Medline ® Abstract for Reference 3
of 'Clinical features and diagnosis of Alzheimer disease'
3
TI
Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis.
AU
Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, Goate A, Frommelt P, Ghetti B, Langbaum JB, Lopera F, Martins R, Masters CL, Mayeux RP, McDade E, Moreno S, Reiman EM, Ringman JM, Salloway S, Schofield PR, Sperling R, Tariot PN, Xiong C, Morris JC, Bateman RJ, Dominantly Inherited Alzheimer Network
SO
Neurology. 2014;83(3):253. Epub 2014 Jun 13.
OBJECTIVE:
To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD.
METHODS:
We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study.
RESULTS:
We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p<10(-16), r2>0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex.
CONCLUSIONS:
Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
AD
From the Departments of Neurology (D.C.R., J.C.M., R.J.B.), Biostatistics (C.X.), and Psychiatry (A.G.), Washington University School of Medicine, St. Louis, MO; Neurologische Klinik Ludwig-Maximilians-Universität Munich and German Center for Neurodegenerative Diseases (A.D.), Munich, Germany; Department of Neurosciences (P.S.A.), University of California San Diego; Mental Health Research Institute (C.L.M.), University of Melbourne, Australia; Grupo de Neurociencias de Antioquia (N.A.-B., F.L., S.M.), Universidad de Antioquia, Medellín, Colombia; Department of Neurology (E.M.), University of Pittsburgh, PA; Department of Neurology (T.B.), University of Washington, Seattle; Banner Alzheimer's Institute (J.B.S.L., E.M.R., P.N.T.), Phoenix, AZ; Neuroscience Research Australia and University of New South Wales (P.R.S.), Sydney, Australia; Edith Cowan University (R.M.), Western Australia; Easton Center for Alzheimer's Disease Research at UCLA (J.M.R.), Los Angeles, CA; Department of Neurolo
PMID