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Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

ABSTRACT: Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important "signal" rather than measurement-related "noise." Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-differences (MSSD) during a digit n-back working memory (WM) task in a sample of healthy adults (aged 20-94 years; n =?171), we examined effects of aging on whole-brain 1) BOLD variability during task (mean condition MSSD across 0-2-3-4 back conditions), 2) BOLD variability modulation to incrementally increasing WM difficulty (linear slope from 0-2-3-4 back), and 3) the association of age-related differences in variability with in- and out-of-scanner WM performance. Widespread cortical and subcortical regions evidenced increased mean variability with increasing age, with no regions evidencing age-related decrease in variability. Additionally, posterior cingulate/precuneus exhibited increased variability to WM difficulty. Notably, both age-related increases in BOLD variability were associated with significantly poorer WM performance in all but the oldest adults. These findings lend support to the growing corpus suggesting that brain-signal variability is altered in healthy aging; specifically, in this adult lifespan sample, BOLD-variability increased with age and was detrimental to cognitive performance.

SUBMITTER: Boylan MA

PROVIDER: S-EPMC7727366 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

Boylan Maria A MA Foster Chris M CM Pongpipat Ekarin E EE Webb Christina E CE Rodrigue Karen M KM Kennedy Kristen M KM

Cerebral cortex (New York, N.Y. : 1991) 20210101 1

Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important "signal" rather than measurement-related "noise." Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-dif ...[more]

PMID: 32915200

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Project description:Age and apolipoprotein E (APOE) e4 genotype are two of the strongest known risk factors for sporadic Alzheimer's disease (AD). Neuroimaging has shown hemodynamic response changes with age, in asymptomatic carriers of the APOE e4 allele, and in AD. In this study, we aimed to characterize and differentiate age- and APOE gene-specific hemodynamic changes to breath-hold and visual stimulation. A further aim was to study whether these responses were modulated by 3-day intake of nitrate, a nitric oxide (NO) source. The study was designed as a randomized, double-blinded, placebo-controlled crossover study, and the study cohort comprised 41 APOE e4 carriers (e3/e4 or e4/e4 genotype) and 40 non-carriers (e3/e3 genotype) aged 30-70?years at enrollment. The participants underwent two scanning sessions, each preceded by ingestion of sodium nitrate or sodium chloride (control). During functional magnetic resonance imaging (fMRI) sessions, participants performed two concurrent tasks; a breath-hold task to probe cerebrovascular reactivity and a visual stimulation task to evoke functional hyperemia, respectively. We found that the blood oxygenation level dependent (BOLD) hemodynamic response to breath-hold was altered in APOE e4 carriers relative to non-carriers. Mid-aged (50-60?years of age) e4 carriers exhibited a significantly increased peak time relative to mid-aged e3 carriers, and peak time for younger (30-40?years of age) e4 carriers was significantly shorter than that of mid-aged e4 carriers. The response width was significantly increased for e4 carriers. The response peak magnitude significantly decreased with age. For the visual stimulation task, we found age-related changes, with reduced response magnitude with age but no significant effect of APOE allele type. We found no effect of nitrate ingestion on BOLD responses evoked by the breath-hold and visual stimulation tasks. The APOE gene-dependent response to breath-hold may reflect NO-independent differences in vascular function.

Project description:BackgroundMaintaining both walking speed and cognitive function is essential for active, healthy aging. This study investigated age-related differences in walking speed and global cognitive function with aging and the association between them among older adults residing in the developing country of China.MethodsThis cross-sectional study measured usual (UWS) and maximal walking speed (MWS) of participants for six meters. The Chinese version of the Montreal Cognitive Assessment was used to evaluate global cognition through in-person interviews. Analyses of variance were used to compare the differences in UWS, MWS, and global cognition between genders and age groups. Multiple linear regression models were used to determine the association between walking speed and global cognitive function.ResultsIn total, 791 Chinese adults (252 men and 539 women) aged 60-89 years were included in this study. Markedly slowed UWS and worse global cognitive function scores were observed for both genders among adults ≥80 years of age. MWS slowed considerably in men ≥85 years of age and in women ≥80 years of age. There was a significant gender difference in MWS-with men walking faster than women-but not in UWS. Linear regression analysis adjusted for the confounding factors of gender, height, weight, years of education, and chronic disease indicated that MWS, but not UWS, was significantly associated with global cognitive function (β = 0.086, [0.177, 1.657], P = 0.015) such that slower maximal walking speed was associated with poorer cognitive performance. This association was statistically significant only for adults aged 75-79 years (β = 0.261 [0.647, 4.592], P = 0.010).ConclusionWalking speed was slower in the older age groups. Global cognitive function deteriorated markedly after 80 years of age. After controlling for confounding variables, slower MWS, but not UWS, was associated with poorer global cognitive function. MWS may serve as a potential indicator for earlier identification of poor cognition and motoric cognitive risk syndrome in an older Chinese population.

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Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

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Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

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