Identifying cardiovascular mechanisms as determinants of neuropsychiatric symptoms in dementia

Neuropsychiatric symptoms, such as apathy, agitation and aggressive behaviour, are very common in people with all types of dementia. The frequency of neuropsychiatric symptoms is much higher in people with dementia than in the general population. Almost all people diagnosed with dementia develop neuropsychiatric symptoms at some stage during their disease with apathy as the most persistent and most frequent neuropsychiatric symptom. Neuropsychiatric symptoms severely affect quality of life and general daily functioning, hamper optimal care, are a burden for carers and are the main reason for institutionalisation. In contrast with their high clinical relevance and consequences, relatively little is known about the causes of neuropsychiatric symptoms. Hence this research project. The aetiology of neuropsychiatric symptoms in dementia is multifactorial and includes unmet physical and psychological needs related to dementia. Limited translational research into neuropsychiatric symptoms and biological factors suggests that genetics, medical comorbidities, lifestyle choices and neuropathological changes in the brain all may play a role in the development of neuropsychiatric symptoms. More specifically, there is increasing evidence from neuroimaging studies that hypoperfusion of the brain plays a role in the development of neuropsychiatric symptoms. Hypertension and cardiovascular disease can cause disturbances in cerebrovascular hemodynamics and hypoperfusion of (specific) brain areas. In addition, in people with dementia, the use of antihypertensive medication is associated with increased occurrence of neuropsychiatric symptoms. All suggesting a potential cardiovascular component in the development of neuropsychiatric symptoms. It is, however, underexposed in research and (therefore) may be very unknown to healthcare professionals treating people with dementia. Therefore, the first aim of this research project is to provide an overview of the current knowledge (scientific and of healthcare professionals) regarding the association between cardiovascular mechanisms and neuropsychiatric symptoms in dementia. To gain more insight on the existing scientific evidence on cardiovascular mechanisms, including hypotension as a biological factor, a systematic review will provide overview. Qualitative research will provide more insight in the beliefs, knowledge and perspectives of healthcare professionals on the development of neuropsychiatric symptoms. The second aim of this research proposal is to provide more evidence regarding the potential cardiovascular component, including blood pressure and the use of antihypertensive treatment, of neuropsychiatric symptoms in general and apathy in particular. Studies in nursing home residents with dementia can provide a valuable source of data on these associations since neuropsychiatric symptoms are prevalent in nursing home residents with dementia. The data from the Communication, Systematic pain treatment, Medication review, Organized activities and Safety (COSMOS) study will be used to assess the association between blood pressure, the use of antihypertensive medication and neuropsychiatric symptoms. Since apathy is the most persistent and most frequent neuropsychiatric symptom, this research project will study apathy more in depth. In the Discontinuation of ANtihypertensive Treatment in Older people with dementia living in a Nursing home (DANTON) study, there is an opportunity to include an extra apathy questionnaire, the abbreviated Apathy Evaluation Scale-10, at baseline and during follow-up. Within this study, we will assess the association between the change in blood pressure and the change in neuropsychiatric symptoms in general and apathy in particular. Where we will be able to compare the score on the apathy domain of the Neuropsychiatric Inventory – Nursing Home version with the abbreviated Apathy Evaluation Scale-10. To get more insight into hypoperfusion as possible determinant, neuroimaging studies are needed for cerebral blood flow measurements, most frequently using MRI techniques. MRI examinations are proven more difficult in people with advanced dementia. Transcranial doppler examinations might be a welcome alternative to assess (a proxy) of cerebral blood flow. However, this is not very often done. Therefore, the third aim of this research project is to perform a feasibility study to assess whether transcranial doppler examinations can be executed in nursing home residents with advanced dementia. With this project we will provide more insight in cardiovascular mechanisms as determinants of neuropsychiatric symptoms, with more depth analysis on apathy. In addition, the feasibility study will answer the question whether transcranial doppler examinations are feasible in a nursing home setting. This offers an opportunity for future research to develop (non)pharmacological treatment strategies aiming for better care and quality of life for people with dementia.