To identify neuropsychiatric and somatic factors related to survival in early-onset Alzheimer's disease, we longitudinally studied 108 patients (35 male, 73 female) with early-onset Alzheimer's disease who were 46 to 64 years old at onset and 50 to 69 years old when diagnosed at our institution. A five-year follow-up, 30 patients had died. Pneumonia was the most common cause (73%), followed by malignancy (20%) and heart disease (7%). Kaplan-Meier survival curves showed a lower survival rate in patients with early-onset Alzheimer's disease than in age- and sex-matched life-table data in Japan. In Cox proportional hazards analysis, male gender, early disease onset, concurrent physical illness at time of diagnosis, and a low mini-mental state examination score increased the likelihood of death in patients with early-onset Alzheimer's disease. Our study confirmed that these patients have considerable excess mortality and a different pattern of cause of death than in the general population. Gender, age at onset, physical illness, and cognitive function strongly influenced survival. These factors may be predictors of mortality in patients with early-onset Alzheimer's disease that are useful in counseling patients and their families.

The purpose of the present study was to confirm an association of functional polymorphism within the serotonin transporter (5-HTT) gene with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) in mild AD. Apolipoprotein E (ApoE) gene polymorphism and 2 types of functional polymorphism in the 5-HTT gene, 5-HTTlinked polymorphic region (5-HTTLPR) and a 5-HTT variable number of tandem repeats sequence (5-HTTVNTR) were analyzed longitudinally in outpatients with mild AD to find out whether there was a relation between any such polymorphisms and the occurrence of BPSD. No significant differences in genotype distribution or allele frequencies were identified for 5-HTTLPR or 5-HTTVNTR between AD patients and age-and sex-matched non-demented controls regardless of ApoE ε4 allele. No significant differences were noted in 5-HTTLPR genotype or allele distributions between AD patients with or without BPSD. However, significant associations were observed between presence of 5-HTTVNTR allele 10 and BPSD or aggressiveness. This difference was independent of the presence of the ApoE ε4 allele. As a result, 5-HTT polymorphisms are unlikely to play any substantial role in susceptibility to AD. Conversely, 5-HTTVNTR influences the risk of developing BPSD or aggressiveness and genetic variations in the 5-HTT gene may be involved in the development of symptomatology for mild AD.

A 53-year-old woman who developed depression as the first symptom of multiple system atrophy was treated. Depression was followed successively by autonomic failure, parkinsonism and cerebellar ataxia. Treatment with l-DOPA, L-threo-DOPS, and thyroid releasing hormone was associated with improvement of autonomic failure and parkinsonism. As for depression, scores on the Zung scale and the Hamilton scale improved from 58 to 49 and from 30 to 22, respectively. This case is remarkable in that depression preceded neurologic dysfunction and was managed successfully by antiparkinsonian medication. A common underlying disturbance may be responsible for the depression and neurologic dysfunction in multiple system atrophy.

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Dopamine D3 receptor (DRD3) is present in the limbic system, which is thought to regulate affect, cognition, and activity. Thus a functional change in the DRD3 gene could in turn affect the cognitive and psychiatric symptoms of dementia of Alzheimer's type (DAT). We investigated a possible association of DRD3 genotype with DAT and the behavioral and psychological symptoms of dementia (BPSD) in mild DAT. The genotyping for DRD3 and apolipoprotein E (ApoE) was determined using restriction fragment length polymorphism in 210 patients with mild DAT and 224 age- and sex-matched non-demented controls. The occurrence of BPSD during the course of mild dementia was demonstrated using the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). No significant differences in DRD3 genotype were identified between DAT and controls, regardless of ApoE epsilon4. Among the DAT with BPSD, however, a significant association was observed between the presence of the DRD3 glycine allele and paranoid and delusional ideation, regardless of ApoE epsilon4. In conclusion, DRD3 gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of paranoid and delusional ideation during the course of mild DAT.