Aging is associated with disruptions in the resting-state functional architecture of the brain. Previous studies have primarily focused on age-related declines in the default mode network (DMN) and ...its implications in Alzheimer's disease. However, due to mixed findings, it is unclear if changes in resting-state network functional connectivity are linked to cognitive decline in healthy older adults. In the present study, we evaluated the influence of intra-network coherence for four higher-order cognitive resting-state networks on a sensitive measure of cognitive aging (i.e., NIH Toolbox Fluid Cognition Battery) in 154 healthy older adults with a mean age of 71 and education ranging between 12 years and 21 years (mean = 16). Only coherence within the cingulo-opercular network (CON) was significantly related to Fluid Cognition Composite scores, explaining more variance in scores than age and education. Furthermore, we mapped CON connectivity onto fluid cognitive subdomains that typically decline in advanced age. Greater CON connectivity was associated with better performance on episodic memory, attention, and executive function tasks. Overall, the present study provides evidence to propose CON coherence as a potential novel neural marker for nonpathological cognitive aging.
Older adults are at a greater risk for contracting and experiencing severe illness from COVID-19 and may be further affected by pandemic-related precautions (e.g., social distancing and isolation in ...quarantine). However, the longitudinal impact of the COVID-19 pandemic on older adults is unclear. The current study examines changes in health behaviors, psychosocial factors, and cognitive functioning in a large sample of older adults using a pre-pandemic baseline and longitudinal follow-up throughout 9 months of the COVID-19 pandemic.
One hundred and eighty-nine older adults (ages 65-89) were recruited from a multisite clinical trial to complete additional virtual assessments during the COVID-19 pandemic. Mixed effects models evaluated changes in health behaviors, psychosocial factors, and cognitive functioning during the pandemic compared to a pre-pandemic baseline and over the course of the pandemic (i.e., comparing the first and last COVID-19 timepoints).
Compared to their pre-pandemic baseline, during the pandemic, older adults reported worsened sleep quality, perceived physical health and functioning, mental health, slight increases in depression and apathy symptoms, reduced social engagement/perceived social support, but demonstrated better performance on objective cognitive tasks of attention and working memory. Throughout the course of the pandemic, these older adults reported continued worsening of perceived physical health and function, fewer depression symptoms, and they demonstrated improved cognitive performance. It is important to note that changes on self-report mood measures and cognitive performance were relatively small regarding clinical significance. Education largely served as a protective factor, such that greater years of education was generally associated with better outcomes across domains.
The present study provides insights into the longitudinal impact of the COVID-19 pandemic on health behaviors, psychosocial factors, and cognitive functioning in a population disproportionately affected by the virus. Replicating this study design in a demographically representative older adult sample is warranted to further inform intervention strategies targeting older adults negatively impacted by the COVID-19 pandemic.
Hippocampal volume is particularly sensitive to the accumulation of total brain white matter hyperintensity volume (WMH) in aging, but how the regional distribution of WMH volume differentially ...impacts the hippocampus has been less studied. In a cohort of 194 healthy older adults ages 50-89, we used a multivariate statistical method, the Scaled Subprofile Model (SSM), to (1) identify patterns of regional WMH differences related to left and right hippocampal volumes, (2) examine associations between the multimodal neuroimaging covariance patterns and demographic characteristics, and (3) investigate the relation of the patterns to subjective and objective memory in healthy aging. We established network covariance patterns of regional WMH volume differences associated with greater left and right hippocampal volumes, which were characterized by reductions in left temporal and right parietal WMH volumes and relative increases in bilateral occipital WMH volumes. Additionally, we observed lower expression of these hippocampal-related regional WMH patterns were significantly associated with increasing age and greater subjective memory complaints, but not objective memory performance in this healthy older adult cohort. Our findings indicate that, in cognitively healthy older adults, left and right hippocampal volume reductions were associated with differences in the regional distribution of WMH volumes, which were exacerbated by advancing age and related to greater subjective memory complaints. Multivariate network analyses, like SSM, may help elucidate important early effects of regional WMH volume on brain and cognitive aging in healthy older adults.
