Can Addressing Personality Change Enhance Cognitive Functioning and Delay Development of Mild Cognitive Impairment?

It is well established that certain personality traits predict the likelihood of cognitive decline. High neuroticism (i.e., the tendency to experience anxiety and other negative emotions) in older adults has been repeatedly associated with subsequent cognitive decline and an increased likelihood of developing mild cognitive impairment (MCI) and Alzheimer’s disease (AD)^{1, 2}. The vast majority of these studies have used neuroticism collected at baseline as a predictor of subsequent cognitive change.

In this issue of the Journal of the American Geriatrics Society, Caselli et al. extend this literature with evidence that longitudinal changes in personality precede the transition to MCI in cognitively normal older adults ³. Specifically, neuroticism increased and openness to experience decreased over seven years in older adults who later transitioned to MCI. Moreover, these “trait” personality changes coincided with increased “state” anxiety, depression, and irritability, as well as decreased executive functioning and memory. Caselli and colleagues present a compelling argument that subtle changes in personality traits may coincide with or follow cognitive decline, and they precede the onset of more clinically significant state behavioral disturbances (e.g., depression). The authors conclude that a potential novel treatment target for state behavioral disorders in MCI and AD would be the early detection and intervention of maladaptive personality traits. We are enthusiastic about this possibility, and speculate that the targeting of personality and behavioral disturbances may also delay onset of cognitive impairment in some older adults.

Recent evidence suggests interventions targeting personality and behavioral disturbances are successful in ameliorating these behaviors and improving cognition. Mindfulness meditation involves exercising focused attention and practicing emotional regulation through nonjudgmental awareness of thoughts and physical sensations one experiences. In a recent randomized controlled trial of 103 older adults with anxiety and depressive disorders, training in mindfulness meditation resulted in greater improvement in memory, generalized worry, and depression when compared with a health-education control condition⁴. Mindfulness meditation training also decreased neuroticism measured with the NEO-PI-R (the same measure of personality used by Caselli et al.) over 15 months in a sample of 138 adults who previously met criteria for major depression and had an average age of 50 years⁵.

Computerized cognitive training (CCT) is another behavioral intervention, one that uses repetitive learning to improve cognition or socio-emotional functioning and presumably change underlying brain functioning⁶. Randomized controlled trials using cognitively normal and psychiatrically healthy older adults reveal CCT stabilizes cognitive functioning in processing speed and reasoning over 10 years⁷. In older adults with major depression, Anguera et al.⁸ found that 20+ hours of CCT improved depressive symptoms, executive functioning, and decreased negative responding on an emotional categorization task, a proxy of neuroticism. Thus, by reducing known risk factors for cognitive decline (i.e., depression, neuroticism) mindfulness meditation and cognitive training may delay the onset of MCI. This hypothesis remains to be tested in groups of patients believed to have prodromal Alzheimer’s disease.

Clarifying the neurobiology of personality and behavioral disturbances would help guide novel treatment approaches. Caselli et al. speculate that a decline in frontally-mediated executive functioning contributes to later changes in personality and behavior. This is an appealing hypothesis, and it is supported by findings that high neuroticism in 45 middle aged adults is associated with decreased resting state functional connectivity between cognitive-executive control regions (e.g., dorsolateral prefrontal cortex) and emotional processing centers of the insula and amygdala⁹. Clearly, dysfunction of the amygdala is critical to the occurrence of neuroticism¹⁰ and anxiety¹¹, depression¹², and irritability¹³, the same state behaviors observed to coincide with personality trait change by Caselli et al. While neurofibrillary tangle deposition does not begin in the amygdala, the amygdala is susceptible to tangle deposits relatively early in the AD process¹⁴, and other signs of neurodegeneration quickly accumulate in large amounts here^{15, 16}. Thus, subtle trait/state changes, together with neuronal dysfunction in the amygdala and hippocampus¹⁷, may represent an early harbinger of cognitive decline.

Findings from Caselli et al are important starting points for drawing hypotheses about the connection between behavior and pathology in the early AD process. Whereas further work is needed to disentangle “trait” and “state” manifestations of limbic dysfunction in older adults¹⁸, there are important clinical implications here. Brief self-reported assessments of neuroticism and depression could be routinely provided to older patients in the waiting rooms of primary care offices or administered by nursing staff as part of a clinical encounter. Elevations in neuroticism and /or depression would help alert clinicians to older adults at risk for potential cognitive decline, and potentially a wide range of other age-related detrimental health outcomes, e.g., Fried’s frailty phenotype¹⁹. Importantly, increasing evidence suggests these behaviors may be modifiable. Whereas mindfulness meditation and CCT are not routinely offered as part of primary care services, meditation practices and retreats can be found within many communities, and the same CCT programs used in some of the research studies mentioned above⁷ are commercially available. Future research is needed to monitor cognitive outcomes in intervention studies of trait and state emotion dysregulation over time.