Children of Persons With Alzheimer Disease

Jarvik, Lissy F.; LaRue, Asenath; Blacker, Deborah; Gatz, Margaret; Kawas, Claudia H.; McArdle, John J.; Morris, John C.; Mortimer, James A.; Ringman, John M.; Ercoli, Linda M.; Gokhman, Izabella; Manly, Jennifer J.; Plassman, Brenda L.; Rasgon, Natalie; Roberts, J. Scott; Sunderland, Trey; Swan, Gary E.; Wolf, P. A.; Zonderman, Alan B.

doi:10.1097/wad.0b013e31816653ac

Cited by 25 publications

(27 citation statements)

References 199 publications

(212 reference statements)

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“…The development and clinical expression of AD most likely reflect a complex interplay of genetic and environmental factors that research is only beginning to address (Jarvik et al, 2008). WRAP is one of only a handful of studies that offer the opportunity to examine genetic and environmental interactions prospectively.…”

Section: Discussionmentioning

confidence: 99%

“…There is also little known about how potentially modifiable risk factors such as education, occupation, or cognitive leisure activity might interact with genetic susceptibility for AD (Jarvik et al, 2008; Lee, 2003). Having an apolipoprotein allele 4 (APOE-ε4) and/or a family history of AD in a first-degree relative both increase risk of developing the disease (Cupples et al, 2004; Lautenschlager et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Cognitive activities and cognitive performance in middle-aged adults at risk for Alzheimer’s disease.

Jonaitis

Rue

Mueller

et al. 2013

Psychology and Aging

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Cognitive activity is thought to provide some protection against dementia, but the mechanism and timing of these effects are unknown. Data for this study were drawn from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), an at-risk middle-aged sample (mean age = 54 years) enriched for parental family history of Alzheimer’s disease (AD). We had two main aims: (1) to determine the relative contribution of three facets of cognitive activity -- education, occupational complexity with data, and cognitive leisure activities – to WRAP participants’ cognitive performance; and (2) to assess for interactions between genetic risk factors and cognitive activity in explaining cognitive performance. Results from mixed effects models indicate that some of the variance usually attributed to education may be more closely accounted for by cognitive activities later in life. Overall, our analyses suggest cautious optimism for cognitive activities, especially game-playing, as a strategy for preserving cognitive strengths in midlife.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cognitive activities and cognitive performance in middle-aged adults at risk for Alzheimer’s disease.

Jonaitis

Rue

Mueller

et al. 2013

Psychology and Aging

View full text Add to dashboard Cite

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“…First degree familial history of AD has been shown to increase risk of developing AD by as much as 10 fold (Silverman et al 2005; Jarvik et al 2008). Furthermore, this risk factor is associated with alterations in brain perfusion, as cognitively normal middle-aged adults with a familial history of AD demonstrate decreased CBF in right superior and middle frontal cortices, compared to those without a familial history (Okonkwo et al 2014).…”

Section: Resting Cbf In Familial Riskmentioning

confidence: 99%

The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer’s Disease

2016

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There is accumulating evidence suggesting that changes in brain perfusion are present long before the clinical symptoms of Alzheimer’s disease (AD), perhaps even before amyloid-β accumulation or brain atrophy. This evidence, consistent with the vascular hypothesis of AD, implicates cerebral blood flow (CBF) in the pathogenesis of AD and suggests its utility as a biomarker of preclinical AD. The extended preclinical phase of AD holds particular significance for disease-modification, as treatment would likely be most effective in this early asymptomatic stage of disease. This highlights the importance of identifying reliable and accurate biomarkers of AD that can differentiate normal aging from preclinical AD prior to clinical symptom manifestation. Cerebral perfusion, as measured by arterial spin labeling magnetic resonance imaging (ASL-MRI), has been shown to distinguish between normal controls and adults with AD. In addition to demonstrating diagnostic utility, CBF has shown usefulness as a tool for identifying those who are at risk for AD and for predicting subtle cognitive decline and conversion to mild cognitive impairment (MCI) and AD. Taken together, this evidence not only implicates CBF as a useful biomarker for tracking disease severity and progression, but also suggests that ASL-measured CBF may be useful for identifying candidates for future AD treatment trials, especially in the preclinical, asymptomatic phases of the disease.

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“…Another major risk factor is family history (FH), particularly when it involves the parents 2-3 and young age of onset 4-5 . Much of the FH risk has been attributed to the e4 allele of the apolipoprotein E (APOE) genotype 6 .…”

Section: Introductionmentioning

confidence: 99%

Multiple imputation of a randomly censored covariate improves logistic regression analysis

Atem

Qian

Maye

et al. 2016

Journal of Applied Statistics

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Randomly censored covariates arise frequently in epidemiologic studies. The most commonly used methods, including complete case and single imputation or substitution, suffer from inefficiency and bias. They make strong parametric assumptions or they consider limit of detection censoring only. We employ multiple imputation, in conjunction with semi-parametric modeling of the censored covariate, to overcome these shortcomings and to facilitate robust estimation. We develop a multiple imputation approach for randomly censored covariates within the framework of a logistic regression model. We use the non-parametric estimate of the covariate distribution or the semiparametric Cox model estimate in the presence of additional covariates in the model. We evaluate this procedure in simulations, and compare its operating characteristics to those from the complete case analysis and a survival regression approach. We apply the procedures to an Alzheimer's study of the association between amyloid positivity and maternal age of onset of dementia. Multiple imputation achieves lower standard errors and higher power than the complete case approach under heavy and moderate censoring and is comparable under light censoring. The survival regression approach achieves the highest power among all procedures, but does not produce interpretable estimates of association. Multiple imputation offers a favorable alternative to complete case analysis and ad hoc substitution methods in the presence of randomly censored covariates within the framework of logistic regression.

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Children of Persons With Alzheimer Disease

Cited by 25 publications

References 199 publications

Cognitive activities and cognitive performance in middle-aged adults at risk for Alzheimer’s disease.

Cognitive activities and cognitive performance in middle-aged adults at risk for Alzheimer’s disease.

The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer’s Disease

Multiple imputation of a randomly censored covariate improves logistic regression analysis

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