Background Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric... Show moreBackground Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design. Methods A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months. Results In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline. Conclusions Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline. 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
This thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2,... Show moreThis thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2, clinically relevant subtypes of apathy according to the Apathy Scale in older persons from the PROMODE study are examined, using data-driven Latent Class Analysis (LCA). Further, specific characteristics across the classes identified by LCA are investigated. Then, in Chapter 3, cross-sectionally the prevalence, severity and clinical profile of apathy in depressed and non-depressed older persons, in relation to various possible determinants is described. Chapter 4 examines which characteristics predict, over a 2-year period, the incidence and course of apathy in at baseline depressed older persons from the NESDO study. Chapter 5, using data of the NESDO and NESDA, investigates the presence of apathy in late-life compared to early-life depression, and various determinants of clinically relevant apathy in older compared to younger depressed persons. In Chapter 6 the association of the presence of apathy among community-dwelling older persons from the PROMODE study and a diminished quality of life is examined. All results are placed a current perspective in Chapter 7 that also discusses clinical implications, and makes some recommendations for future research. Show less
The overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP... Show moreThe overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP increases risk for cognitive decline in older persons. Older persons are at risk for impaired cerebral autoregulation, and lowering their BP may compromise cerebral blood flow and cognitive function. Contradictory to our hypothesis, the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden, a community-based randomized clinical trial in older persons (aged ≥75 years) with mild cognitive deficits, did not show that discontinuation of antihypertensive treatment improves cognitive functioning. The lack of the effect of this trial may be due to the unintentional inclusion of persons with a relatively intact cerebral autoregulation. Furthermore, we demonstrated that older persons with mild cognitive deficits and with orthostatic hypotension, who discontinued all their antihypertensive medication had an increased probability of being free from orthostatic hypotension 4 months later, compared to persons who continued their medication. Finally, in the DANTE MRI sub study, the relationship between BP and both conventional features of small vessel disease (SVD) and microstructural damage was explored, as well as the relation between microstructural damage and cognitive and psychological dysfunction. Show less
This thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic),... Show moreThis thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic), and a control group of non-carriers that had an a-priori 50% risk for HD. The study started in may 2004 and a second measurement was performed 2 years later. The aim of this study was to study the presence and course of both formal psychiatric disorders and neuropsychiatric symptoms, and to find correlates and predictors associated with the psychiatric phenomena. This cohort study confirms that neuropsychiatric symptoms frequently occur in patients with HD. We expected a diminished insight in patients with a neuropsychiatric symptoms like irritability, but most patients were aware of their irritability. A strong relationship was found between the presence of psychopathology, cognitive functioning and global daily functioning. Irritability may be an early sign of the disease, but only apathy was closely related to the progression of HD indicating a relationship with the progressive neurodegenerative nature of the disease. However, we also found associations with apathy and irritability, and the use of psychotropic medications. Show less
Groeneweg-Koolhoven, I.; Comijs, H.C.; Naarding, P.; Waal, M.W.M. de; Mast, R.C. van der 2015