Subjective memory complaints (SMCs) may be an important early indicator of cognitive aging and preclinical Alzheimer’s disease risk. This study investigated whether age-related differences in right ...or left hippocampal volume underlie SMCs, if these relationships differ by hypertension status, and how they are related to objective memory performance in a group of 190 healthy older adults, 50–89 years of age. Analyses revealed a significant mediation of the relationship between age and mild SMCs by right hippocampal volume that was moderated by hypertension status. This moderated mediation effect was not observed with left hippocampal volume. Additionally, a moderated serial mediation model showed that age predicted right hippocampal volume, which predicted SMCs, and in turn predicted objective memory performance on several measures of verbal selective reminding in individuals with hypertension, but not in non-hypertensives. Together, these findings suggest that even mild SMCs, in the context of hypertension, provide an early indicator of cognitive aging, reflecting a potential link among vascular risk, SMCs, and the preclinical risk for Alzheimer’s disease.
•Age-related memory complaints in hypertensives are mediated by right hippocampal volume.•Mild memory concerns have a neuroanatomical basis leading to overt memory difficulties.•Mild memory complaints with hypertension may be an early marker of cognitive aging.•Aging with hypertension and memory concerns may lead to greater preclinical AD risk.
: The association between hippocampal volume and memory is continuing to be characterized in healthy older adults. Prior research suggests smaller hippocampal volume in healthy older adults is ...associated with poorer episodic memory and processing speed, as well as working memory, verbal learning, and executive functioning as measured by the NIH Toolbox Fluid (Fluid Cognition Composite, FCC) and Crystalized Cognition Composites (CCC). This study aimed to replicate these findings and to evaluate the association between: (1) hippocampal asymmetry index and cognition; and (2) independent contributions of the left and right hippocampal volume and cognition in a large sample of healthy older adults.
: One-hundred and eighty-three healthy older adults (M age = 71.72, SD = 5.3) received a T1-weighted sequence on a 3T scanner. Hippocampal subfields were extracted using FreeSurfer 6.0 and combined to provide left, right, and total hippocampal volumes. FCC subtests include Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, List Sorting, Picture Sequence Memory, and Pattern Comparison. CCC subtests include Picture Vocabulary and Oral Reading Recognition. Multiple linear regressions were performed predicting cognition composites from the total, left and right, and asymmetry of hippocampal volume, controlling for sex, education, scanner, and total intracranial volume. Multiple comparisons in primary analyses were corrected using a false discovery rate (FDR) of
< 0.05.
: FCC scores were positively associated with total (
= 0.226, FDR
= 0.044) and left (
= 0.257, FDR
= 0.024) hippocampal volume. Within FCC, Picture Sequence Memory scores positively associated with total (
= 0.284,
= 0.001) and left (
= 0.98,
= 0.001) hippocampal volume. List Sorting scores were also positively associated with left hippocampal volume (
= 0.189,
= 0.029).
: These results confirm previous research suggesting that bilateral hippocampal volume is associated with FCC, namely episodic memory. The present study also suggests the left hippocampal volume may be more broadly associated with both episodic and working memory. Studies should continue to investigate lateralized hippocampal contributions to aging processes to better identify predictors of cognitive decline.
