Richard P Mayeux

..Causes of variability in the measurement of biomarkers range from the individual to the laboratory. Issues that affect the analysis of biomarkers are discussed along with recommendations on how to deal with bias and confounding...

..Similarly, no association was found in the Caribbean Hispanic families for CH25H. However, we did observe a possible interaction between ABCA1 and APOE in the Hispanics...

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..Thus, there are several types of peripheral biomarkers under investigation, but more work is required before they can be deemed clinically useful...

..To compare the sensitivity and specificity of the clinical diagnosis of Alzheimer disease, the distribution of pathological causes, and the demographic and clinical characteristics of 2 different groups of patients with dementia...

..Alzheimer disease (AD) and stroke are common in elderly individuals, but the relation between these 2 disorders remains uncertain...

..The analysis of behavioral and genetic factors that may lower disease risk has led to clinical trials that are either in progress or being planned with the aim of preventing these disorders...

..Transgenic mice and elderly humans without AD or QD expressing APOE-epsilon4 show a decline in memory performance over time. These observations provide evidence for an APOE-specific effect on memory during senescence...

..In this issue, the JCI provides readers with a series dedicated to complex genetic disorders, offering a view of genetic medicine in the 21st century...

..74; P=.013). This study of Caribbean Hispanics with familial AD extends and provides modest evidence of linkage to loci on chromosome 12p. Linkage varied by age at onset of AD and by the presence or absence of the APOE-epsilon 4 allele...

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..Biomarkers for AD could also facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in "mixed dementia"...

..to investigate the relation of plasma lipids to all-cause mortality in a multi-ethnic cohort of non-demented elderly...

..The results of the present study identify phenotypes associated with preserved cognitive and functional abilities which may serve as markers for longevity...

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..To determine if plasma β-amyloid (Aβ) levels (1) can be linked to specific cognitive changes that constitute conversion to Alzheimer disease (AD) and (2) correspond to cognitive change independent of dementia...

..TP73 mRNA is transcribed from three promoters, termed P1-P3, and there is evidence for an additional complexity in its regulation, namely, a variable allelic expression bias in some human tissues...

..High-sensitivity C-reactive protein (hsCRP) is a biomarker of cardiovascular risk that is suggested to be a biomarker for cognitive impairment...

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..To investigate the association between Alzheimer disease (AD) and variant alleles in SORL1 using a series of single nucleotide polymorphisms (SNPs) in an urban, multiethnic, community-based population...

..To better understand the genetic influence on component phenotypes of AD, we estimated the heritability (h(2)) of abstract reasoning and examined its relation with apolipoprotein epsilon 4 (APOE-epsilon 4)...

..The metabolic syndrome (MeSy) may be related to Alzheimer's disease (AD). Our aims were to investigate the association of the MeSy with incident dementia in a multiethnic elderly cohort in the United States...

..Thus, further studies are needed to identify functional variants that influence risk for AD in this uniquely vulnerable population...

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

..CONCLUSION: Low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. More research is needed to understand these associations...

..Baseline data were collected from 1992 to 1994, follow-up data were collected at 18-month intervals...

..Furthermore, an association between ET and dementia has been reported in a single population-based study in Spain. This has not been confirmed elsewhere...

..Also, if MPS are a marker for developing Alzheimer-type changes, hippocampal volume on MRI might be diminished in individuals with MPS...

..These findings indicate that the predictive utility of olfactory identification deficits for decline from no MCI to MCI and AD needs to be assessed in longitudinal studies of elderly community samples...

..The validity of a self-reported stroke remains inconclusive...

..Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease (AD) risk but their combined association has not been investigated...

..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...

..Telephone-based interviews can be used for screening and to obtain key study outcomes when participants in longitudinal studies die or cannot be seen in person, but must be validated among ethnically and educationally diverse people...

..2) did not. These findings suggest that the increased risk of incident dementia in Parkinson's disease associated with age and severity of extrapyramidal signs is related primarily to their combined effect rather than separate effects...

..To reexamine the association of lipid levels with Alzheimer disease (AD) using Cox proportional hazards models...

..To develop a simple summary risk score for the prediction of Alzheimer disease in elderly persons based on their vascular risk profiles...

..Future trials are needed to determine whether alternate timing, dosage, formulation, or method of administration of hormone replacement can reduce the risk of dementia...

..Elevated blood pressure (BP) and fluctuation in BP may lead to cerebrovascular disease through ischemic changes and compromised cerebral autoregulation...

..Baseline MPS seems to be a predictor of incident dementia. These motor signs might, therefore, serve as a useful biomarker for emerging dementia...

..Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease...

..Higher adherence to the Mediterranean diet (MeDi) may protect from Alzheimer disease (AD), but its association with mild cognitive impairment (MCI) has not been explored...

..The elderly in whom these signs have been detected are 50% more likely to complain of poor balance and 90% more likely to require a cane, walker, or wheelchair than are their counterparts without these signs...

..Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD...

..The results of this study suggest that in an ethnically diverse cohort, literacy level should be considered as a mediator of the interactions of biological and environmental factors on cognitive decline...

..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...

..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...

..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...

..Our findings support the hypothesis that reductions in estrogen following menopause can contribute to the cascade of pathological processes leading to AD...

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..Two tightly linked polymorphisms (PvuII and XbaI) in the first intron of estrogen receptor 1 (ESR1), the gene for ER-alpha, have been reported to influence estrogen receptor expression and may influence the risk of AD...

..Individuals with Down syndrome have increased levels of beta-amyloid peptides and an increased risk for AD...

..To determine whether plasma homocysteine (Hcy) concentration is associated with mild parkinsonian signs (MPS) in community-dwelling elderly individuals...

..Identifying the genes associated with life span and survival will provide insight into how the genes interact with environment to influence aging in humans...

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..Missense mutations in the amyloid precursor protein (APP) gene cause early-onset Alzheimer disease (AD). However, little is known regarding the effects of polymorphisms in regulatory sequences of APP on AD susceptibility...

..The purpose of this study was to examine whether neuropsychological tests translated into Spanish measure the same cognitive constructs as the original English versions...

..We conclude that altered gene-specific DNA methylation is a recurrent and functionally relevant downstream response to trisomy 21 in human cells...

..Our results suggest individuals with elevated plasma Abeta42 are at increased risk of AD and that with the onset of disease, the decline in some forms of Abeta may reflect compartmentalization of Abeta peptides in the brain...

..This recurrent phenomenon of sequence-dependent ASM has practical implications for mapping and interpreting associations of noncoding SNPs and haplotypes with human phenotypes...

..Familial aggregation of dementia with Lewy bodies (DLB) remains unclear...

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..INTERPRETATION: Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease...

..Further we will make cells lines and clinical information available to others through the National Cell Repository for Alzheimer's Disease. ..

..background, significance, and innovation ..

..Identifying genes associated with ES will be an important step in understanding the processes underlying successful aging. ..

..The ultimate goal of this project is to chromosomally localize genes that may increase the risk of AD among the Caribbean Hispanic ethnic group. ..

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..Therefore the potential public health impact of developing reliable and valid biomarkers in a multi-ethnic community is a major benefit of this proposed investigation. ..