Markers of Prognosis in Neurodegenerative Dementia
Background: A prognostic marker should provide information about course and outcome of disease, e.g. predict time to a given endpoint or rate of progression due to disease in patients or subgroups of patients. Prognostic markers could be targeted to apply during the entire clinical course or just during distinct stages of the disease. Aim: The aim of this thesis is to identify, review and qualify possible indicators, including biological markers to predict course and time of survival in the two most common types of neurodegenerative dementia; AD and DLB/PDD. Study populations: I. 142 patients with AD. II. 79 patients with AD and 49 patients with DLB. III. 30 patients with DLB/PDD. IV. 32 patients with DLB PDD. Results: I. Patients with very high T-tau levels performed worse on cognitive tests at baseline, and exhibited a more rapid cognitive decline during follow up. Very high T-tau levels were also associated with a deviating cognitive profile characterized by symptoms from the medial temporal lobes. II. Patients with DLB had shorter length-of-survival compared to patients with AD, from the time of diagnosis, from the time of MMSE 20±1 and from the time of MMSE 17±1. III. Patients with persistent orthostatic hypotension exhibited shorter length-of-survival compared to patients with no or mild orthostatic hypotension. Patients with constipation and / or urinary incontinence, in addition to persistent orthostatic hypotension, had the shortest survival. IV. Patients, who received memantine instead of placebo during the first 6 months of follow-up, had a longer length-of survival. Patients, who responded positively to memantine lived longer compared to the non-responders. Conclusions: This thesis adds to current knowledge by reporting on studies on potential biomarkers that predict more rapid deterioration or shorter length-of-survival in neurodegenerative dementia. However, our findings must be confirmed in future research with larger study samples.
Clinical Medicine, Neurology, Lewy body disease, Alzheimer's disease, dementia with Lewy bodies, prognosis, survival, longitudinal studies, biomarkers, cerebrospinal fluid, dysautonomic orthostatic hypotension, memantine
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Clinical Memory Research Unit, Lund University