Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics.

Background: The primary effect of the apolipoprotein E epsilon4 (APOE epsilon4) allele is on the age at onset of Alzheimer disease (AD).

Objective: To investigate whether the presence of the APOE epsilon4 allele can account for the earlier age at onset of familial AD (FAD) compared with sporadic AD (SAD).

Design: Population-based, case series ascertained in a prospective study of aging and dementia in Medicare recipients aged 65 years or older.

Bioavailable estradiol and age at onset of Alzheimer's disease in postmenopausal women with Down syndrome.

Several lines of evidence suggest that loss of estrogen after menopause may play a role in the cognitive declines associated with Alzheimer's disease (AD). Women with Down syndrome (DS) experience early onset of both menopause and AD. This timing provides a model to examine the influence of endogenous estrogen deficiency on risk of AD.

Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia.

Objective: Reduced telomere length may be a marker of biological aging. We hypothesized that telomere length might thus relate to increased risk for dementia and mortality.

Methods: This nested case-control study used stored leukocyte DNA from 257 individuals (mean age, 81.

Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21.

Background: Down syndrome (DS) is caused by trisomy 21 (+21), but the aberrations in gene expression resulting from this chromosomal aneuploidy are not yet completely understood.

Methods: We used oligonucleotide microarrays to survey mRNA expression in early- and late-passage control and +21 fibroblasts and mid-gestation fetal hearts. We supplemented this analysis with northern blotting, western blotting, real-time RT-PCR, and immunohistochemistry.

Cognitive decline and literacy among ethnically diverse elders.

Researchers on genetic and environmental influences on risk for Alzheimer's disease must be prepared for the growing ethnic and racial diversity of our participants. Within the investigation, years of education has typically served as a proxy for cognitive reserve, which may be one factor in influencing risk of cognitive decline among aging people. However, among ethnic minorities, years of education is a poor reflection of the value of educational experience and native ability.

Implementing diagnostic criteria and estimating frequency of mild cognitive impairment in an urban community.

Background: Reported rates of mild cognitive impairment (MCI) range widely depending on methodologic differences, including specific sample characteristics, cognitive measures used, normative samples used for neuropsychological tests, and diagnostic criteria.

Objectives: To operationalize diagnostic criteria for MCI and examine the frequency of MCI in ethnically and linguistically diverse elders (individuals older than 65 years).

Design: Prospective, community-based longitudinal cohort study.

Decline in cognitive and functional skills increases mortality risk in nondemented elderly.

Objective: To investigate the relation between rate of decline in cognitive and functional/physical abilities and risk of death in nondemented elderly.

Methods: Data were included from individuals participating in a prospective study of aging and dementia in Medicare recipients, 65 years and older, residing in northern Manhattan. The authors included 878 members of the cohort who had measures of memory, cognitive, language, or functional scores over three study intervals, excluding all participants who were demented or had more than one problem in activity of daily living (ADL) skills at baseline.

Functional correlates of mild parkinsonian signs in the community-dwelling elderly: poor balance and inability to ambulate independently.

Mild tremor, rigidity, and bradykinesia (mild parkinsonian signs, MPS) are commonly detected during the clinical examination of elderly people without known neurological disease. The functional correlates of these incidental findings are not well understood. Balance and ability to ambulate independently are important functions in the elderly.

Unbalanced placental expression of imprinted genes in human intrauterine growth restriction.

Imprinted genes control fetal and placental growth in mice and in rare human syndromes, but the role of these genes in sporadic intrauterine growth restriction (IUGR) is less well-studied. We measured the ratio of mRNA from a maternally expressed imprinted gene, PHLDA2, to that from a paternally expressed imprinted gene, MEST, by Northern blotting in 38 IUGR-associated placentae and 75 non-IUGR placentae and found an increase in the PHLDA2/MEST mRNA ratio in IUGR (p=0.0001).

Mortality is associated with apolipoprotein E epsilon4 in nondemented adults with Down syndrome.

Apolipoprotein E genotype has been related to survival in the general population, but its strong association with Alzheimer's disease (AD) makes interpretation of findings difficult. Previous studies of adults with Down syndrome (DS) have consistently found that the presence of the apolipoprotein E epsilon2 allele increases longevity and reduces the risk of dementia, while the apolipoprotein E epsilon4 allele increases risk for dementia. In contrast, reduced frequencies of the apolipoprotein E epsilon4 allele among elderly groups have been reported, suggesting that the epsilon4 allele may be associated with early mortality in this population.

Telomere shortening in T lymphocytes of older individuals with Down syndrome and dementia.

Telomere shortening has been recently correlated with Alzheimer's disease status. Therefore, we hypothesized that a possible association might exist for adults with Down syndrome (DS). Using blind, quantitative telomere protein nucleic acid FISH analyses of metaphase and interphase preparations from 18 age-matched trisomy 21 female study participants with and without dementia, we have observed increased telomere shortening in adults with DS and dementia (p < .

Association between mild parkinsonian signs and mild cognitive impairment in a community.

