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White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia.

ABSTRACT: To explore the relationship between white matter hyperintensities (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer's disease (AD) and Lewy body dementia.This is a prospective cohort study conducted in secondary care outpatient clinics in western Norway.The study population consisted of 77 elderly people with mild dementia diagnosed according to standardised criteria.Structured clinical interviews and physical, neurological, psychiatric, and neuropsychological examinations were performed and routine blood tests were taken. Depression was assessed using the depression subitem of the Neuropsychiatric Inventory and the Montgomery-Åsberg Depression Rating Scale (MADRS). A standardised protocol for magnetic resonance imaging scan was used, and the volumes of WMH were quantified using an automated method, followed by manual editing.The volumes of total and frontal deep WMH were significantly and positively correlated with baseline severity of depressive symptoms, and depressed patients had significantly higher volumes of total and frontal deep WMH than non-depressed patients. Higher volumes of WMH were also associated with having a high MADRS score and incident and persistent depression at follow-up. After adjustment for potential confounders, frontal deep WMH, in addition to prior depression and non-AD dementia, were still significantly associated with baseline depressive symptoms (p = 0.015, OR 3.703, 95% CI 1.294-10.593). Similar results emerged for total WMH.In elderly people with mild dementia, volumes of WMH, in particular frontal deep WMH, were positively correlated with baseline severity of depressive symptoms, and seemed to be associated with persistent and incident depression at follow-up. Further studies of the mechanisms that determine the course of depression in mild dementia are needed.

SUBMITTER: Soennesyn H

PROVIDER: S-EPMC3347877 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other

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White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia.

Soennesyn Hogne H Oppedal Ketil K Greve Ole Jacob OJ Fritze Friederike F Auestad Bjørn H BH Nore Sabine P SP Beyer Mona K MK Aarsland Dag D

Dementia and geriatric cognitive disorders extra 20120101

<h4>Objectives</h4>To explore the relationship between white matter hyperintensities (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer's disease (AD) and Lewy body dementia.<h4>Design</h4>This is a prospective cohort study conducted in secondary care outpatient clinics in western Norway.<h4>Subjects</h4>The study population consisted of 77 elderly people with mild dementia diagnosed according to standardised criteria.<h4>Methods</h4>Structured clinical interviews and p ...[more]

PMID: 22590471

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Project description:Background and objectivesThe menopause transition is increasingly recognized as a time of importance for women's brain health. A growing body of work indicates that the classic menopausal symptom, vasomotor symptom (VMS), may be associated with poorer cardiovascular health. Other work links VMS to poorer cognition. We investigate whether VMS, when rigorously assessed using physiologic measures, are associated with greater white matter hyperintensity volume (WMHV) among midlife women. We consider a range of potential explanatory factors in these associations and explore whether VMS are associated with the spatial distribution of WMHV.MethodsWomen aged 45-67 years and free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were considered in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, and occipital) and additional covariates including sleep.ResultsThe study sample included 226 women. Physiologically assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest associations observed for sleep VMS (24-hour VMS, B[SE] = 0.095 [0.045], p = 0.032; Wake VMS, B[SE] = 0.078 [0.046], p = 0.089, Sleep VMS, B[SE] = 0.173 [0.060], p = 0.004). Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep WMHV, periventricular WMHV, and frontal lobe WMHV.DiscussionVMS, particularly VMS occurring during sleep, were associated with greater WMHV. Identification of female-specific midlife markers of poor brain health later in life is critical to identify women who warrant early intervention and prevention. VMS have the potential to serve as female-specific midlife markers of brain health in women.

