title: Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia: a population-based study.
abstract: OBJECTIVE
  To investigate the population-based interaction between a biological variable (APOE ε4), neuropsychiatric symptoms, and the risk of incident dementia among subjects with prevalent mild cognitive impairment (MCI).
  
  
  METHODS
  We prospectively followed 332 participants with prevalent MCI (aged 70 years and older) enrolled in the Mayo Clinic Study of Aging for a median of 3 years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria, after reviewing neurologic, cognitive, and other pertinent data. Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Questionnaire. We used Cox proportional hazards models, with age as a time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were adjusted for sex, education, and medical comorbidity.
  
  
  RESULTS
  Baseline agitation, nighttime behaviors, depression, and apathy significantly increased the risk of incident dementia. We observed additive interactions between APOE ε4 and depression (joint effect HR = 2.21; 95% CI = 1.24-3.91; test for additive interaction, p < 0.001); and between APOE ε4 and apathy (joint effect HR = 1.93; 95% CI = 0.93-3.98; test for additive interaction, p = 0.031). Anxiety, irritability, and appetite/eating were not associated with increased risk of incident dementia.
  
  
  CONCLUSIONS
  Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression, and apathy elevated the risk of incident dementia. There was a synergistic interaction between depression or apathy and APOE ε4 in further elevating the risk of incident dementia.
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Anna
authors: A
authors: Pink
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Gorazd B
authors: GB
authors: Stokin
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Mairead M
authors: MM
authors: Bartley
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Rosebud O
authors: RO
authors: Roberts
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Ondrej
authors: O
authors: Sochor
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Mary M
authors: MM
authors: Machulda
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Janina
authors: J
authors: Krell-Roesch
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: David S
authors: DS
authors: Knopman
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Jazmin I
authors: JI
authors: Acosta
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Teresa J
authors: TJ
authors: Christianson
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: V Shane
authors: VS
authors: Pankratz
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Michelle M
authors: MM
authors: Mielke
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
authors: Ronald C
authors: RC
authors: Petersen
authors: From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria. geda.yonas@mayo.edu.
authors: Yonas E
authors: YE
authors: Geda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D009483:Neuropsychological Tests; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4
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