title: Multiple pathologies are common and related to dementia in the oldest-old: The 90+ Study.
abstract: OBJECTIVE
  The purpose of this study was to examine the role of multiple pathologies in the expression of dementia in the oldest-old.
  
  
  METHODS
  A total of 183 participants of The 90+ Study with longitudinal follow-up and autopsy were included in this clinical-pathologic investigation. Eight pathologic diagnoses (Alzheimer disease [AD], microinfarcts, hippocampal sclerosis, macroinfarcts, Lewy body disease, cerebral amyloid angiopathy, white matter disease, and others) were dichotomized. We estimated the odds of dementia in relation to each individual pathologic diagnosis and to the total number of diagnoses. We also examined dementia severity in relation to number of pathologic diagnoses.
  
  
  RESULTS
  The presence of multiple pathologic diagnoses was common and occurred more frequently in those with dementia compared with those without dementia (45% vs 14%). Higher numbers of pathologic diagnoses were also associated with greater dementia severity. Participants with intermediate/high AD pathology alone were 3 times more likely to have dementia (odds ratio = 3.5), but those with single non-AD pathologies were 12 times more likely to have dementia (odds ratio = 12.4). When a second pathology was present, the likelihood of dementia increased 4-fold in those with intermediate/high AD pathology but did not change in those with non-AD pathologies, suggesting that pathologies may interrelate in different ways.
  
  
  CONCLUSIONS
  In the oldest-old, the presence of multiple pathologies is associated with increased likelihood and severity of dementia. The effect of the individual pathologies may be additive or perhaps synergistic and requires further research. Multiple pathologies will need to be targeted to reduce the burden of dementia in the population.
authors.affiliation: From the Departments of Neurology (C.H.K., S.S.B., M.M.C.), Neurobiology & Behavior (C.H.K.), and Epidemiology (C.H.K., M.M.C.), Institute for Memory Impairments and Neurological Disorders (C.H.K., M.M.C.), and School of Biological Sciences (T.T.), University of California, Irvine; Department of Pathology (R.K.), University of California, Irvine Medical Center, Orange, CA; Department of Pathology (J.S.), Huntsman Cancer Institute, University of Utah, Salt Lake City. ckawas@uci.edu.
authors.forename: Claudia H
authors.initials: CH
authors.lastname: Kawas
authors.affiliation: From the Departments of Neurology (C.H.K., S.S.B., M.M.C.), Neurobiology & Behavior (C.H.K.), and Epidemiology (C.H.K., M.M.C.), Institute for Memory Impairments and Neurological Disorders (C.H.K., M.M.C.), and School of Biological Sciences (T.T.), University of California, Irvine; Department of Pathology (R.K.), University of California, Irvine Medical Center, Orange, CA; Department of Pathology (J.S.), Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Kim
authors.affiliation: From the Departments of Neurology (C.H.K., S.S.B., M.M.C.), Neurobiology & Behavior (C.H.K.), and Epidemiology (C.H.K., M.M.C.), Institute for Memory Impairments and Neurological Disorders (C.H.K., M.M.C.), and School of Biological Sciences (T.T.), University of California, Irvine; Department of Pathology (R.K.), University of California, Irvine Medical Center, Orange, CA; Department of Pathology (J.S.), Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sonnen
authors.affiliation: From the Departments of Neurology (C.H.K., S.S.B., M.M.C.), Neurobiology & Behavior (C.H.K.), and Epidemiology (C.H.K., M.M.C.), Institute for Memory Impairments and Neurological Disorders (C.H.K., M.M.C.), and School of Biological Sciences (T.T.), University of California, Irvine; Department of Pathology (R.K.), University of California, Irvine Medical Center, Orange, CA; Department of Pathology (J.S.), Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Szofia S
authors.initials: SS
authors.lastname: Bullain
authors.affiliation: From the Departments of Neurology (C.H.K., S.S.B., M.M.C.), Neurobiology & Behavior (C.H.K.), and Epidemiology (C.H.K., M.M.C.), Institute for Memory Impairments and Neurological Disorders (C.H.K., M.M.C.), and School of Biological Sciences (T.T.), University of California, Irvine; Department of Pathology (R.K.), University of California, Irvine Medical Center, Orange, CA; Department of Pathology (J.S.), Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Thomas
authors.initials: T
authors.lastname: Trieu
authors.affiliation: From the Departments of Neurology (C.H.K., S.S.B., M.M.C.), Neurobiology & Behavior (C.H.K.), and Epidemiology (C.H.K., M.M.C.), Institute for Memory Impairments and Neurological Disorders (C.H.K., M.M.C.), and School of Biological Sciences (T.T.), University of California, Irvine; Department of Pathology (R.K.), University of California, Irvine Medical Center, Orange, CA; Department of Pathology (J.S.), Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: María M
authors.initials: MM
authors.lastname: Corrada
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000145:classification* / Q000473:pathology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index