Alzheimer Disease: McArdle JJ

Jarvik L, LaRue A, Blacker D, Gatz M, Kawas C, McArdle JJ, Morris JC, Mortimer JA, Ringman JM, Ercoli L, Freimer N, Gokhman I, Manly JJ, Plassman BL, Rasgon N, Roberts JS, Sunderland T, Swan GE, Wolf PA, Zonderman AB. · Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA. · Alzheimer Dis Assoc Disord. · Pubmed #18317242 No free full text.

Abstract: Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the state of knowledge with respect to risk and protective factors for AD and recommend a research agenda with special emphasis on AD offspring.

Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB, Burke JR, Hurd MD, Potter GG, Rodgers WL, Steffens DC, McArdle JJ, Willis RJ, Wallace RB. · Duke University Medical Center, Durham, North Carolina 27701, USA. · Ann Intern Med. · Pubmed #18347351 links to  free full text

Abstract: BACKGROUND: Cognitive impairment without dementia is associated with increased risk for disability, increased health care costs, and progression to dementia. There are no population-based prevalence estimates of this condition in the United States. OBJECTIVE: To estimate the prevalence of cognitive impairment without dementia in the United States and determine longitudinal cognitive and mortality outcomes. DESIGN: Longitudinal study from July 2001 to March 2005. SETTING: In-home assessment for cognitive impairment. PARTICIPANTS: Participants in ADAMS (Aging, Demographics, and Memory Study) who were age 71 years or older drawn from the nationally representative HRS (Health and Retirement Study). Of 1770 selected individuals, 856 completed initial assessment, and of 241 selected individuals, 180 completed 16- to 18-month follow-up assessment. MEASUREMENTS: Assessments, including neuropsychological testing, neurologic examination, and clinical and medical history, were used to assign a diagnosis of normal cognition, cognitive impairment without dementia, or dementia. National prevalence rates were estimated by using a population-weighted sample. RESULTS: In 2002, an estimated 5.4 million people (22.2%) in the United States age 71 years or older had cognitive impairment without dementia. Prominent subtypes included prodromal Alzheimer disease (8.2%) and cerebrovascular disease (5.7%). Among participants who completed follow-up assessments, 11.7% with cognitive impairment without dementia progressed to dementia annually, whereas those with subtypes of prodromal Alzheimer disease and stroke progressed at annual rates of 17% to 20%. The annual death rate was 8% among those with cognitive impairment without dementia and almost 15% among those with cognitive impairment due to medical conditions. LIMITATIONS: Only 56% of the nondeceased target sample completed the initial assessment. Population sampling weights were derived to adjust for at least some of the potential bias due to nonresponse and attrition. CONCLUSION: Cognitive impairment without dementia is more prevalent in the United States than dementia, and its subtypes vary in prevalence and outcomes.

Blacker D, Lee H, Muzikansky A, Martin EC, Tanzi R, McArdle JJ, Moss M, Albert M. · Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, USA. · Arch Neurol. · Pubmed #17562935 links to  free full text

Abstract: OBJECTIVE: To examine neuropsychological measures among normal individuals that predict time to subsequent cognitive decline. DESIGN: Cognitive performance, as measured by 6 neuropsychological tests, was examined at baseline. Participants were followed up for approximately 5 years. Cox proportional hazards models were used to evaluate the neuropsychological measures at baseline that predicted time to progression from normal cognition to mild impairment. Comparable data also examined time to progression from mild impairment to a diagnosis of Alzheimer disease. SETTING: Community volunteer-based sample examined at a medical institution. PARTICIPANTS: One hundred and seven individuals who were cognitively normal and 235 individuals with mild cognitive impairment at baseline. MAIN OUTCOME MEASURES: Time to progression from normal cognition to mild impairment and time to progression from mild impairment to a diagnosis of Alzheimer disease. RESULTS: The risk of progressing from normal to mild impairment was considerably greater among those with lower scores on tests of episodic memory (eg, hazard ratio for a 1-SD decrease in the California Verbal Learning Test, 0.55; P<.001). Normal individuals who carried at least 1 copy of the apolipoprotein E epsilon2 allele were less likely to develop cognitive impairments over time than individuals with no epsilon2 allele (hazard ratio for presence of allele, 0.13; P = .006). Measures of both episodic memory and executive function were significant predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease (eg, hazard ratio for a 1-SD decrease in California Verbal Learning Test score, 0.67; P = .005; hazard ratio for a 1-SD increase in the time to complete part B of the Trail Making test, 1.40; P = .007). Among individuals with mild impairments, the apolipoprotein E epsilon4 allele increased risk for Alzheimer disease in a dose-dependent manner; however, this effect was not significant within the context of multivariable models. CONCLUSIONS: Episodic memory performance among normal individuals predicts time to progression to mild impairment while apolipoprotein E epsilon2 status is associated with lower risk of cognitive decline among normal individuals. Tests of both episodic memory and executive function are predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease.

McArdle JJ, Small BJ, Bäckman L, Fratiglioni L. · Department of Psychology, University of Southern California, Los Angeles 90089, USA. · J Geriatr Psychiatry Neurol. · Pubmed #16306246 No free full text.

Abstract: This article explores new statistical methodologies for using longitudinal data in the early prediction of Alzheimer's disease (AD). Specifically, the authors examine some new techniques that allow the joint or "shared" estimation of longitudinal components based on both duration (survival) and quantitative changes (growth curves). These new shared growth-survival parameter models may be used to characterize the declining functions that anticipate the onset of AD. The authors apply these models to data from the Kungsholmen Project, a longitudinal study of aging in Stockholm, Sweden. They examine age-based survival-frailty models for the onset of AD, latent growth-decline curve models for changes in cognition over age, and 3 alternative forms of models for the shared relationships of survival and early cognitive decline. The accuracy and reliability of this approach is considered for a better understanding of the developmental course of AD in these data, including the potential removal of biases due to subject selection.