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The relationship between white matter hyperintensities and cognitive reference abilities across the life span.

ABSTRACT: We examined the relationship between white matter hyperintensities (WMH) burden and performance on 4 reference abilities: episodic memory, perceptual speed, fluid reasoning, and vocabulary. Cross-sectional data of 486 healthy adults from 20 to 80 years old enrolled in an ongoing longitudinal study were analyzed. A piecewise regression across age identified an inflection point at 43 years old, where WMH total volume began to increase with age. Subsequent analyses focused on participants above that age (N = 351). WMH total volume had significant inverse correlations with perceptual speed and memory. Regional measures of WMH showed inverse correlations with all reference abilities. We performed principal component analysis of the regional WMH data to create a model of principal components regression. Parietal WMH regional volume burden mediated the relationship between age and perceptual speed in simple and multiple mediation models. The principal components regression pattern associated with perceptual speed also mediated the relationship between age and perceptual speed performance. These results across the extended adult life span help clarify the influence of WMH on cognitive aging.

SUBMITTER: Moura AR

PROVIDER: S-EPMC6901174 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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The relationship between white matter hyperintensities and cognitive reference abilities across the life span.

Moura Ana R AR Lee Seonjoo S Habeck Christian C Razlighi Qolamreza Q Stern Yaakov Y

Neurobiology of aging 20190829

We examined the relationship between white matter hyperintensities (WMH) burden and performance on 4 reference abilities: episodic memory, perceptual speed, fluid reasoning, and vocabulary. Cross-sectional data of 486 healthy adults from 20 to 80 years old enrolled in an ongoing longitudinal study were analyzed. A piecewise regression across age identified an inflection point at 43 years old, where WMH total volume began to increase with age. Subsequent analyses focused on participants above tha ...[more]

PMID: 31585365

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Project description:White matter hyperintensities (WMH) are a key hallmark of subclinical cerebrovascular disease and are known to impair cognition. Here, we parcellated WMH using a novel system that segments WMH based on both lobar regions and distance from the ventricles, dividing the brain into a coordinate system composed of 36 distinct parcels ('bullseye' parcellation), and then investigated the effect of distribution on cognition using two different analytic approaches. Data from a well characterized sample of healthy older adults (58 to 84 years) who were free of dementia were included. Cognition was evaluated using 12 computerized tasks, factored onto 4 indices representing episodic memory, speed of processing, fluid reasoning and vocabulary. We first assessed the distribution of WMH according to the bullseye parcellation and tested the relationship between WMH parcellations and performance across the four cognitive domains. Then, we used a data-driven approach to derive latent variables within the WMH distribution, and tested the relation between these latent components and cognitive function. We observed that different, well-defined cognitive constructs mapped to specific WMH distributions. Speed of processing was correlated with WMH in the frontal lobe, while in the case of episodic memory, the relationship was more ubiquitous, involving most of the parcellations. A principal components analysis revealed that the 36 bullseye regions factored onto 3 latent components representing the natural aggrupation of WMH: fronto-parietal periventricular (WMH principally in the frontal and parietal lobes and basal ganglia, especially in the periventricular region); occipital; and temporal and juxtacortical WMH (involving WMH in the temporal lobe, and at the juxtacortical region from frontal and parietal lobes). We found that fronto-parietal periventricular and temporal & juxtacortical WMH were independently associated with speed of processing and episodic memory, respectively. These results indicate that different cognitive impairment phenotypes might present with specific WMH distributions. Additionally, our study encourages future research to consider WMH classifications using parcellations systems other than periventricular and deep localizations.

Project description:It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large (N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change among cognitive factors of fluid intelligence, language, and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition.

Project description:BackgroundAlbuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain.Study designCross sectional.Setting & participantsBoston, MA, elders receiving home health services to maintain independent living who consented to brain magnetic resonance imaging.PredictorUrine albumin-creatinine ratio (ACR).OutcomePerformance on a cognitive battery assessing executive function and memory by using principal components analysis and white matter hyperintensity volume on brain imaging, evaluated in logistic and linear regression models.ResultsIn 335 participants, mean age was 73.4 +/- 8.1 years and 123 participants had microalbuminuria or macroalbuminuria. Each doubling of ACR was associated with worse executive function (beta = -0.05; P = 0.005 in univariate and beta = -0.07; P = 0.004 in multivariable analyses controlling for age, sex, race, education, diabetes, cardiovascular disease, hypertension, medications, and estimated glomerular filtration rate [eGFR]), but not with worse memory or working memory. Individuals with microalbuminuria or macroalbuminuria were more likely to be in the lower versus the highest tertile of executive functioning (odds ratio, 1.18; 95% confidence interval, 1.06 to 1.32; odds ratio, 1.19; 95% confidence interval, 1.05 to 1.35 per doubling of ACR in univariate and multivariable analyses, respectively). Albuminuria was associated with qualitative white matter hyperintensity grade (odds ratio, 1.13; 95% confidence interval, 1.02 to 1.25; odds ratio, 1.15; 95% confidence interval, 1.02 to 1.29 per doubling of ACR) in univariate and multivariable analyses and with quantitative white matter hyperintensity volume (beta = 0.11; P = 0.007; beta = 0.10; P = 0.01) in univariate and multivariable analyses of log-transformed data. Results were similar when excluding individuals with macroalbuminuria.LimitationsSingle measurement of ACR, indirect creatinine calibration, and reliance on participant recall for elements of medical history.ConclusionsAlbuminuria is associated with worse cognitive performance, particularly in executive functioning, as well as increased white matter hyperintensity volume. Albuminuria likely identifies greater brain microvascular disease burden.

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The relationship between white matter hyperintensities and cognitive reference abilities across the life span.

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The relationship between white matter hyperintensities and cognitive reference abilities across the life span.

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