was related to better episodic memory and that this relationship did not depend upon age. The CAR was not significantly related to working memory. The relationship of the CAR to processing speed was not significant when using a CAR measure that corrected for non-compliant cortisol sampling. We also found that higher waking cortisol was significantly related to better working memory, but not episodic memory or processing speed. Neither diurnal cortisol output nor diurnal linear cortisol slope was significantly related to cognitive functioning. Future work should investigate the mechanisms underpinning the relationship of the cortisol awakening process to cognitive functioning.
We tested the hypothesis that aging is associated with an increase in the effort and costs associated with cognitive activity using systolic blood pressure (SBP) as a measure of effort.
Younger and ...older adults engaged in an initial task (Phase 1) for 5 min that was relatively low (adding single digits) or high (subtracting by 3 s) in cognitive demands. They then solved a series of multiplication problems for 3 min (Phase 2). Cardiovascular measures were collected throughout, and reactivity was examined as a function of age, initial task difficulty, and test phase.
Older adults exhibited higher levels of reactivity than younger adults to cognitive engagement, with reactivity increasing with task difficulty. Difficulty of the initial task was also associated with greater effort and lower performance on the subsequent multiplication task, suggestive of fatigue or depletion. These fatigue effects were stronger for older adults.
The results were consistent with expectations and provided support for the utility of SBP reactivity as a measure of cognitive effort in studies of aging.
Insulin resistance (IR) and type 2 diabetes have been found to increase the risk for Alzheimer's clinical syndrome in epidemiologic studies but have not been associated with tau tangles in ...neuropathological research and have been inconsistently associated with cerebrospinal fluid P-tau181. IR and type 2 diabetes are well-recognized vascular risk factors. Some studies suggest that cardiovascular risk may act synergistically with cortical amyloid to increase tau measured using tau PET. Utilizing data from largely nondemented middle-aged and older adult cohorts enriched for AD risk, we investigated the association of IR and diabetes to tau PET and whether amyloid moderated those relationships.
Participants were enrolled in either the Wisconsin Registry for Alzheimer's Prevention (WRAP) or Wisconsin Alzheimer's Disease Research Center (WI-ADRC) Clinical Core. Two partially overlapping samples were studied: a sample characterized using HOMA-IR (n=280 WRAP participants) and a sample characterized on diabetic status (n=285 WRAP and n=109 WI-ADRC). IR was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Tau PET employing the radioligand
F-MK-6240 was used to detect AD-specific aggregated tau. Linear regression tested the relationship of IR and diabetic status to tau PET standardized uptake value ratio (SUVR) within the entorhinal cortex and whether relationships were moderated by amyloid assessed by amyloid PET distribution volume ratio (DVR) and amyloid PET positivity status.
Neither HOMA-IR nor diabetic status was significantly associated with tau PET SUVR. The relationship between IR and tau PET SUVR was not moderated by amyloid PET DVR or positivity status. The association between diabetic status and tau PET SUVR was not significantly moderated by amyloid PET DVR but was significantly moderated by amyloid PET positivity status. Among the amyloid PET-positive participants, the estimated marginal tau PET SUVR mean was higher in the diabetic (n=6) relative to the nondiabetic group (n=88).
Findings indicate that IR may not be related to tau in generally healthy middle-aged and older adults who are in the early stages of the AD clinicopathologic continuum but suggest the need for additional research to investigate whether a synergistic relationship between type 2 diabetes and amyloid is associated with increased tau levels.
We investigated how information search strategies used to support decision making were influenced by self-related implications of the task to the individual. Consistent with the notion of selective ...engagement, we hypothesized that increased self-relevance would result in more adaptive search behaviors and that this effect would be stronger in older adults than in younger adults.
We examined search behaviors in 79 younger and 81 older adults using a process-tracing procedure with 2 different decision tasks. The impact of motivation (i.e., self-related task implications) was examined by manipulating social accountability and the age-related relevance of the task.
Although age differences in search strategies were not great, older adults were more likely than younger adults to use simpler strategies in contexts with minimal self-implications. Contrary to expectations, young and old alike were more likely to use noncompensatory than compensatory strategies, even when engaged in systematic search, with education being the most important determinant of search behavior.
