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White matter hyperintensities across the adult lifespan: relation to age, A? load, and cognition.

ABSTRACT: BACKGROUND:White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical ?-amyloid (A?) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. METHODS:One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical A?. The relationships of total and regional WMH to age, vascular risk factors, cortical A?, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (? or >?60?years old). RESULTS:WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater A?, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical A? load in the models did not alter the results, and there was no interaction between WMH and A? on cognition. CONCLUSION:WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. A? load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH.

SUBMITTER: Garnier-Crussard A

PROVIDER: S-EPMC7545576 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition.

Garnier-Crussard Antoine A Bougacha Salma S Wirth Miranka M André Claire C Delarue Marion M Landeau Brigitte B Mézenge Florence F Kuhn Elizabeth E Gonneaud Julie J Chocat Anne A Quillard Anne A Ferrand-Devouge Eglantine E de La Sayette Vincent V Vivien Denis D Krolak-Salmon Pierre P Chételat Gaël G

Alzheimer's research & therapy 20201008 1

<h4>Background</h4>White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults.<h4>Methods</h4>One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwe ...[more]

PMID: 33032654

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Project description:ObjectivesTo study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.DesignOngoing longitudinal study.SettingIn Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.ParticipantsIndividuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment).MeasurementsCognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education.ResultsMean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline.ConclusionWe show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019.

Project description:BackgroundPatients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small-vessel disease, measured by T2-weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline.ObjectiveTo investigate whether baseline orthostatic hypotension and autonomic dysfunction in early-stage PD affect later cognitive decline via mediation through cerebral small-vessel disease.MethodsDe novo PD patients (N = 365) and age-matched controls (N = 174) with baseline T2-weighted/ fluid-attenuated inversion recovery scans were selected from the Parkinson's Progression Markers Initiative. WMHs were automatically segmented. Mediation analysis was used to assess whether WMH load mediates the effect of orthostatic hypotension and autonomic dysfunction (measured by Scales for Outcomes in Parkinson's Disease-Autonomic) on future cognitive decline (measured by Montreal Cognitive Assessment) in an average of 4 years of follow-up.ResultsMediation analysis supported the existence of a full mediation of WMHs on the effect of diastolic orthostatic hypotension in patients with PD and future cognitive decline (average causal mediation effect: ab = -0.032, 95% confidence interval = -0.064 to -0.01, P = 0.01). There was also a partial mediation for overall autonomic dysfunction (ab = -0.027, 95% confidence interval = -0.054 to 0.00, P = 0.02).ConclusionsWMHs fully mediate the effect of diastolic orthostatic hypotension and partially mediate the effect of autonomic dysregulation on future cognitive decline in patients with PD. Our findings support the hypothesis that autonomic dysfunction in early clinical stages predisposes the brain to WMHs through dysregulation of the blood flow in the small vessels. This in turn increases the risk of future cognitive impairment in early PD.

Dataset Information

White matter hyperintensities across the adult lifespan: relation to age, A? load, and cognition.

Publications

White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition.

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