The morphological basis of mental dysfunction in Parkinson's disease

Mental dysfunction including dementia in Parkinson's disease (PD), the incidence of which averages 20–40%, is suggested to have six-fold lifetime risk compared to age-matched controls. It is caused by a variety of functional and pathological lesions ranging from damage to subcortical–cortical networks to cortical and limbic Lewy body and neuritic Alzheimer pathologies, the relationship and impact of which are still under discussion. Based on two consecutive autopsy series of PD, with prevalence of cognitive impairment of 33% to 35.7%, its essential morphological changes and their impact on the natural history (survival) are discussed. Whereas cortical Lewy body stages 5 and 6 without additional pathologies only rarely were associated with dementia, around 20% of demented PD cases were classified as dementia with Lewy bodies (DLB) with variable degrees of Alzheimer (AD) pathology, and around one third showed severe neuritic AD lesions which occurred in PD patients with later disease onset and significantly shorter survival. Frequent close relations in the severity between α-synuclein and tau-pathologies suggest synergistic reaction and common underlying pathogenesis of both lesions. Clinico-pathological studies in PD showed a significantly negative relation between cognitive impairment and neuritic AD lesions somewhat different from that in AD, suggesting that neuritic AD pathology, either alone or in combination with cortical and limbic Lewy bodies, are major causes of mental and cognitive dysfunction in PD.