Dataset Information

Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.

ABSTRACT: Our objective was to investigate the association between hypertension and concurrent impairments in mobility, cognition, and mood; the role of brain white matter hyperintensities in mediating this association; and the impact of these impairments on disability and mortality in elderly hypertensive individuals.-Blood pressure, gait speed, digit symbol substitution test, and the Center for Epidemiological Studies Depression Scale were measured yearly (1992-1999) on 4700 participants in the Cardiovascular Health Study (age: 74.7, 58% women, 17% blacks, 68% hypertension, 3600 had brain magnetic resonance imaging in 1992-1993, survival data 1992-2005). Using latent profile analysis at baseline, we found that 498 (11%) subjects had concurrent impairments and 3086 (66%) were intact on all 3 measures. Between 1992 and 1999, 651 (21%) became impaired in all 3 domains. Hypertensive individuals were more likely to be impaired at baseline (odds ratio 1.23, 95% confidence interval 1.04 to 1.42, P=0.01) and become impaired during the follow-up (hazard ratio=1.3, 95% confidence interval 1.02 to 1.66, P=0.037). A greater degree of white matter hyperintensities was associated with impairments in the 3 domains (P=0.007) and mediated the association with hypertension (P=0.19 for hypertension after adjusting for white matter hyperintensities in the model, 21% hazard ratio change). Impairments in the 3 domains increased subsequent disability with hypertension (P<0.0001). Hypertension mortality also was increased in those impaired (compared with unimpaired hypertensive individuals: HR=1.10, 95% confidence interval 1.04 to 1.17, P=0.004).Hypertension increases the risk of concurrent impairments in mobility, cognition, and mood, which increases disability and mortality. This association is mediated in part by microvascular brain injury.

SUBMITTER: Hajjar I

PROVIDER: S-EPMC3081662 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.

Hajjar Ihab I Quach Lien L Yang Frances F Chaves Paulo H M PH Newman Anne B AB Mukamal Kenneth K Longstreth Will W Inzitari Marco M Lipsitz Lewis A LA

Circulation 20110214 8

<h4>Background</h4>Our objective was to investigate the association between hypertension and concurrent impairments in mobility, cognition, and mood; the role of brain white matter hyperintensities in mediating this association; and the impact of these impairments on disability and mortality in elderly hypertensive individuals.<h4>Methods and results</h4>-Blood pressure, gait speed, digit symbol substitution test, and the Center for Epidemiological Studies Depression Scale were measured yearly ( ...[more]

PMID: 21321150

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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.

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.

Dataset Information

Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.

Publications

Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.

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