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Familial Dementia With Lewy Bodies
A Clinical and Neuropathological Study of 2 Families
Debby W. Tsuang, MD, MSc;
Aaron M. Dalan, BS;
Charisma J. Eugenio, BS;
Parvonah Poorkaj, PhD;
Pornprot Limprasert, MD, PhD;
Albert R. La Spada, MD, PhD;
Ellen J. Steinbart, RN, MA;
Thomas D. Bird, MD;
James B. Leverenz, MD
Arch Neurol. 2002;59:1622-1630.
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  -synuclein immunostaining for Lewy body detection.
We conducted apolipoprotein E genotyping and sequenced the -, ß-,  -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)  4 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.
From the Department of Veterans Affairs Northwest Network Mental Illness
Research, Education, and Clinical Center (Drs Tsuang and Leverenz and Ms Eugenio)
and the Geriatric Research, Education, and Clinical Center, VA Puget Sound
Health Care System (Drs Poorkaj and Bird and Ms Steinbart); the Departments
of Psychiatry and Behavioral Sciences (Drs Tsuang and Leverenz), Neurology
(Drs La Spada, Bird, and Leverenz and Ms Steinbart), Laboratory Medicine (Drs
Limprasert and La Spada), and Internal Medicine (Drs Poorkaj and La Spada),
and the School of Medicine (Mr Dalan), University of Washington; and the Parkinson's
Disease Research, Education, and Clinical Center (Dr Leverenz), Seattle, Wash.
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