Parkinsonianlike signs and risk of incident Alzheimer disease in older persons

Background: Parkinsonianlike signs are common in older persons, but little is known about how their severity or rate of progression is related to the development of Alzheimer disease (AD) or decline in cognition. Objective: To examine the association of progression of parkinsonianlike signs with incident AD and cognitive decline. Design: Longitudinal cohort study. Participants and Setting: For up to 8 years, 824 older Catholic clergy members without clinical evidence of AD or Parkinson disease at baseline underwent annual clinical evaluations that included a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS), detailed cognitive function testing,,and clinical classification of AD. Main Outcome Measures: Clinically diagnosed AD and change in global and specific measures of cognitive function. Results: During an average of 4.6 years of observation, 114 persons developed AD. The global UPDRS score increased in 79% of participants, who were divided into tertiles with the least, moderate, or most rapid progression. We examined the relationship of progression to disease risk in a proportional hazards model that controlled for baseline global UPDRS and demographic variables. Compared with the 21% without progression, risk of AD more than doubled in the subgroup with the least progression (P=.08), more than tripled in the moderate subgroup (P=.02), and increased more than 8-fold in the subgroup with the most rapid progression (P<.001). This effect was mainly due to worsening gait and rigidity. Rate of change on the global UPDRS measure was inversely correlated with rate of change on a global measure of cognitive function (r=-0.64). Conclusion: Progression of parkinsonianlike signs in old age is associated with decline in cognitive function and the development of AD.