Er angst, apati og kognitiv sviktprofil assosiert med sykdomsprogresjon ved mild demens? Med hovedfokus på demens med Lewylegemer

Abstract

Background Dementia is a major public health problem in all parts of the world, and due to an aging population, the prevalence of dementia is growing. Two of the most frequent forms of dementias are Alzheimer`s disease (AD) and dementia with Lewy bodies (DLB). The vast majority of research is done on AD, and there is a lack of knowledge regarding DLB. Almost every person with dementia will experience behavioral and psychological symptoms (BPSD) in the course of the disease, and more knowledge is needed about the prognosis and associations with cognitive decline. Objectives We investigated whether anxiety, apathy and cognitive profiles were associated with dementia progression over four years in a cohort of patients with AD and DLB. In paper I we examined the associations between anxiety and dementia progression over four years in AD and DLB. In paper II we explored the differences between AD and DLB in performance changes on neuropsychological tests over four years. We also investigated whether cognitive domain scores at baseline could predict a negative outcome, such as faster disease progression or death. Finally we studied the associations of high and low visuospatial function at baseline and dementia progression. In paper III we investigated whether apathy was associated with the degree of cognitive impairment at baseline and cognitive decline over four years. In addition we explored if apathy was associated with time to nursing home admission and survival. Methods DemVest is a longitudinal study where patients with dementia and their caregivers have been recruited from clinics of old age psychiatry and geriatrics in the Western part of Norway. The inclusion criterion was mild dementia with Mini-Mental State Examination (MMSE) !20 or Clinical Dementia Rating (CDR) = 1. Patients with acute delirium, confusion, serious or terminal illness, previous or acute bipolar disorder or psychotic disorders were excluded. Dementia diagnoses were made in accordance with established criteria and pathologically confirmed in a subsample. Dementia severity rated with CDR and MMSE was used for cognitive screening. BPSD symptoms like anxiety, depression and apathy were rated with the Neuropsychiatric Inventory (NPI) and the Montgomery and Aasberg Depression Rating Scale (MADRS). A battery of neuropsychological tests was used for measuring cognition: Stroop test, Controlled Oral Word Associations Test, semantic fluency (COWAT), Boston Naming Test 15 items (BNT), Trail Making Test A and B (TMT A, TMT B), the California Verbal Learning Test-II (CVLT-II), Silhouettes and Cubes on the Visual Object and Space Perception Battery (VOSP). Longitudinal analyses were conducted with linear mixed effects models (LME), generalized linear mixed models (GLMM) and Kaplan-Meier and Cox regression. Results A total of 266 patients were included in the DemVest Study, and of these 128 were ultimately diagnosed with AD and 83 with DLB. Numbers of patients vary in the three papers due to continuous update of the dataset, and different inclusion criteria. Paper I: In most analyses, anxiety was not associated with changes in severity of cognitive impairment or dementia over four years. The only exception was for selfreported anxiety, which was associated with slower cognitive decline in patients with DLB compared to patients with AD. This should be cautiously interpreted due to uncertainties regarding the measure used and the patients degree of insight. The level of anxiety was higher in DLB than in AD at baseline and declined over four years, as opposed to AD where anxiety gradually increased. Paper II: There were no differences between AD and DLB in the rate of decline in any specific neuropsychological test over four years, except for in TMT A, but this should be cautiously interpreted due to missing data and the risk of familywise statistical error. High executive function at baseline was associated with a longer time to reach a negative outcome like severe dementia or death, but there were no differences between the diagnostic groups. There were no differences in visuospatial function or memory over time in the total sample, or between AD and DLB. There were no differences in rate of decline over time between patients with high or low visuospatial function at baseline. Paper III: In patients with DLB, apathy was associated with faster cognitive decline in MMSE over four years. Patients with DLB and apathy had shorter time until nursing home admission than DLB patients without apathy and patients with AD, regardless of apathy. At baseline, patients with apathy had decreased performance on Stroop Color and a composite executive function measure. Neurocognition was unaffected by apathy in the AD group, but in the DLB group patients with apathy had more verbal learning difficulties. Conclusions Anxiety does not seem to have an impact on the rate of dementia severity progression, but the level of anxiety decreased over four years in DLB and increased in AD. Executive function at baseline was associated with a slower progression for the total sample, but there were no differences between AD and DLB. Apathy seems to be associated with a faster cognitive decline and shorter time until nursing home admission for patients with DLB.