The results support the notion that older adults are adaptive decision makers and that factors other than age may be more important determinants of performance in situations where knowledge can be used to support performance.
The present study examined the day-to-day fluctuation of state-like anticipatory coping (coping employed prior to stressors) and how these coping processes relate to important outcomes for older ...adults (i.e., physical health, affect, memory failures).
Forty-three older adults aged 60-96 (M = 74.65, SD = 8.19) participated in an 8-day daily diary study of anticipatory coping, stressors, health, affect, and memory failures. Participants reported anticipatory coping behaviors on one day with respect to 6 distinct stressor domains that could occur the following day.
Multilevel models indicated that anticipatory coping changes from day to day and within stressor domains. Lagged associations suggested that yesterday's anticipatory coping for potential upcoming arguments is related to today's physical health and affect. Increased stagnant deliberation is associated with reduced cognitive reactivity (i.e., fewer memory failures) to arguments the next day.
Taken together, these findings suggest that anticipatory coping is dynamic and associated with important daily outcomes.
INTRODUCTION
A hallmark of Alzheimer's disease (AD) is the aggregation of proteins (amyloid beta A and hyperphosphorylated tau T) in the brain, making cerebrospinal fluid (CSF) proteins of particular ...interest.
METHODS
We conducted a CSF proteome‐wide analysis among participants of varying AT pathology (n = 137 participants; 915 proteins) with nine CSF biomarkers of neurodegeneration and neuroinflammation.
RESULTS
We identified 61 proteins significantly associated with the AT category (P < 5.46 × 10−5) and 636 significant protein‐biomarker associations (P < 6.07 × 10−6). Proteins from glucose and carbon metabolism pathways were enriched among amyloid‐ and tau‐associated proteins, including malate dehydrogenase and aldolase A, whose associations with tau were replicated in an independent cohort (n = 717). CSF metabolomics identified and replicated an association of succinylcarnitine with phosphorylated tau and other biomarkers.
DISCUSSION
These results implicate glucose and carbon metabolic dysregulation and increased CSF succinylcarnitine levels with amyloid and tau pathology in AD.
Highlights
Cerebrospinal fluid (CSF) proteome enriched for extracellular, neuronal, immune, and protein processing.
Glucose/carbon metabolic pathways enriched among amyloid/tau‐associated proteins.
Key glucose/carbon metabolism protein associations independently replicated.
CSF proteome outperformed other omics data in predicting amyloid/tau positivity.
CSF metabolomics identified and replicated a succinylcarnitine–phosphorylated tau association.
•Cortisol Relates to Regional Limbic System Structure in Older but not Younger Adults.•We used 7 cortisol samples per day across 10 consecutive days to measure cortisol.•The relationship of age to ...amygdalar volume depended upon cortisol output.•An Age X Cortisol Slope interaction predicted right caudal ACC thickness.•Cortisol was related to limbic system structure in older but not younger adults.
We investigated if the relationship between age and regional limbic system brain structure would be moderated by diurnal cortisol output and diurnal cortisol slope. Participants aged 23–83 years collected seven salivary cortisol samples each day for 10 consecutive days and underwent magnetic resonance imaging. Age, sex, cortisol, and an age x cortisol interaction were tested as predictors of hippocampal and amygdalar volume and caudal and rostral anterior cingulate cortex (ACC) thickness. We found significant interactions between age and cortisol on left and right amygdalar volumes and right caudal ACC thickness. Older adults with higher cortisol output had smaller left and right amygdalar volumes than older adults with lower cortisol output and younger adults with higher cortisol output. Older and younger adults with lower cortisol output had similar amygdalar volumes. Older adults with a steeper decline in diurnal cortisol had a thicker right caudal ACC than younger adults with a similarly shaped cortisol slope. Hippocampal volume was not related to either cortisol slope or output, nor was pallidum volume which was assessed as an extra-limbic control region. Results suggest that subtle differences in cortisol output are related to differences in limbic system structure in older but not younger adults.
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