David S Knopman1, Clifford R Jack2, Heather J Wiste2, Stephen D Weigand2, Prashanthi Vemuri2, Val J Lowe2, Kejal Kantarci2, Jeffrey L Gunter2, Matthew L Senjem2, Michelle M Mielke2, Mary M Machulda2, Rosebud O Roberts2, Bradley F Boeve2, David T Jones2, Ronald C Petersen2. 1. From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN. knopman@mayo.edu. 2. From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
Abstract
OBJECTIVE: To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. METHODS: Persons with AD dementia and elevated brain β-amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [(18)F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. RESULTS: The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. CONCLUSIONS: In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences.
OBJECTIVE: To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. METHODS: Persons with AD dementia and elevated brain β-amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [(18)F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. RESULTS: The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. CONCLUSIONS: In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences.
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