While total white matter hyperintensity (WMH) volume on magnetic resonance imaging (MRI) has been associated with hippocampal atrophy, less is known about how the regional distribution of WMH volume ...may differentially affect the hippocampus in healthy aging. Additionally, apolipoprotein E (APOE) ε4 carriers may be at an increased risk for greater WMH volumes and hippocampal atrophy in aging. The present study sought to investigate whether regional WMH volume mediates the relationship between age and hippocampal volume and if this association is moderated by APOE ε4 status in a group of 190 cognitively healthy adults (APOE ε4 status carrier/non‐carrier = 59/131), ages 50–89. Analyses revealed that temporal lobe WMH volume significantly mediated the relationship between age and average bilateral hippocampal volume, and this effect was moderated by APOE ε4 status (−0.020 (SE = 0.009), 95% CI, −0.039, −0.003). APOE ε4 carriers, but not non‐carriers, showed negative indirect effects of age on hippocampal volume through temporal lobe WMH volume (APOE ε4 carriers: −0.016 (SE = 0.007), 95% CI, −0.030, −0.003; APOE ε4 non‐carriers: .005 (SE = 0.006), 95% CI, −0.006, 0.017). These findings remained significant after additionally adjusting for sex, years of education, hypertension status and duration, cholesterol status, diabetes status, Body Mass Index, history of smoking, and the Wechsler Adult Intelligence Scale‐IV Full Scale IQ. There were no significant moderated mediation effects for frontal, parietal, and occipital lobe WMH volumes, with or without covariates. Our findings indicate that in cognitively healthy older adults, elevated WMH volume regionally localized to the temporal lobes in APOE ε4 carriers is associated with reduced hippocampal volume, suggesting greater vulnerability to brain aging and the risk for Alzheimer's disease.
Abstract
Objective
Difficulties managing medications, particularly among older adults experiencing cognitive deficits, is an important contributing factor to medication nonadherence that may have ...significant negative financial and health outcomes. The current study examined the performance of healthy older adults’ (HOA) and individuals with amnestic mild cognitive impairment (aMCI) on the medication management abilities assessment’s (MMAA, a performance-based measure of medication management) original scoring criteria and derived error process measures, assessing medication overtaking and undertaking magnitude. Exploratory correlations between performances on the MMAA and self-reported confidence in medication management skills and cognitive abilities were also examined.
Method
A sample of 25 HOAs with aMCI and 25 age- and education-matched HOAs completed the MMAA, a self-reported medication management confidence rating and a battery of neuropsychological tests.
Results
HOAs performed significantly better on the MMAA score and committed significantly less process errors than individuals with aMCI. Despite these differences in MMAA performance, the HOA and aMCI groups rated similar high levels of confidence in their ability to manage a new medication routine. Notably, while the HOA group’s performance on all of the MMAA measures did not relate to cognitive measures, the aMCI group’s performance on the MMAA score was significantly related to memory and executive functioning and a new process error score for overtaking was related to processing speed.
Conclusions
Although these results present promising potential for the MMAA as a measure of medication management in a clinical setting, further studies need to examine the validity of the MMAA against real-world adherence measures.
Cerebral white matter (WM) lesion load, as measured by white matter hyperintensity (WMH) volume with magnetic resonance imaging (MRI), has been associated with increasing age and cardiovascular risk ...factors, like hypertension. Physical sports activity (PSA) may play an important role in maintaining WM in the context of healthy aging. In 196 healthy older adults, we investigated whether participants reporting high levels of PSA (
= 36) had reduced total and regional WMH volumes compared to those reporting low levels of PSA (
= 160). Age group young-old (YO) = 50-69 years; old-old (OO) = 70-89 years, PSA group, and age by PSA group interaction effects were tested, with sex, hypertension, and body mass index (BMI) as covariates. We found significant main effects for age group and age by PSA group interactions for total, frontal, temporal, and parietal WMH volumes. There were no main effects of PSA group on WMH volumes. The OO group with low PSA had greater total, frontal, temporal, and parietal WMH volumes than the YO with low PSA and OO with high PSA groups. WMH volumes for the YO and OO groups with high PSA were comparable. These findings indicate an age group difference in those with low PSA, with greater WMH volumes in older adults, which was not observed in those with high PSA. The results suggest that engaging in high levels of PSA may be an important lifestyle factor that can help to diminish WMH lesion load in old age, potentially reducing the impact of brain aging.
Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, ...switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65-88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = -0.18, FDR-
= 0.02; right β = -0.20, FDR-
= 0.01) and right medial orbitofrontal (β = -0.17, FDR-
= 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = -0.21, FDR-
= 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function.
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