The Neuropathologic Substrate of Parkinson Disease Dementia

Abstract

Corresponding author Kurt A. Jellinger, MD Institute of Clinical Neurobiology, Kenyongasse 18, A-1070 Vienna, Austria Tel +43-1-5266534 Fax +43-1-5266534 E-mail kurt.jellinger@univie.ac.at Dementia has been increasingly recognized to be a common feature in patients with Parkinson disease (PD), especially in old age, referred to as Parkinson disease dementia (PDD), and in dementia with Lewy bodies (DLB), which are currently believed to represent two phenotypes in a disease spectrum, characterized pathologically by deposition of α-synuclein (αSyn) within nerve cells (Lewy bodies, LBs) and dystrophic (Lewy) neurites in the central and autonomic nervous system, and clinically by a variable mixture of cognitive, neuropsychiatric, extrapyramidal, and vegetative features. Clinical and pathological diagnostic criteria for PDD and DLB and interrater assessment of αSyn pathology have been published recently. Dementia in PD with incidence rates of 95-112.5/100 patient-years (odds ratio for dementia in PD of 3.5), a point prevalence close to 30% and a cumulative prevalence between 48 and 78% after 15 and 18 years follow-up, respectively, is suggested to have a 4 to 6 times increased lifetime incidence rate compared to age-matched controls. Prevalence estimates for DLB, depending on criteria, range from 0 to 5% of the general population and, in several autopsy series, from 0 to 30% (mean 15-20%) of all dementia cases, with an incidence of 0.1 per year for the general population and 3.2% per year for new dementia cases. A recent clinico-pathologic study confirmed essential clinical differences between PD with and without dementia and DLB: PDD patients were significantly older at death and had a shorter duration of illness and lower mini-mental status examination (MMSE) scores than non-demented PD cases.