Background: Mild parkinsonian signs (MPS) are associated with prevalent and incident dementia but it is not known whether they are associated with mild cognitive impairment (MCI).

Objective: To determine whether MPS and specific MPS (changes in axial function, rigidity, tremor) are associated with MCI in nondemented community-dwelling older people in northern Manhattan, NY.

Methods: Participants underwent neurologic assessment, including a modified motor portion of the Unified Parkinson Disease Rating Scale.

Dementia of the Alzheimer's type and accelerated aging in Down syndrome.

This case study, of a woman with Down syndrome and dementia of the Alzheimer's type (DAT), follows the course of her decline over an 11-year period until death at age 57. Detailed neuropathological findings are also presented. This case illustrates features of premature aging that are typically associated with Down syndrome, and the progressive changes in memory and cognition that are usually associated with DAT.

Functional correlates and prevalence of mild parkinsonian signs in a community population of older people.

Background: Mild parkinsonian signs (MPS) are associated with incident dementia and an increased risk of mortality. To our knowledge, the functional correlates of MPS have not been studied.

Objectives: To study the functional correlates of MPS, including self-reported and performance-based measures of function, and to determine the prevalence of MPS in a cohort of community-dwelling older people (aged >or=65 years).

Relationship between plasma lipids and all-cause mortality in nondemented elderly.

Objectives: To investigate the relationship between plasma lipids and risk of death from all causes in nondemented elderly.

Design: Prospective cohort study.

Setting: Community-based sample of Medicare recipients, aged 65 years and older, residing in northern Manhattan.

Preservation of cognitive and functional ability as markers of longevity.

Longevity is a complex biological process for which the phenotypes have not been established. Preservation of cognitive and physical function may be important and preservation of these functions is, in part, inherited. We investigated the relation between rate of change in cognitive and functional abilities in probands and risk of death in their siblings.

Genetic influences on life span and survival among elderly African-Americans, Caribbean Hispanics, and Caucasians.

An investigation of the genetic influences on life span and survival was conducted among elderly African-Americans, Caribbean Hispanics, and Caucasians Medicare recipients (ages 65-104 years). Family history information on 13,161 parents and siblings was obtained. Heritability of life span varied by the age and by ethnic group being lowest for African-Americans.

Incidence and prevalence of dementia in elderly adults with mental retardation without down syndrome.

Rates of dementia in adults with mental retardation without Down syndrome were equivalent to or lower than would be expected compared to general population rates, whereas prevalence rates of other chronic health concerns varied as a function of condition. Given that individual differences in vulnerability to Alzheimer's disease have been hypothesized to be due to variation in cognitive reserve, adults with mental retardation, who have long-standing intellectual and cognitive impairments, should be at increased risk. This suggests that factors determining intelligence may have little or no direct relationship to risk for dementia and that dementia risk for individuals with mental retardation will be comparable to that of adults without mental retardation unless predisposing risk factors for dementia are also present.

Dementia in adults with mental retardation: assessment at a single point in time.

Dementia status of 273 adults with mental retardation was rated based upon two extensive evaluations conducted 18 months apart. Overall, 184 individuals did not have dementia, 33 had possible or definite dementia, and 66 had findings suggesting uncertain or questionable status. These ratings were compared to binary classifications (dementia vs.

Obesity enhances verbal memory in postmenopausal women with Down syndrome.

Several lines of evidence suggest that the loss of estrogen after menopause may play a role in cognitive declines associated with Alzheimer's disease (AD). In postmenopausal women, the principal source of estrogen is estrone, which is influenced by body mass index (BMI). Increased BMI in postmenopausal women is associated with higher levels of serum estradiol and estrone.

Plasma A[beta]40 and A[beta]42 and Alzheimer's disease: relation to age, mortality, and risk.

Background: Plasma amyloid [beta]-peptide (A[beta]) 40 and A[beta]42 levels are increased in persons with mutations causing early-onset familial Alzheimer's disease (AD). Plasma A[beta]42 levels were also used to link microsatellite genetic markers to a putative AD genetic locus on chromosome 10 and were observed in patients with incipient sporadic AD.

Methods: The authors measured plasma A[beta]40 and A[beta]42 levels using a sandwich ELISA after the initial examination of 530 individuals participating in an epidemiologic study of aging and dementia.

Onset of dementia is associated with age at menopause in women with Down's syndrome.

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system.

Combined effect of age and severity on the risk of dementia in Parkinson's disease.

Age and severity of extrapyramidal signs have been consistently associated with incident dementia in Parkinson's disease. We evaluated the separate and combined effects of age and severity of extrapyramidal signs on the risk of incident dementia in Parkinson's disease in the setting of a population-based prospective cohort study. Age and the total Unified Parkinson's Disease Rating Scale motor score at baseline evaluation were dichotomized at the median.

Genetic and host factors for dementia in Down's syndrome.

Background: The high risk for dementia in adults with Down's syndrome has been attributed to triplication and overexpression of the gene for amyloid precursor protein (APP). But the wide variation in age at onset must be due to other risk factors.

Aims: To identify factors which influence age at onset of dementia in Down's syndrome.