Ageing is associated with functional reorganization that is mainly characterized by declining functional connectivity due to general neurodegeneration and increasing incidence of disease.... Show moreAgeing is associated with functional reorganization that is mainly characterized by declining functional connectivity due to general neurodegeneration and increasing incidence of disease. Functional connectivity has been studied across the lifespan; however, there is a paucity of research within the older groups (>= 75 years) where neurodegeneration and disease prevalence are at its highest. In this cross-sectional study, we investigated associations between age and functional connectivity and the influence of cerebral small vessel disease (CSVD)-a common age-related morbidity-in 167 community-dwelling older adults aged 75-91 years (mean = 80.3 +/- 3.8). Resting-state functional MRI was used to determine functional connectivity within ten standard networks and calculate the whole brain graph theoretical measures global efficiency and clustering coefficient. CSVD features included white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy that were assessed in each individual and a composite score was calculated. Both main and interaction effects (age*CSVD features) on functional connectivity were studied. We found stable levels of functional connectivity across the age range. CSVD was not associated with functional connectivity measures. To conclude, our data show that the functional architecture of the brain is relatively unchanged after 75 years of age and not differentially affected by individual levels of vascular pathology. Show less
The aim of this thesis was to investigate cardiovascular determinants of neurocognitive functioning in old age, in particular cognitive dysfunction, depressive symptoms, and apathy. First, we found... Show moreThe aim of this thesis was to investigate cardiovascular determinants of neurocognitive functioning in old age, in particular cognitive dysfunction, depressive symptoms, and apathy. First, we found that the Geriatric Depression Scale(GDS)-3A, the apathy sub set of the GDS-15, moderately discriminates between presence and absence of apathy, and can be used in large study populations to investigate associations with apathy. Next, we demonstrated that higher levels of high sensitivity cardiac troponin T (hs-cTnT), a clinical cardiac biomarker, are related to accelerated cognitive decline, but not to apathy or depression.In the next chapters, we tested the hypothesis that in those older persons with more vascular brain damage, a lower rather than a higher blood pressure is related to worse neurocognitive function. Indeed, we found that only in those older persons with worse daily functioning and those with more cerebral small vessel disease, lower blood pressure was related to more symptoms of apathy. This pattern was not observed for depression or cognitive function.In conclusion, we found that cardiovascular risk factors are important for neurocognitive functioning in older persons. Moreover, we found that specific cardiovascular determinants, such as blood pressure and hs-cTnT, have different associations with apathy than with depression and cognitive function. Show less
Buhrmann, A.; Brands, A.M.A.; Grond, J. van der; Schilder, C.; Mast, R.C. van der; Ottenheim, N.R.; ... ; Berg, E. van den 2020
The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter... Show moreThe cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning. Show less
Bertens, A.S.; Foster-Dingley, J.C.; Grond, J. van der; Moonen, J.E.F.; Mast, R.C. van der; Ottenheim, N.R. 2020
BACKGROUND In older persons, both high and low blood pressure (BP) levels are associated with symptoms of apathy. Population characteristics, such as burden of cerebral small-vessel disease (CSVD),... Show moreBACKGROUND In older persons, both high and low blood pressure (BP) levels are associated with symptoms of apathy. Population characteristics, such as burden of cerebral small-vessel disease (CSVD), may underlie these apparently contradictory findings. We aimed to explore, in older persons, whether the burden of CSVD affects the association between BP and apathy.DESIGN Cross-sectional study.SETTING Primary care setting, the Netherlands.PARTICIPANTS Community-dwelling older persons (mean age = 80.7 years; SD = 4.1 years) with mild cognitive deficits and using antihypertensive treatment, participating in the baseline measurement of the magnetic resonance imaging substudy (n = 210) of the Discontinuation of Antihypertensive Treatment in the Elderly Study Leiden.MEASUREMENTS During home visits, BP was measured in a standardized way and apathy was assessed with the Apathy Scale (range = 0-42). Stratified linear regression analyses were performed according to the burden of CSVD. A higher burden of CSVD was defined as 2 or more points on a compound CSVD score (range = 0-3 points), defined as presence of white matter hyperintensities (greater than median), any lacunar infarct, and/or two or more microbleeds.RESULTS In the entire population, those with a lower systolic and those with a lower diastolic BP had more symptoms of apathy (beta = -.35 [P = .01] and beta = -.66 [P = .02], respectively). In older persons with a higher burden of CSVD (n = 50 [24%]), both lower systolic BP (beta = -.64, P = .02) and lower diastolic BP (beta = -1.6, P = .01) were associated with more symptoms of apathy, whereas no significant association was found between BP and symptoms of apathy in older persons with a lower burden of CSVD (n = 160).CONCLUSIONS Particularly in older persons with a higher burden of CSVD, lower BP was associated with more symptoms of apathy. Adequate BP levels for optimal psychological functioning may vary across older populations with a different burden of CSVD. Show less
ObjectiveHigh blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our... Show moreObjectiveHigh blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.MethodsTo identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.ResultsOver 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those <= 65 years of age.ConclusionOur findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.Clinical trials registrationThe review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454. Show less
