Neuroticism and Guardedness May Herald Alzheimer Disease


New-onset neuroticism and guardedness may be incipient signs of Alzheimer Disease, according to a new study.



Personality and behavioral changes that characterize frank dementia emerge during the incipient stages of Alzheimer disease (AD), according to a report by researchers affiliated with the Mayo Clinic Arizona in Scottsdale.1 The findings may prove useful in designing preventive care strategies based on not only the current standard of focus on cognitive outcomes but on behavioral outcomes as well.

The team sought to determine whether personality changes that signal the emergence of vexing behavioral disorders that characterize AD arise during the transition from preclinical AD to mild cognitive impairment (MCI). The study population consisted of 277 subjects: each subject who was homozygous for apolipoprotein E (APOE) ɛ4 was matched with 1 subject who was heterozygous and 2 noncarriers. All participants were neuropsychiatrically healthy at study outset. Scores from serial administration of the Neuroticism, Extraversion, and Openness Personality Inventory- Revised (NEO-PI-R), meant to measure personality traits-not psychological pathology, were captured along with a battery of neuropsychological tests. All assessments were directly administered to the study participants rather than being based on informant recollection.

Twenty five subjects in whom MCI developed over 7 years from study initiation were compared with 252 nontransitioners. Demographic analysis showed that transitioners were much more likely to have the APOE ɛ4 gene than nontransitioners (80% vs 38/%; P < .001). Otherwise, no significant differences were seen between groups in regard to age, sex, ethnicity, education level, or baseline NEO-PI-R scores. The primary outcome was change in NEO-PI-R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from the time of study entry to MCI diagnosis or an equivalent duration in nontransitioners.

New Onset Neuroticism/Guardedness May Be Incipient Signs of AD

The researchers found a significant increase in NEO-PI-R neuroticism T-scores in MCI transitioners compared with nontransitioners (mean 2.9 vs 0; P = .02) and a significant decrease in openness in MCI transitioners compared with nontransitioners (mean −4.8 vs −1.0; P < .001). Neuroticism T-scores increased by more than 5 points in 40% of transitioners versus 18% of nontransitioners (P = .01). Openness T-score declined by more than 5 points in 48% of transitioners versus 21% of nontransitioners (P = .003).Statistically significant, but clinically insignificant differences in behavioral scores were also seen for measures of depression, somatization, irritability, anxiety, and aggressive attitude.

This was the first study to demonstrate that changes in personality, namely an increase in neuroticism and decrease in openness with concomitant subtle changes regarding somatization, depression, anxiety, irritability, and aggression, coincide with the transition from preclinical AD to MCI. They also noted that no differences in baseline personality or behavioral scores indicated a predisposition to negative changes in this study, such that the findings were consistent with their hypothesis that the changes seen were intrinsic to the disease process. They also stressed that behavioral symptoms of MCI and AD pose major therapeutic challenges, as use of psychiatric drugs runs high in this population but affords little benefit.2,3

The authors called for further study to correlate early-stage personality changes with behavioral outcomes in efforts to help ameliorate adverse outcomes. They added that early patient and caregiver disclosure about what to expect regarding impending behavioral risks will better equip them to make prospective medical and other life planning decisions and establish a base for participation in clinical trials and prevention strategies.


1.Caselli RJ, Langlais BT, Dueck AC, et al. Personality changes during the transition from cognitive health to mild cognitive impairment. J Am Geriatr Soc. 2018 Jan 17. [Epub ahead of print]

2. Schneider LS, Tariot PN, Dagerman KS, et al for CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. New Engl J Med. 2006;355(15):1525-1538.

3. Maust DT, Kim HM, Seyfried LS, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry 2015;72:438-445.

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