Lewy body dementia (LBD) is a progressive brain disorder defined by abnormal protein deposits that disrupt normal brain function. These deposits, called Lewy bodies, lead to difficulties with thinking, movement, and mood. For families affected by this condition, a common question is whether the disease is passed down through generations. The answer is complex, involving an interplay of genetic predispositions and other factors.
The Role of Genetics in LBD
In most instances, Lewy body dementia is sporadic, meaning it occurs in individuals without any known family history of the disorder. These cases arise from a combination of factors, not a single inherited cause. This is different from strictly hereditary diseases, where a gene passed from a parent results in a high probability of the child developing the condition. Instead, some people have genetic risk factors that increase their susceptibility.
A small number of LBD cases are considered “familial,” where multiple family members are affected. Research has identified several genes that, when mutated, can increase the risk for LBD. Three of the most studied genes are SNCA, GBA, and APOE.
The SNCA gene provides instructions for making alpha-synuclein, the primary protein component of Lewy bodies. Mutations can cause this protein to misfold and clump together.
Variations in the GBA gene are also a risk factor. This gene is responsible for producing an enzyme that helps with the disposal of cellular waste. When the GBA gene is altered, this waste disposal system can become less efficient, which may contribute to the formation of Lewy bodies. The APOE gene, particularly the APOE e4 variant, is associated with an increased risk of developing LBD, similar to its role in Alzheimer’s disease.
Established Non-Genetic Risk Factors
Beyond genetics, several other factors are known to influence the likelihood of developing LBD. The primary non-genetic risk factor is advanced age. The disease begins at age 50 or older, and the risk increases as a person gets older. Data also suggests that males have a slightly higher incidence of LBD compared to females, though the reasons for this difference are not yet understood.
A strong association exists between a specific sleep disorder and the future development of LBD. This condition, known as REM sleep behavior disorder (RBD), causes individuals to physically act out their dreams with vocal sounds and sudden movements. The presence of RBD is an early indicator, as many individuals who have it later develop LBD or a related disorder like Parkinson’s disease. Environmental exposures may also play a role, although specific environmental triggers have not been definitively identified.
Understanding Genetic Testing for LBD
Genetic testing for LBD is not a standard part of the diagnostic process. While tests can identify risk-associated gene variants like those in GBA or APOE, the results do not provide a definitive prediction of the disease. A positive result for a risk variant means a person’s chances of developing LBD are higher than the general population’s, but it does not confirm they will get the disease.
Conversely, a negative result does not eliminate the possibility of developing LBD, as the majority of cases are not linked to these specific high-risk genes. For these reasons, anyone considering genetic testing should first seek genetic counseling. A counselor can help individuals understand the potential implications of test results for themselves and their family members and explain the difference between risk and certainty.
The Connection Between LBD, Parkinson’s, and Alzheimer’s Disease
Understanding LBD requires looking at its relationship with other neurodegenerative diseases, particularly Parkinson’s and Alzheimer’s. LBD and Parkinson’s disease are both classified as “synucleinopathies,” which are disorders characterized by the abnormal accumulation of the alpha-synuclein protein. This shared pathology explains why the two conditions have overlapping symptoms and share genetic risk factors like mutations in the SNCA and GBA genes.
The primary distinction between dementia with Lewy bodies and Parkinson’s disease dementia is the timing of symptoms. In dementia with Lewy bodies, cognitive problems appear within a year of the onset of movement problems. In Parkinson’s disease dementia, the motor symptoms are established for at least a year before significant cognitive decline begins.
The connection to Alzheimer’s disease is also important, primarily through the APOE gene. This genetic overlap can sometimes lead to a mixed pathology, where the brain shows the protein abnormalities of both diseases—the Lewy bodies of LBD and the amyloid plaques and tau tangles of Alzheimer’s. This helps explain why a family history of Parkinson’s or Alzheimer’s might be relevant to an individual’s LBD risk.