title: Effect of intellectual enrichment on AD biomarker trajectories: Longitudinal imaging study.
abstract: OBJECTIVE
  To investigate the effect of age, sex, APOE4 genotype, and lifestyle enrichment (education/occupation, midlife cognitive activity, and midlife physical activity) on Alzheimer disease (AD) biomarker trajectories using longitudinal imaging data (brain β-amyloid load via Pittsburgh compound B PET and neurodegeneration via (18)fluorodeoxyglucose (FDG) PET and structural MRI) in an elderly population without dementia.
  
  
  METHODS
  In the population-based longitudinal Mayo Clinic Study of Aging, we studied 393 participants without dementia (340 clinically normal, 53 mild cognitive impairment; 70 years and older) who had cognitive and physical activity measures and at least 2 visits with imaging biomarkers. We dichotomized participants into high (≥14 years) and low (<14 years) education levels using the median. For the entire cohort and the 2 education strata, we built linear mixed models to investigate the effect of the predictors on each of the biomarker outcomes.
  
  
  RESULTS
  Age was associated with amyloid and neurodegeneration trajectories; APOE4 status appears to influence only the amyloid and FDG trajectories but not hippocampal volume trajectory. In the high-education stratum, high midlife cognitive activity was associated with lower amyloid deposition in APOE4 carriers. APOE4 status was associated with lower FDG uptake in the entire cohort and in participants with lower education but not the high-education cohort.
  
  
  CONCLUSIONS
  There were minimal effects of lifestyle enrichment on AD biomarker trajectories (specifically rates). Lifetime intellectual enrichment (high education, high midlife cognitive activity) is associated with lower amyloid in APOE4 carriers. High education is protective from the APOE4 effect on FDG metabolism. Differing education levels may explain the conflicting results seen in the literature.
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ. vemuri.prashanthi@mayo.edu.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Przybelski
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Mary
authors.initials: M
authors.lastname: Machulda
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Yonas E
authors.initials: YE
authors.lastname: Geda
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Rocca
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: From the Departments of Radiology (P.V., V.J.L., J.L.G., M.L.S., C.R.J.), Health Sciences Research (T.G.L., S.A.P., M.M.M., R.O.R., W.A.R.), Neurology (D.S.K., M.M.M., R.O.R., W.A.R., R.C.P.), and Psychology (M.M., Y.E.G.), Mayo Clinic, Rochester, MN; and Departments of Psychiatry (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D015331:Cohort Studies; D004522:Educational Status; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D009790:Occupations / Q000639:trends*; D011159:Population Surveillance / Q000379:methods; D040242:Risk Reduction Behavior; D011795:Surveys and Questionnaires
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers