title: Self-reported memory complaints: implications from a longitudinal cohort with autopsies.
abstract: OBJECTIVE
  We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.
  
  
  METHODS
  Subjects (n = 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n = 243).
  
  
  RESULTS
  SMCs were reported by more than half (55.7%) of the cohort, and were associated with increased risk of impairment (unadjusted odds ratio = 2.8, p < 0.0001). Mild cognitive impairment (dementia) occurred 9.2 (12.1) years after SMC. Multistate modeling showed that SMC reporters with an APOE ε4 allele had double the odds of impairment (adjusted odds ratio = 2.2, p = 0.036). SMC smokers took less time to transition to mild cognitive impairment, while SMC hormone-replaced women took longer to transition directly to dementia. Among participants (n = 176) who died without a diagnosed clinical impairment, SMCs were associated with elevated neuritic amyloid plaques in the neocortex and medial temporal lobe.
  
  
  CONCLUSIONS
  SMC reporters are at a higher risk of future cognitive impairment and have higher levels of Alzheimer-type brain pathology even when impairment does not occur. As potential harbingers of future cognitive decline, physicians should query and monitor SMCs from their older patients.
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY. kryscio@email.uky.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Cooper
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Smith
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wan
authors.affiliation: From the Sanders-Brown Center on Aging (R.J.K., E.L.A., G.E.C., G.A.J., P.T.N., C.D.S., L.J.V.E., L.W., F.A.S.), Alzheimer's Disease Center (R.J.K., E.L.A., G.E.C., D.W.F., G.A.J., P.T.N., C.D.S., L.J.V.E., F.A.S.), Departments of Biostatistics (R.J.K., D.W.F.), Statistics (R.J.K., L.W.), Epidemiology (E.L.A.), and Pathology (P.T.N.), Department of Anatomy and Neurobiology, College of Medicine (L.J.V.E.), and Department of Neurology, College of Medicine (G.A.J., C.D.S., F.A.S.), University of Kentucky, Lexington; and Baptist Neurology Center (G.E.C.), Lexington, KY.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
mesh_terms: D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000523:psychology*; D053329:Apolipoprotein E2 / Q000235:genetics; D060825:Cognitive Dysfunction / Q000150:complications / Q000453:epidemiology* / Q000523:psychology; D003704:Dementia / Q000150:complications / Q000453:epidemiology* / Q000523:psychology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007629:Kentucky / Q000453:epidemiology; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D019579:Neocortex / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D012307:Risk Factors; D057566:Self Report; D013702:Temporal Lobe / Q000378:metabolism
chemical_list: D053329:Apolipoprotein E2