Psychiatric symptoms as preceding or early signs of dementia of Alzheimer type. A cohort study.

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In total of 188 Alzheimer's disease (AD) patients (51 men and 137 women), who were admitted to Tokyo Metropolitan Matsuzawa Hospital, 13.1% of female patients and 2% of male patients had hallucination and/or delusion as early symptoms of the disease. The male patients also tended to have abnormal behavior or depression. Patients with AD type dementia, who show depression, hallucination or delusion as early symptoms, are often diagnosed neuropathologically as dementia with Lewy bodies (DLB). The vast majority of DLB patients had heavy accumulation of amyloid beta protein (Aβ) and neurofibrillary changes in the limbic cortices similarly to AD patients. On the other hand, those who do not fulfill the criteria for DLB and are, thus, diagnosed as AD, often have mild Lewy body pathology. It seems that the occurrence of psychiatric symptoms in dementia of AD type is related to the overlap between AD lesions and DLB lesions. However, thinking of these two diseases in a single entity or a group of diseases, a yet unsolved question is paucity of neurofibrillary changes in the neocortex of DLB, which seems to be unproportionate to the degree of Aβ deposits. In this study, we have demonstrated heavy accumulation of α-synuclein in the neuronal processes in the neocortex of DLB by immunohistochemistry of postmortem brain tissues from DLB patients using the antibodies to phosphorylated α-synuclein. Quantitative analyses have indicated that the amount of neuritic α-synuclein accumulation in DLB is comparable with that of neuritic tau accumulation in AD. The total of neuritic α-synuclein and tau accumulation is proportionate to the degree of Aβ deposits regardless of the cases is DLB or AD. Aβ may promote accumulation of not only tau but also α-synuclein. We speculate that, if the process is shifted toward tau accumulation, the manifestation becomes AD, and, if it is shifted toward α-synuclein accumulation, the manifestation becomes DLB