Co-occurrence of neuropsychiatric symptoms in ADAMS, ADNI and NACC studies as assessed by Neuropsychiatric Inventory
Authors: Galankin Timofey L. , Swartz Jina , Moebius Hans J. , Bespalov Anton Y. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

Objective

Neuropsychiatric symptoms (NPS) are very common and associated with high levels of distress, both in dementia patients and their caregivers. Especially at more advanced dementia disease stages, NPS rarely occur in isolation, and the presence of two or more NPS may affect disease severity as well as the response to therapy. There is limited quantitative information on prevalence of specific symptom combinations in the general population, as well as in the populations recruited for symptom-specific investigations.

Methods

We performed cross-sectional analyses of publicly accessible Neuropsychiatric Inventory and Mini Mental State Examination (MMSE) data from three longitudinal studies (Aging, Demographics, and Memory Study (ADAMS), Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the National Alzheimer’s Coordinating Center data (NACC)). Mean (with 95% confidence interval) prevalence was calculated for all possible pairs of symptoms (aberrant motor behavior, agitation/aggression, anxiety, apathy/indifference, appetite/eating changes, delusions; depression/dysphoria; disinhibition; elation/euphoria; hallucinations; irritability/lability and nighttime behavioral disturbances) in different MMSE strata. In addition, the conditional prevalence of one symptom given another symptom was provided for all possible combinations.

Results

In all three studies and MMSE strata, we observed every possible pair combination, from commonly recognized and discussed associations (e.g., hallucinations and delusions) to what might be seen as rather counter-intuitive patterns (e.g., apathy and agitation). Prevalence of symptom pairs cannot be readily predicted based on prevalence of individual symptoms. Presence of cognitive deficit and degree of cognitive impairment affected prevalence of all symptoms and symptom pairs, albeit to a different degree. For example, prevalence of the most common symptom, depression, in subjects without and with cognitive deficit, differed less than two-fold. In contrast, differences in the prevalence of psychotic symptoms (hallucinations and/or delusions) in subjects with and without cognitive deficit were much stronger (6- to 38-fold).

Conclusions

The present study illustrates that, while there is the possibility of any combination of neuropsychiatric symptoms presenting during the course of dementia, their co-occurrence cannot be readily predicted based on the prevalence of individual symptoms. Thus, our study results can serve as a source of reference information to inform the design and recruitment strategies for future clinical studies and epidemiological research on neuropsychiatric symptoms in people with dementia.

Highlights

What is the primary question addressed by this study?—The question addressed by the study must limited to only one sentence.

There is very limited quantitative information on prevalence of neuropsychiatric symptom combinations despite the growing number of epidemiological and drug development studies in the field.

What is the main finding of this study?—The finding must be limited to two sentences.

All possible pair combinations frequently occur even in subjects with mild, minimal or no cognitive deficit in the general population, as well as in protocol-based dementia research studies.

Co-occurrence of neuropsychiatric symptoms cannot be readily predicted based on the prevalence of individual symptoms.

What is the meaning of the finding?—The meaning of the finding must be limited to one sentence.

We provide reference information on neuropsychiatric symptom pair prevalence to inform the design and recruitment strategies for future clinical studies, as well as epidemiological research on neuropsychiatric symptoms.