[Braak's hypothesis and non-motor symptoms of Parkinson disease]

In this review, we discuss dementia, depression, olfactory disturbance, sleep disorders and autonomic dysfunction as nonmotor symptoms of Parkinson disease (PD). PD with dementia (PDD) is defined as onset of dementia more than 1 year after the onset of parkinsonism. If dementia precedes or occurs less than 1 year after the onset of parkinsonism, a diagnosis of dementia with Lewy bodies (DLB) is made. There is essentially no difference in the pathology of PDD and DLB at autopsy, indicating that Braak's hypothesis, which is extracted from PD/PDD and excluding DLB, may be bias. REM-related behavioral disorder (RBD) or depression, the main locus of which is the brain stem, could precede or occur after the onset of PD or DLB, indicating a descending and ascending path of Lewy body (LB) pathology. A disturbance in olfaction usually precedes the onset of PD. Recent data indicate that severe olfactory dysfunction in PD is an indication of a high probability of mental decline. These clinical observations and our pathological reports support the presence of an olfactory-amygdala extension path of LB pathology in addition to Braak's hypothesis. Our pathological studies of consecutive autopsy cases showed that the involvement of autonomic ganglia was more frequent than that of the gastrointestinal tract, suggesting that initial the stage of LB pathology in Braak's hypothesis should be modified.