Familial dementia with Lewy bodies - A clinical and neuropathological study of 2 families

Background: Dementia with Lewy bodies (DLB) is characterized by early dementia and associated visual hallucinations, parkinsonism, and fluctuations in cognition. Few families with DLB have been described with detailed clinical, pathological, and genetic assessments. Objective: To investigate the clinical, neuropathological, and genetic characteristics of families with 2 or more autopsy-proven cases of DLB. Design: Consecutive cases with the neuropathological diagnosis of DLB were reviewed as part of a case series. Families included in this study have 2 or more autopsy-proven cases of DLB available and a positive family history of dementia. We obtained clinical and neuropathological data on all first-degree relatives. Neuropathological evaluations included alpha-synuclein immunostaining for Lewy body detection. We conducted apolipoprotein E genotyping and sequenced the alpha-, beta-, gamma-synuclein, and parkin genes. Setting: Subjects were selected from the neuropathology core of the University of Washington's Alzheimer's Disease Research Center. Patients: The study investigated 2 families. Clinical information was obtained from 10 individuals in family 1 and 7 individuals in family 2. Neuropathological examinations were conducted in 3 individuals in family 1 and 2 individuals in family 2. Main Outcome Measures: Each subject was examined for the presence of clinical symptoms and neuropathological findings consistent with DLB. Results: While all affected individuals presented with dementia in both families, only individuals in family 1 developed visual hallucinations and delusions. Parkinsonism, if present, occurred later in the course of illness. Neuropathological examination revealed Lewy bodies in all patients, while 1 patient from each family also met the neuropathological criteria for Alzheimer disease. All affected individuals carried at least 1 APOE (apolipoprotein E) epsilon4 allele, while there were no nucleotide alterations in the synuclein or parkin genes. Conclusions: Familial DLB exists, although there is substantial clinical and neuropathological heterogeneity within and between families. Additional clinicopathologic and genetic studies are necessary to further our understanding of DLB.