Highlights
- Neuropsychiatric symptoms, even in the absence of cognitive impairment, are linked to deteriorated daily functioning in older adults.
- Decreased motivation and emotional dysregulation are the strongest predictors of difficulties in daily activities.
- Apathy and depression further affect the ability to initiate and perform complex daily tasks.
- Partner-reported assessments may be more sensitive in detecting functional decline related to behavioral symptoms.
Clinical Background and Disease Burden
The aging population faces a growing risk of neuropsychiatric symptoms, commonly seen as precursors or companions to neurodegenerative disorders such as Alzheimer’s disease. Traditionally, research and clinical attention have focused on individuals already displaying cognitive impairment. However, neuropsychiatric symptoms—including decreased motivation, apathy, depression, and emotional dysregulation—may precede cognitive decline and independently impair quality of life by reducing the capacity for independent daily functioning. These symptoms can be subtle and easily overlooked in cognitively unimpaired older adults, contributing to significant unmet needs in early identification and intervention.
Research Methodology
A cross-sectional study presented by Mark A. Dubbelman, PhD, at the Alzheimer’s Association International Conference, examined 178 older adults (mean age 70.4 years, 62% female) without cognitive impairment. Importantly, 67% of participants reported no history of depression or psychiatric disorder. The study also included a well-acquainted study partner for each participant to provide collateral information.
Inclusion criteria allowed individuals with stable, non-current anxiety or depression, provided their medication regimen was infrequent and stable. Neuropsychiatric symptoms were measured using the Mild Behavioral Impairment Checklist (MBI-C), with both self-reported and partner-reported versions. The MBI-C evaluates five domains: motivation, emotional regulation, impulse control, social graces, and abnormal perceptions or thoughts.
Daily functioning was assessed using the Activities of Daily Living Prevention Instrument (ADCS-ADL-PI), with higher scores representing better function. Data were analyzed to determine associations between MBI-C and ADCS-ADL-PI scores, adjusting for age, sex, and education, and examined from both self and partner perspectives.
Key Findings
Of the cohort, 21 participants (12%) met criteria for mild behavioral impairment despite preserved cognition. Analyses revealed that higher levels of neuropsychiatric symptoms were significantly associated with lower daily functioning:
- Self-reported MBI-C scores were negatively correlated with daily functioning (B = –0.2; 95% CI, –0.35 to –0.05).
- Partner-reported MBI-C scores showed a similar but slightly weaker association (B = –0.15; 95% CI, –0.28 to –0.02).
- The relationship persisted when considering cross-reporting (partner to self: B = –0.51; 95% CI, –0.68 to –0.34; partner to partner: B = –0.5; 95% CI, –0.66 to –0.34).
Subdomain analysis identified decreased motivation and emotional dysregulation as the most robust predictors of impaired daily function. Specifically, decreased motivation was the most reliable self-reported predictor, while apathy (regardless of who reported it) consistently correlated with functional deficits. The study also found that difficulties with initiation—common in apathy, depression, and motivational decline—disproportionately affected the execution of more complex daily tasks (instrumental activities of daily living).
Mechanistic Insights
The link between neuropsychiatric symptoms and functional impairment is biologically plausible. Motivation and emotional regulation are mediated by frontostriatal and limbic networks, which can be affected by aging, subclinical neurodegeneration, or vascular changes even before overt cognitive symptoms arise. These circuits underpin not only mood and motivation but also executive functions necessary for planning and executing daily tasks. As such, behavioral symptoms may herald early neurobiological changes that precede cognitive decline and functional loss.
Expert Commentary
Dr. Dubbelman emphasized the clinical importance of these findings: “Symptoms like decreased motivation, depression and apathy can negatively impact a person’s ability to function independently in daily life. But so far, only a few studies have investigated this relationship, and most have focused on cognitively impaired individuals.” This study highlights the need for clinicians to assess behavioral symptoms in older adults regardless of cognitive status.
Limitations and Controversies
Several limitations merit consideration. The cross-sectional design precludes causal inferences; longitudinal studies are required to determine whether neuropsychiatric symptoms predict subsequent cognitive or functional decline. The reliance on self- and partner-reporting introduces potential bias; however, the inclusion of both perspectives strengthens the findings. The cohort was relatively small and may not fully represent the broader aging population, particularly across diverse cultural and educational backgrounds. Furthermore, the study did not control for subsyndromal psychiatric symptoms or the effects of stable medication use in all cases.
Conclusion
This study provides compelling evidence that neuropsychiatric symptoms—particularly decreased motivation and emotional dysregulation—are significant determinants of daily functioning in cognitively unimpaired older adults. Early identification and management of these symptoms could play a critical role in preserving independence and quality of life, and may offer a window for preventive interventions before the onset of cognitive decline. Future research should explore longitudinal outcomes and evaluate targeted behavioral or pharmacological interventions in this population.
References
1. Dubbelman MA, et al. Impact of neuropsychiatric symptoms on measures of daily functioning in older adults. Presented at: Alzheimer’s Association International Conference; July 27-31, 2025; Toronto.
2. Ismail Z, et al. The Mild Behavioral Impairment Checklist: A Screening Tool for Neuropsychiatric Symptoms in Pre-dementia Populations. J Alzheimers Dis. 2017;56(3):929-938.
3. Geda YE, et al. Neuropsychiatric symptoms in mild cognitive impairment and dementia: The Mayo Clinic Study of Aging. J Am Geriatr Soc. 2008;56(11):1985-1993.
