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Original Investigation |

Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease A Retrospective Cohort Study

Daniel C. Aguirre-Acevedo, PhD1,2; Francisco Lopera, MD1; Eliana Henao, MS1; Victoria Tirado, MS1; Claudia Muñoz, MS1; Margarita Giraldo, MD1; Shrikant I. Bangdiwala, PhD3; Eric M. Reiman, MD4; Pierre N. Tariot, MD4; Jessica B. Langbaum, PhD4; Yakeel T. Quiroz, PhD1,5; Fabian Jaimes, PhD2,6
[+] Author Affiliations
1Neuroscience Group of Antioquia, University of Antioquia, Medellín, Colombia
2Academic Group of Clinical Epidemiology, University of Antioquia, Medellín, Colombia
3Department of Biostatistics, University of North Carolina at Chapel Hill
4Banner Alzheimer’s Institute, Phoenix, Arizona
5Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston
6Research Unit, Hospital Pablo Tobón Uribe, Medellín, Colombia
JAMA Neurol. 2016;73(4):431-438. doi:10.1001/jamaneurol.2015.4851.
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Importance  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.

Objectives  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.

Design, Setting, and Participants  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.

Main Outcomes and Measures  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 and Relevance  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.

Figures in this Article


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Figure 1.
Spaghetti Plot for Longitudinal Assessment of the Consortium to Establish a Registry for Alzheimer Disease Total Score (CERADts) in PSEN1 E280A Mutation Carriers
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Figure 2.
Model for Preclinical and Clinical Stage in PSEN1 E280A Mutation Carriers

CSF indicates cerebrospinal fluid; MCI, mild cognitive impairment; and PET, positron emission tomography.

Graphic Jump Location




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