Project description:Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD. The aim of the current study was to investigate the longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers. 336 participants in the Genetic FTD Initiative (GENFI) study were included in the analysis: 101 presymptomatic and 32 symptomatic GRN mutation carriers, as well as 203 mutation-negative controls. 39 presymptomatic and 12 symptomatic carriers, and 73 controls also had longitudinal data available. Participants underwent MR imaging acquisition including isotropic 1 mm T1-weighted and T2-weighted sequences. WMH were automatically segmented and locally subdivided to enable a more detailed representation of the pathology distribution. Log-transformed WMH volumes were investigated in terms of their global and regional associations with imaging measures (grey matter volumes), biomarker concentrations (plasma neurofilament light chain, NfL, and glial fibrillary acidic protein, GFAP), genetic status (TMEM106B risk genotype) and cognition (tests of executive function). Analyses revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time. In particular, lesions were seen periventricularly in frontal and occipital lobes, progressing to medial layers over time. However, there was variability in the WMH load across GRN mutation carriers - in the symptomatic group 25.0% had none/mild load, 37.5% had medium and 37.5% had a severe load - a difference not fully explained by disease duration. GM atrophy was strongly associated with WMH load both globally and in separate lobes, and increased WMH burden in the frontal, periventricular and medial regions was associated with worse executive function. Furthermore, plasma NfL and to a lesser extent GFAP concentrations were seen to be associated with increased lesion burden. Lastly, the presence of the homozygous TMEM106B rs1990622 TT risk genotypic status was associated with an increased accrual of WMH per year. In summary, WMH occur in GRN mutation carriers and accumulate over time, but are variable in their severity. They are associated with increased GM atrophy and executive dysfunction. Furthermore, their presence is associated with markers of WM damage (NfL) and astrocytosis (GFAP), whilst their accrual is modified by TMEM106B genetic status. WMH load may represent a target marker for trials of disease modifying therapies in individual patients but the variability across the GRN population would prevent use of such markers as a global outcome measure across all participants in a trial.

Project description:ImportanceAlthough white matter hyperintensities (WMHs) are associated with the risk for Alzheimer disease, it is unknown whether they represent an independent source of impairment or interact with known markers of disease.ObjectiveTo examine the degree to which WMHs predict aggressive cognitive decline among individuals with mild cognitive impairment, either independently or by modifying the effects of entorhinal cortex volume (ECV), a marker of Alzheimer disease-related neurodegeneration.Design, setting, and participantsThe Alzheimer's Disease Neuroimaging Initiative is a longitudinal study with 6-month follow-up visits. Three hundred thirty-two participants (mean [SD] age, 74.6 [7.4] years; 118 women) of a total of 374 participants diagnosed as having mild cognitive impairment were included. Participants were excluded if they did not have longitudinal data, apolipoprotein E genotype data, or had evidence of supratentorial infarct.Main outcomes and measuresA decline in Mini-Mental State Examination score of 3 points over 6 months or 6 points over 1 year between consecutive visits was defined as aggressive decline. White matter hyperintensity volume and ECV were entered as predictors in Cox proportional hazards models and Wilcoxon-Breslow tests to examine their impact on this outcome, adjusting for sex, age, education, and apolipoprotein E status.ResultsGreater WMH volume at baseline, apolipoprotein E ε4 status, and smaller ECV at baseline were associated with an increased risk for aggressive decline (hazard ratio [HR], 1.23; 95% CI, 1.05-1.43; P = .01 for WMH volume; HR, 1.49; 95% CI, 1.09-2.05; P = .04 for apolipoprotein E ε4 status; HR, 0.66; 95% CI, 0.55-0.79; P < .001 for ECV). White matter hyperintensity volume modified the effect of ECV on aggressive decline risk: individuals with high ECV and low WMH were at particularly low likelihood of decline (χ2 = 15, P = .001). Participants with Mini-Mental State Examination scores that declined by 3 or more points over 6 months or 6 or more points over 12 months were more likely to have converted to Alzheimer disease by the end of the follow-up period (χ2 = 82, P < .001).Conclusions and relevanceWhite matter hyperintensity burden and ECV predict rapid cognitive decline among individuals with mild cognitive impairment both additively and multiplicatively.

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White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia.

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White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia.

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