ABSTRACT
Parkinson's disease (PD) patients often develop dementia, and Alzheimer's disease (AD) patients frequently develop parkinsonian signs. The apolipoprotein E epsilon4 allele is associated with increased risk and earlier onset of AD. We studied 137 unrelated white PD patients. Those with epsilon4 had the earliest onset (52.7 +/- 9.8 years), epsilon3/epsilon3 patients had an intermediate onset (56.1 +/- 11.1 years), and those with epsilon2 had the latest onset (59.1 +/- 13.4 years). The age at onset distribution for epsilon4/epsilon- was significantly earlier than for epsilon3/epsilon3 and epsilon2/epsilon3. These preliminary results suggest that apolipoprotein E genotypes modulate the age at onset of PD.
Subject(s)
Age of Onset , Apolipoproteins E/genetics , Parkinson Disease/genetics , Aged , Apolipoprotein E2 , Apolipoprotein E3 , Apolipoprotein E4 , Female , Genotype , Humans , Male , Middle AgedABSTRACT
The oldest old are the fastest-growing segment of our population and have the highest prevalence of dementia. Little is known about the genetics of cognitive health in the very old. The aim of this study was to determine whether the genetic risk factors for Alzheimer disease (AD)--namely, apolipoprotein E (APOE) epsilon4 allele and a family history of dementia-continue to be important factors in the cognitive health of the very old. Case-control studies suggest that the effect of genetic factors diminishes at age >75 years. The present prospective study provided evidence to the contrary. We studied 114 Caucasian subjects who were physically healthy and cognitively intact at age 75 years and who were followed, for an average of 4 years, with neurological, psychometric, and neuroimaging examinations. Excellent health at entry did not protect against cognitive decline. Incidence of cognitive decline rose sharply with age. epsilon4 and a family history of dementia (independent of epsilon4) were associated with an earlier age at onset of dementia. Subjects who had epsilon4 or a family history of dementia had a ninefold-higher age-specific risk for dementia than did those who had neither epsilon4 nor a family history of dementia. These observations suggest that the rate of cognitive decline increases with age and that APOE and other familial/genetic factors influence the onset age throughout life.
Subject(s)
Aging/physiology , Alzheimer Disease/etiology , Apolipoproteins E/genetics , Brain/physiology , Cognition Disorders/etiology , Dementia/genetics , Age of Onset , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Apolipoprotein E4 , Cognition Disorders/genetics , Cross-Sectional Studies , Female , Gene Frequency , Genotype , Humans , Male , Oregon , Prospective Studies , Risk FactorsABSTRACT
The role of gender in the pathogenesis of Alzheimer's disease (AD) is an important issue that remains controversial. We compared men and women in late-onset familial AD kindreds for the risk of developing AD by studying 26 well-characterized familial AD kindreds from the Oregon Alzheimer Disease Center and, for confirmation, an additional 32 kindreds from the National Cell Repository (NCR) at the Indiana University Alzheimer Disease Center. Comparing women to men, the age-adjusted odds ratio estimates were 3.2 (p = 0.0002) for the Oregon data and 2.3 (p = 0.004) for the NCR data. These results suggest that gender is an independent risk factor for familial late-onset AD and may play a role in the pathogenesis of this disease.
