SALT LAKE CITY — A number of novel risk factors—many sharing the common denominator of cholinergic dysfunction—emerged as potential early markers of dementia in Parkinson's disease in a longitudinal study of newly diagnosed patients.
Gastrointestinal, urologic, and cardiac disorders emerged as predictors in the massive DATATOP study, a project of the Parkinson Study Group. The study enrolled and extensively studied 740 newly diagnosed, untreated Parkinson's disease (PD) patients for more than 5 years.
The primary objective of the study was to compare deprenyl with tocopherol in the treatment of early PD, with deprenyl showing short-term benefit (Ann. Neurol. 1998;44:[S]160–6).
However, the large database also permitted examination of other questions, such as the progressive emergence of dementia in a relatively young, early-stage population. The mean age of DATATOP participants at enrollment was 61, and their Hoehn-Yahr Parkinson's disease stage averaged 1–2.5 on the 5-stage scale.
Dr. Ergun Y. Uc of the University of Iowa, Iowa City, reported the results in an oral presentation at the annual meeting of the American Neurological Association.
Dementia symptoms developed in 2.4% of 740 subjects in the first 2 years of follow-up and in 5.8% of subjects in the first 5 years, an incidence rate higher than that seen in the general population, but lower than what is usually seen in Parkinson's populations.
The annual incidence rate for dementia development in the group was 12.7 per 1,000. Baseline predictors of dementia included well-known risk factors such as older age, male gender, and Postural Instability and Gait Disorder (PIGD) score, as well as the predictable signal of lower scores on cognitive psychological tests at enrollment.
Several additional risk factors emerged as well, including gastrointestinal, urologic, and cardiac disorders; increased symmetry of Parkinsonism; and impairment of speech and swallowing (bulbar dysfunction).
Gastrointestinal dysfunction emerged as a surprisingly potent risk factor for dementia at an odds ratio of 2.28, just behind male gender, which had an odds ratio of 2.95. Urologic dysfunction was close behind at an odds ratio of 1.99. Increased symmetry of Parkinsonism conferred an odds ratio of 1.44. PIGD scores, at an odds ratio of 1.13, and total motor score, at 1.03, were less important risk factors in this population than previously believed, Dr. Uc said.
Baseline psychological tests such as total recall, delayed recall, and symbol-digit tests were, not surprisingly, the most important factors in predicting development of dementia, he continued.
“Subjects destined to be demented started out 1 standard deviation below normal,” he said.
Despite practice effects, which would be expected to improve their scores, “by 4 years they dropped off the cliff,” he said.
The average time-to-progression for dementia was 3.3 years after enrollment.
Demented subjects were more likely than other subjects to have a history of falls and gait disturbances, bulbar problems with speech, drooling and swallowing, and functional praxis (difficulties in writing, using utensils, dressing, personal hygiene functions, and turning in bed.)
Dr. Uc suggested that the multifaceted picture of dementia risk points to dysfunction in autonomic cholinergic neurotransmission as a promising target for diagnosis and prevention in patients with early-stage Parkinson's disease.