DOI: 10.5061/dryad.3tx95x6dp
title: Predictive biomarkers of individual trajectories in elderly persons with subtle cognitive decline: APOE genotype data

description: 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.
description: 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).