Regular Research Article
Familial Occurrence of Dementia With Lewy Bodies

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Objective

The authors investigated the validity of the designation “familial dementia with Lewy bodies (DLB)” by evaluating the clinical, neuropathological, and genetic characteristics of previously reported families exhibiting both familial parkinsonism and dementia.

Methods

Several families, including multiple individuals with parkinsonism as well as prominent dementia, were identified through a literature search. Selected families had at least one member with dementia with autopsy evidence of neocortical and/or limbic Lewy-body (LB) pathology. Clinical and neuropathological evidence from reports of families with prominent dementia as well as parkinsonism was reviewed to further define familial DLB.

Results

All selected families had at least one affected individual with dementia and autopsy-proven DLB. Therefore, these families might be considered examples of familial DLB. Individuals in the first six families typically presented with parkinsonian features, whereas cognitive decline did not appear until years later. In contrast, in the other six families, affected individuals typically presented with cognitive decline, and parkinsonism developed later.

Conclusions

Families exist in which one or more persons meet both clinical and neuropathological criteria for DLB. They differ as to whether the signs of parkinsonism precede or follow signs of dementia. It remains to be determined whether this clinical distinction is biologically important. Susceptibility to developing LB pathology may be determined by the interaction between genetic predisposition and environmental risk factors.

Section snippets

METHODS

To find studies on kindreds with DLB, we used the PubMed database (www.ncbi.nlm.nih.gov). We identified approximately 570 indexed articles addressing familial parkinsonism. As expected, when we reviewed the selected articles, the majority of affected members in these families had predominant parkinsonism.12, 14, 15 If dementia was present in these families, it occurred in very few affected individuals.12 Furthermore, many of the studies included only autopsy-confirmed cases with

RESULTS

See Table 1 for composite information on families. Family data are presented in chronological order by publication date.

CONCLUSIONS

The present study describes the clinical, neuropathological, and genetic characteristics of 12 families exhibiting familial parkinsonism and dementia. All families had at least one affected individual with dementia and autopsy-proven DLB. Therefore, these families might be considered examples of familial DLB. Individuals in the first six families described here typically presented with parkinsonian features, with cognitive decline not appearing until years later. In contrast, in the other six

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