Risk of dementia in relatives of patients with Alzheimer's disease

Huff, F. Jacob; Auerbach, Jonathan; Chakravarti, Aravinda; Boller, François

doi:10.1212/wnl.38.5.786

Cited by 101 publications

(50 citation statements)

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“…Re-analysis of these data pooled with data from another study [573] gave similar results (RR 2.4, 95% CI 1.0-5.8) [574]. Other studies, however, reported no increased risk of PD in relatives of patients with Alzheimer's disease [575][576][577][578], although two of these were small, including only 70 [576] and 98 [577] Alzheimer cases.…”

Section: Dementiasupporting

confidence: 52%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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Section: Dementiasupporting

confidence: 52%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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“…The telephone assessments included a review of the items on the Family History Form of Huff and colleagues 27 and a survey of the subjects' activities of daily living. Subjects and their identified 'best' informants were encouraged to contact the research nurse if any evidence of a change in mental functioning occurred during the interim.…”

Section: Longitudinal Surveillance Protocolmentioning

confidence: 99%

“…Subject selection was designed to include individuals who represented a wide age range so that the effects of age-specific risk factors would be observable. By recruiting a cohort of individuals whose overall incidence rate of developing AD would be expected to be several-fold higher than that in a community sample by virtue of their family history, [24][25][26][27] we anticipated that the overall number of subject-years of follow-up required to detect risk factors that had at least moderate-sized effects would be feasible. Transformed cell lines from these individuals were established so that the effects of genetic polymorphisms or mutations that modulate the age-specific risk of developing AD could be evaluated.…”

Section: Introductionmentioning

confidence: 99%

D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals

2001

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Typical, later-onset forms of Alzheimer's disease (AD) appear to be influenced by multiple susceptibility loci, combinations of which contribute to the development of this disorder. We previously reported the results of a systematic survey of the human genome for the identification of highly informative DNA polymorphisms (SSTRPs) that target new AD risk genes. In addition to the APOE locus, our survey detected five new candidate susceptibility loci for AD, including D10S1423. An association of the D10S1423 234-bp allele with AD has been reported in three independent samples of AD cases and controls (Boston, Pittsburgh, Bonn). Data from our case-control studies suggest a strong synergistic interaction between the D10S1423 234-bp and APOE E4 risk alleles (234-bp carrier: OR = 2.5, 95% CI = 1.4-4.5; E4 carrier: OR = 8.3, 95% CI = 4.3-15.8; both alleles: OR = 23.1, 95% CI = 5.3-99.5). This report describes the prospective, longitudinal, double-blind assessment of the age-specific risk of AD encountered by 325 asymptomatic first-degree relatives of AD probands who carried the D10S1423 234-bp allele, the APOE E4 allele, or both, after 11.5 years of systematic follow-up. A total of 18 incident cases of AD were detected during the first 3379 subject-years of this longitudinal study. The effects of carrying either or both of the D10S1423 234-bp and APOE E4 alleles on the age-specific risk of developing AD were determined using Kaplan-Meier survival analysis. The age-specific risk of developing AD was the greatest for individuals who carried both alleles (Mantel-Cox statistic = 20.12, df = 3, P = 0.0002; Breslow statistic = 13.36, df = 3, P = 0.004). Cox proportional hazards models were developed to estimate the risk ratios for each genotype, controlling for the potential effects of age at recruitment, sex, and years of education. In the resulting best fitting model, only individuals who carried both risk alleles exhibited a risk ratio that differed significantly from 1 (risk ratio = 16.2, P = 0.008, 95% CI = 2.1-128.3). After controlling for these genotypes, female gender was also significantly associated with increased risk of developing AD (risk ratio = 5.1, P = 0.02, 95% CI = 1.2-21.1). Neither age at recruitment nor years of education made significant contributions to the model. Molecular Psychiatry (2001) 6, 413-419.

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“…In all cases, the risk for AD was higher in families with a history of AD, and the risk for PD was higher in families with a history of PD [19][20][21]34]. These same studies also failed to find any crossed risk of AD or PD using intergroup analyses.…”

Section: Discussionmentioning

confidence: 83%

“…Evidence for a 'shared-risk' has been mixed with most research finding no such increased crossed familial risk, although two of these studies nearly reached significance [19][20][21][22][23]. These studies grouped all AD cases together and all PD cases together and/or excluded patients with PD and dementia.…”

Section: Introductionmentioning

confidence: 99%

Evidence of shared risk for Alzheimer’s disease and Parkinson’s disease using family history

et al. 2007

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This case-control study examined the potential for a common etiology of Parkinson's disease (PD) and Alzheimer's disease (AD) using reported family history. Structured interviews were used to collect AD and PD family history from subjects (n=1531) with AD, PD, AD/PD, or controls. Intergroup analysis compared reported AD and PD family histories in the three case groups to the histories reported in the control group. Intragroup analysis stratified each diagnostic group based on positive family history of AD, then compared the subgroups for a family history of PD. Subjects with AD had a higher risk of having a family history of AD [odds ratio (OR) 2.3; 1.5-3.4] and subjects with PD had a higher risk of having a family history of PD (OR 2.2; 1.2-4.0) as compared to control subjects. Intergroup analyses revealed no significant crossed risk, increased risk of subjects with AD having a family history of PD vs controls and vice versa. Intragroup analysis found that subjects with PD and a family history of AD were more likely to have a family history of PD (OR 1.7; 1.1-2.6) when compared to subjects with PD and no family history of AD. A similar trend was found for subjects with AD (OR 1.7; 0.9-3.1). AD and PD cases each have an increased familial risk of their respective disease. Probands with AD or PD and a family history of either disease have a higher crossed risk of a family history of the other disease. These findings suggest the existence of common genetic and/or environmental factors that predispose to both AD and PD in the subset of cases with positive family history of both neurodegenerative diseases.

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Risk of dementia in relatives of patients with Alzheimer's disease

Cited by 101 publications

References 0 publications

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals

Evidence of shared risk for Alzheimer’s disease and Parkinson’s disease using family history

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