Apolipoprotein E and Clusterin can magnify effects of personality vulnerability on declarative memory performance in non‐demented older adults

Abstract

Objectives Recent research has linked psychological (personality) factors and specific genetic risk polymorphisms to performance on neurocognitive phenotypes. We examined whether episodic or semantic memory performance is associated with (a) three personality traits (i.e., neuroticism, extraversion, openness to experience), (b) two neurodegenerative-related polymorphisms (i.e., Apolipoprotein E (APOE; rs7412; rs429358), Clusterin (CLU; rs11136000)), and (c) cross-domain risk interactions (magnification effects). Methods Linear growth models were examined to test independent associations between personality traits and declarative memory performance, and potential interaction effects with APOE and CLU genetic risk. Normal older adults (n = 282) with personality and genetic data from the Victoria Longitudinal Study were included at baseline and for up to 14 years of follow-up. Results First, we observed that higher openness to experience levels were associated with better episodic and semantic memory. Second, three significant gene × personality interactions were associated with poorer memory performance at baseline. These synergistic effects are: (a) APOE allelic risk (ε4+) carriers with lower openness to experience levels, (b) CLU (no risk: T/T) homozygotes with higher extraversion levels, and (c) CLU (no risk: T/T) homozygotes with lower neuroticism levels. Conclusions Specific neurodegenerative-related genetic polymorphisms (i.e., APOE and CLU) moderate and magnify the risk contributed by selected personality trait levels (i.e., openness to experience, extraversion) on declarative memory performance in non-demented aging. Future research could target interactions of other personality traits and genetic polymorphisms in different clinical populations for predicting other neurocognitive deficits or transitions to cognitive impairment and dementia.

A Network of Genetic Effects on Non-Demented Cognitive Aging: Alzheimer’s Genetic Risk (CLU + CR1 + PICALM) Intensifies Cognitive Aging Genetic Risk (COMT + BDNF) Selectively for APOE ɛ4 Carriers

“…In healthy young adults, CLU allelic risk had lower white matter integrity than their counterparts [33] which may indicate an increased risk for developing dementia in old age. CLU is also similar in structure with the molten globule structure of APOE and they may influence each other in frontal lobe regions [10,34,35]. …”

Apolipoprotein E genotype does not moderate the associations of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive aging in the Lothian Birth Cohort 1936

“…Results from other studies on the APOE -by-neuroticism interaction suggest that the specific cognitive domains studied should also be considered. Sapkota et al found the APOE -by-neuroticism interaction did not predict baseline or subsequent change in declarative memory [ 24 ]. Chapman et al found an overall APOE -by-neuroticism interaction in a multivariate analysis of variance with five cognitive domains as outcomes [ 27 ].…”

“…Only one of three studies that used multiple, more challenging cognitive tests to measure cognition reported that depressive symptoms were more strongly related to cognition in E4 carriers ([ 21 ], cf. [ 22 – 24 ]). Regarding neuroticism, in the Ginkgo Evaluation of Memory sample neuroticism has a greater negative association with cognitive ability [ 25 ] and subsequent cognitive decline [ 26 ] in E4 carriers.…”

“…Regarding neuroticism, in the Ginkgo Evaluation of Memory sample neuroticism has a greater negative association with cognitive ability [ 25 ] and subsequent cognitive decline [ 26 ] in E4 carriers. In the Victoria Longitudinal Study sample, however, APOE E4 status did not moderate the relationships of neuroticism with baseline declarative memory and subsequent decline in declarative memory [ 24 ]. Furthermore, a cross-sectional study of 172 non-demented older adults based in Rochester, New York, USA, found that there was overall APOE -by-neuroticism interaction when predicting scores on five cognitive domains, although the only specific domain for which the interaction was statistically significant was attention [ 27 ].…”

Normal Aging and Dementia

“…Moreover, increased plasma apoJ levels in MCI indicated an amplified risk of further cognitive decline. Furthermore, it was shown that genetic variation in the CLU region may amplify the influence of personality type on the performance of declarative memory in older, non-demented adults [71].…”