ABSTRACT
The frequency and clinical and pathological characteristics associated with the Gly206Ala presenilin 1 (PSEN1) mutation in Puerto Rican and non-Puerto Rican Hispanics were evaluated at the University of Pennsylvania's Alzheimer's Disease Center. DNAs from all cohort subjects were genotyped for the Gly206Ala PSEN1 mutation. Carriers and non-carriers with neurodegenerative disease dementias were compared for demographic, clinical, psychometric, and biomarker variables. Nineteen (12.6%) of 151 unrelated subjects with dementia were discovered to carry the PSEN1 Gly206Ala mutation. Microsatellite marker genotyping determined a common ancestral haplotype for all carriers. Carriers were all of Puerto Rican heritage with significantly younger age of onset, but otherwise were clinically and neuropsychologically comparable to those of non-carriers with AD. Three subjects had extensive topographic and biochemical biomarker assessments that were also typical of non-carriers with AD. Neuropathological examination in one subject revealed severe, widespread plaque and tangle pathology without other meaningful disease lesions. The PSEN1 Gly206Ala mutation is notably frequent in unrelated Puerto Rican immigrants with dementia in Philadelphia. Considered together with the increased prevalence and mortality of AD reported in Puerto Rico, these high rates may reflect hereditary risk concentrated in the island which warrants further study.
Subject(s)
Alanine/genetics , Dementia/genetics , Glycine/genetics , Hispanic or Latino/genetics , Mutation/genetics , Presenilin-1/genetics , Aged , Aged, 80 and over , Dementia/ethnology , Dementia/pathology , Female , Gene Frequency/genetics , Genetic Carrier Screening , Hispanic or Latino/ethnology , Humans , Male , Middle Aged , Philadelphia/ethnology , Puerto Rico/ethnologyABSTRACT
OBJECTIVE: To compare presentation of Alzheimer disease (AD) at the time of initial evaluation at a university specialty clinic across three ethnoracial groups in order to understand similarities and differences in the demographic, clinical, cognitive, psychiatric, and biologic features. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 1,341 self-identified African American, Latino (primarily of Caribbean origin), and white non-Hispanic ("WNH") subjects were recruited from primary care sites or by referral by primary care physicians. MEASUREMENTS: Demographic variables and age of onset of AD, as well as cognitive, functional, and mood impairments at the time of initial presentation and frequencies of apolipoprotein E genotypes, were compared across groups. RESULTS: Differences among ethnoracial groups were found for nearly all variables of interest. In particular, the largely immigrant Puerto Rican Latino group had an earlier age of onset of AD, more cognitive impairment, and greater severity of cognitive impairment at the time of initial evaluation in the setting of low average education and socioeconomic status. There was more depression in the Latinos compared with African Americans and WNHs. Greater severity of symptoms was not accounted for by a difference in lag time between onset of symptoms and initial evaluation. The apolipoprotein E-4 genotype was not associated with AD in the Latino cohort. CONCLUSIONS: Minority groups in Philadelphia, especially Latinos, exhibit a more severe profile of AD at the time of presentation than WNHs. Important potential confounds need to be considered and future research comparing immigrant and nonimmigrant Latino groups will be necessary to elucidate the highly significant differences reported.
Subject(s)
Alzheimer Disease/ethnology , Apolipoprotein E4/genetics , Cognition Disorders/ethnology , Depression/ethnology , Black or African American/genetics , Black or African American/psychology , Age of Onset , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Alzheimer Disease/psychology , Caribbean Region/ethnology , Case-Control Studies , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/genetics , Cognition Disorders/psychology , Cross-Sectional Studies , Depression/diagnosis , Depression/epidemiology , Depression/genetics , Depression/psychology , Female , Genotype , Hispanic or Latino/genetics , Hispanic or Latino/psychology , Hospitals, Urban , Humans , Male , Neuropsychological Tests , Philadelphia/epidemiology , Psychiatric Status Rating Scales , Risk Factors , Severity of Illness Index , Sex Distribution , Socioeconomic Factors , White People/genetics , White People/psychologyABSTRACT
BACKGROUND: Latino individuals are the largest minority group and the fastest growing population group in the United States, yet there are few studies comparing the clinical features of Alzheimer disease (AD) in this population with those found in Anglo (white non-Latino) patients. OBJECTIVE: To compare the age at AD symptom onset in Latino and Anglo individuals. DESIGN: Cross-sectional assessment using standardized methods to collect and compare age at AD symptom onset, demographic variables, and medical variables. SETTING: Five National Institute on Aging-sponsored Alzheimer's Disease Centers with experience evaluating Spanish-speaking individuals. PATIENTS: We evaluated 119 Latino and 55 Anglo patients who had a diagnosis of AD. MAIN OUTCOME MEASURE: Age at symptom onset. RESULTS: After adjusting for center, sex, and years of education, Latino patients had a mean age at symptom onset 6.8 years earlier (95% confidence interval, 3.5-10.3 years earlier) than Anglo patients. CONCLUSIONS: An earlier age at symptom onset suggests that US mainland Latino individuals may experience an increased burden of AD compared with Anglo individuals. The basis for the younger age at symptom onset remains obscure.
