Cognitive Problems a Family Affair for Parkinson's Patients

ROCHESTER, Minn., Oct. 9 -- Parkinson's disease, dementia, and cognitive decline may have strong family ties, reported U.S. and French investigators.

Relatives of patients with Parkinson's disease had a nearly 40% greater risk of cognitive decline or dementia compared with others in the general population, found a group led by Walter A. Rocca, M.D., M.P.H., at the Mayo Clinic here, and colleagues at the French National Institute of Health and Medical Research in Paris.

"This association is primarily driven by families of patients with younger age at onset of Parkinson's disease, but the risk does not vary across relatives of patients with different clinical characteristics of Parkinson's disease," the investigators wrote in the October issue of the Archives of Neurology. "The observed associations suggest the action of shared familial susceptibility factors, genetic or non-genetic."

There is conflicting evidence from clinical and epidemiologic studies of dementia risk among first-degree relatives of patients with Parkinson's disease, the authors noted.

"The co-occurrence of Alzheimer disease and Parkinson's disease in families and in individuals may be due to the sharing of susceptibility genetic variants (e.g., the apolipoprotein E gene)," the authors wrote. "In addition, Alzheimer disease brain lesions (plaques and tangles) and Parkinson's disease brain lesions (Lewy bodies) may share risk factors or could be reciprocally causal."

The authors conducted a historical cohort study of 1,019 first-degree relatives of 162 patients with Parkinson's disease and of 858 relatives of 147 matched controls chosen as a representative sample of the population of Olmsted County, Minn. They also evaluated 2,716 first-degree relatives of 411 patients with Parkinson's disease who were referred to the Mayo Clinic.

They called relatives of patients with Parkinson's disease and administered the Telephone Interview for Cognitive Status-Modified, a 12-item instrument. For relatives with dementia, proxies answered questions about the relative's memory and activities of daily living, and whether he or she had been diagnosed with Alzheimer's, dementia, or senility. The authors also extracted data on dementia from a medical-records linkage system.

The found that in the population-based sample, the risk of cognitive impairment or dementia among relatives of Parkinson's disease patients was significantly greater than that of relatives of controls (hazard ratio, 1.37, 95% confidence interval, 1.03-1.81; P=0.03).

In analyses adjusted for educational level and type of interview (proxy or interview or medical record only), the authors found that the younger the patient at age at the time of Parkinson's disease onset, the higher the risk for dementia or cognitive decline among his/her relatives.

In the overall population sample, the hazard ratio for dementia or cognitive decline among relatives of the youngest patients (66 or less at the age of Parkinson's onset) was 1.73 (95% CI 1.21 to 2.46, P=0.003).

"The findings were consistent in several sensitivity analyses," the authors noted. "In the referral-based sample, the risk of cognitive impairment or dementia in relatives increased with younger age at onset of Parkinson's disease but did not vary by other clinical characteristics."

The authors asserted that a strong point of the study was the use of separate assessments of the cognitive status of each relative in the study, rather than having a proband or single proxy provide family history.

They acknowledged as limitations their inability to eliminate certain biases from their sample. For example, first-degree relatives of Parkinson's disease patients participated at a higher rate and had more direct interviews than first-degree relatives of controls. They also noted that the proxy assessments of dementia or cognitive impairment were less than optimal methods for determining dementia, and that they were unable to determine the age of onset of cognitive impairment or dementia for some of the relatives.