ABSTRACT
The clinical diagnosis in patients with parkinsonian disorders can be challenging, and a definite diagnosis requires neuropathological confirmation. The aim of this study was to examine whether a clinical diagnosis of Parkinson's disease (PD) and atypical parkinsonian disorders predict the presence of Lewy pathology (LP) and concomitant neuropathological lesions.We included 293 donors with a history of parkinsonism without dementia at disease onset, collected by the Netherlands Brain Bank (NBB) from 1989 to 2015. We retrospectively categorized donors according the International Parkinson and Movement Disorder Society clinical diagnostic criteria for PD (MDS-PD criteria) as 'not PD', 'probable PD' or 'established PD'. We compared the final clinical diagnosis to presence of neuropathological lesions as defined by BrainNet Europe and National Institute on Aging - Alzheimer's Association guidelines.LP was present in 150 out of 176 donors (85%) with a clinical diagnosis of PD, in 8 out of 101 donors (8%) with atypical parkinsonian disorders and in 4 out of 16 donors (25%) without a definite clinical diagnosis. Independent from age at death, stages of amyloid-ß, but not neurofibrillary tau or neuritic plaques, were higher in donors with LP compared to other types of pathology (p = 0.009). The MDS-PD criteria at a certainty level of 'probable PD' predicted presence of LP with a diagnostic accuracy of 89.3%. Among donors with LP, 'established PD' donors showed similar Braak α-synuclein stages and stages of amyloid-ß, neurofibrillary tau and neuritic plaques compared to 'not PD' or 'probable PD' donors.In conclusion, both a clinical diagnosis of PD as well as MDS-PD criteria accurately predicted presence of LP in NBB donors. LP was associated with more widespread amyloid-ß pathology, suggesting a link between amyloid-ß accumulation and LP formation.
Subject(s)
Brain/pathology , Lewy Bodies/pathology , Lewy Body Disease/pathology , Parkinson Disease/pathology , Adult , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Amyloid beta-Peptides , Amyotrophic Lateral Sclerosis/pathology , Autopsy , Female , Frontotemporal Dementia/pathology , Hallucinations/physiopathology , Humans , Lewy Body Disease/diagnosis , Lewy Body Disease/physiopathology , Male , Middle Aged , Multiple System Atrophy/diagnosis , Multiple System Atrophy/pathology , Multiple System Atrophy/physiopathology , Netherlands , Neurofibrillary Tangles/pathology , Parkinson Disease/diagnosis , Parkinson Disease/physiopathology , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/diagnosis , Parkinsonian Disorders/pathology , Parkinsonian Disorders/physiopathology , Plaque, Amyloid/pathology , Supranuclear Palsy, Progressive/diagnosis , Supranuclear Palsy, Progressive/pathology , Supranuclear Palsy, Progressive/physiopathologyABSTRACT
BACKGROUND: Visual hallucinations (VH) in Parkinson's disease (PD) are associated with PD dementia and have been related to cognitive impairments in non-demented PD patients. Reports on the specific cognitive domains affected are conflicting. The aim of the present study was to investigate the presence of specific cognitive impairments in non-demented PD patients with VH, compared to those without VH. METHODS: We compared the clinical characteristics and neuropsychological test scores of 31 non-demented PD patients with VH with those of 31 PD patients without VH that were carefully matched for sex, age, disease duration and educational level. Several non-motor symptoms, including depression, anxiety and sleep disturbances, were also taken into account, as these may influence cognitive performance. RESULTS: The PD with VH group performed significantly worse on the Trail Making Test part A (p = 0.01) and the Rey Auditory Verbal Learning Test, immediate recall (p = 0.01). In addition, PD patients with VH were more anxious, more depressed and reported more sleep disturbances. Verbal learning scores were not associated with levels of anxiety, depression or sleep disruption, whereas worse Trail Making Test A performance was associated with concomitant sleep disturbances. CONCLUSIONS: In non-demented PD patients, the presence of VH is associated with a cognitive profile characterized by impairments in verbal learning and probably attention. Since these cognitive functions are believed to be non-dopaminergic mediated functions, the present results support the hypothesis that multiple neurotransmitter systems, other than dopamine, contribute to the pathophysiology of VH in PD.
