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Predictive biomarkers of individual trajectories in elderly persons with subtle cognitive decline: APOE genotype data

Citation

Herrmann, Francois; Giannakopoulos, Panteleimon (2020), Predictive biomarkers of individual trajectories in elderly persons with subtle cognitive decline: APOE genotype data, Dryad, Dataset, https://doi.org/10.5061/dryad.3tx95x6dp

Abstract

The mentalizing network (MN) treats social interactions based on our understanding of other people’s intentions and includes the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ), posterior cingulate cortex (PCC), precuneus (PC) and amygdala. Not all elders are equally affected by the aging-related decrease of mentalizing abilities. Personality has recently emerged as a strong determinant of functional connectivity in MN areas. However, its impact on volumetric changes across the mentalizing network in brain aging is still unknown. To address this issue, we explored the determinants of volume decrease in MN components including amyloid burden, personality, and APOE genotyping in a previously established cohort of 130 healthy elders with a mean follow-up of 54 months. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models corrected for multiple comparisons were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele and cognitive evolution. In cases with higher Agreeableness scores, there were lower volume losses in posterior cingulate cortex (PCC), precuneus (PC) and amygdala bilaterally. This was also the case for right medial prefrontal cortex (mPFC) in elders displaying lower Agreeableness and Conscientiousness. In multiple regression models, the effect of Agreeableness was still observed in left PC and right amygdala and that of Conscientiousness in right mPFC volume loss (26.3% of variability, significant age, sex). Several Agreeableness (Modesty) and Conscientiousness (order, dutifulness, achievement striving and self-discipline) facets were positively related to increased volume loss in cortical components of the MN. In conclusion, these data challenge the beneficial role of higher levels of Agreeableness and Conscientiousness in old age showing that they are associated with an increased rate of volume loss within the mentalizing network.

Usage Notes

We report here the data from a longitudinal analysis exploring the determinants of volume decrease in mentalizing network components including amyloid burden, personality, and APOE genotyping in a previously established cohort of 130 healthy elders with a mean follow-up of 54 months.

All of the cases were recruited via advertisements in local newspapers and media. Exclusion criteria included psychiatric or neurologic disorders, sustained head injury, history of major medical disorders (neoplasm or cardiac illness), alcohol or drug abuse, regular use of neuroleptics, antidepressants or psychostimulants and contraindications to PET or MRI scans. To control for the confounding effect of vascular pathology on MRI findings, individuals with subtle cardiovascular symptoms, hypertension (non treated) and a history of stroke or transient ischemic episodes were also excluded from the present study. The initial cohort included 526 elderly white non-Latinos of mixed European descent individuals living in Geneva and Lausanne catchment area. Due to the need for an excellent French knowledge (in order to participate in detailed neuropsychological testing) the vast majority of the participants were Swiss (or born in French-speaking European countries, 92%).

Cases with three neurocognitive assessments at baseline, 18 months and 54 months, structural brain MRI at baseline and 54-months post-inclusion, brain amyloid PET at follow-up and APOE status were considered. The sample 54-months post-inclusion included 397 cases. As a sub-project of this cohort study, the NEO-PI-R assessment was administrated randomly at inclusion in 130 elderly controls.

Whole blood samples were collected at baseline for all subjects for APOE genotyping. Standard DNA extraction was performed using either 9 ml EDTA tubes (Sarstedt, Germany) or Oragene Saliva DNA Kit (DNA Genotek, Inc., Ottawa, ON, Canada) which were stored at -20°C. APOE genotyping was done on the LightCycler (Roche Diagnostics, Basel, Switzerland) as described previously . Subjects were divided according to their APOE epsilon 4 allele status (4/3 versus 3/3, 3/2 carriers).

Funding

National Science Foundation, Award: 320030-169390