title: Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease: A Retrospective Cohort Study.
abstract: OBJECTIVE
  Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline.
  
  
  OBJECTIVE
  To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline.
  
  
  METHODS
  We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline.
  
  
  METHODS
  Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline.
  
  
  RESULTS
  A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word list recall test and 2.13 (95% CI, -2.29 to -1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (-2.89 vs -2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset.
  
  
  CONCLUSIONS
  Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment.
authors.affiliation: Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia2Academic Group of Clinical Epidemiology, University of Antioquia, Medellín, Colombia.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Aguirre-Acevedo
authors.affiliation: Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.affiliation: Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia.
authors.forename: Eliana
authors.initials: E
authors.lastname: Henao
authors.affiliation: Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia.
authors.forename: Victoria
authors.initials: V
authors.lastname: Tirado
authors.affiliation: Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia.
authors.forename: Margarita
authors.initials: M
authors.lastname: Giraldo
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill.
authors.forename: Shrikant I
authors.initials: SI
authors.lastname: Bangdiwala
authors.affiliation: Banner Alzheimer's Institute, Phoenix, Arizona.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: Banner Alzheimer's Institute, Phoenix, Arizona.
authors.forename: Pierre N
authors.initials: PN
authors.lastname: Tariot
authors.affiliation: Banner Alzheimer's Institute, Phoenix, Arizona.
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Langbaum
authors.affiliation: Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia5Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston.
authors.forename: Yakeel T
authors.initials: YT
authors.lastname: Quiroz
authors.affiliation: Academic Group of Clinical Epidemiology, University of Antioquia, Medellín, Colombia6Research Unit, Hospital Pablo Tobón Uribe, Medellín, Colombia.
authors.forename: Fabian
authors.initials: F
authors.lastname: Jaimes
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D003105:Colombia / Q000453:epidemiology; D005260:Female; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1