title: Neuropsychological function in nondemented carriers of presenilin-1 mutations.
abstract: BACKGROUND
  Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD).
  
  
  OBJECTIVE
  To investigate these observations by the study of persons at risk for autosomal dominant forms of AD.
  
  
  METHODS
  Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE epsilon4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs.
  
  
  RESULTS
  MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE epsilon4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores.
  
  
  CONCLUSIONS
  This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers. Depression, gender, and presence of an APOE epsilon4 allele did not demonstrate large influences on neuropsychological performance.
authors.affiliation: Alzheimer's Disease Center, University of California, Los Angeles, CA 90095-1769, USA. jringman@mednet.ucla.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Ringman
authors.forename: C
authors.initials: C
authors.lastname: Diaz-Olavarrieta
authors.forename: Y
authors.initials: Y
authors.lastname: Rodriguez
authors.forename: M
authors.initials: M
authors.lastname: Chavez
authors.forename: L
authors.initials: L
authors.lastname: Fairbanks
authors.forename: F
authors.initials: F
authors.lastname: Paz
authors.forename: A
authors.initials: A
authors.lastname: Varpetian
authors.forename: H C
authors.initials: HC
authors.lastname: Maldonado
authors.forename: M A
authors.initials: MA
authors.lastname: Macias-Islas
authors.forename: J
authors.initials: J
authors.lastname: Murrell
authors.forename: B
authors.initials: B
authors.lastname: Ghetti
authors.forename: C
authors.initials: C
authors.lastname: Kawas
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology*; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology*; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D042241:Early Diagnosis; D005192:Family Health; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008569:Memory Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D053764:Presenilin-1; D012737:Sex Factors
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1