[Accepted Manuscript] Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study.


Kinnunen, K.M.; Cash, D.M.; Poole, T.; Frost, C.; Benzinger, T.L.S.; Ahsan, R.L.; Leung, K.K.; Cardoso, M.J.; Modat, M.; Malone, I.B.; Morris, J.C.; Bateman, R.J.; Marcus, D.S.; Goate, A.; Salloway, S.; Correia, S.; Sperling, R.A.; Chhatwal, J.P.; Mayeux, R.; Brickman, A.M.; Martins, R.N.; Farlow, M.R.; Ghetti, B.; Saykin, A.J.; Jack, C.R. Jr; Schofield, P.R.; McDade, E.; Weiner, M.W.; Ringman, J.M.; Thompson, P.M.; Masters, C.L.; Rowe, C.C.; Rossor, M.N.; Ourselin, S.; Fox, N.C.; Dominantly Inherited Alzheimer Network (DIAN), .; (2017) [Accepted Manuscript] Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study. Alzheimer's & dementia. ISSN 1552-5260 DOI: https://doi.org/10.1016/j.jalz.2017.06.2268

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Abstract

Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Medical Statistics
Faculty of Public Health and Policy > Dept of Social and Environmental Health Research
URI: http://researchonline.lshtm.ac.uk/id/eprint/4121204

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