Baseline neuropsychiatric symptoms and psychotropic medication use midway through data collection of the Longitudinal Early‐ Onset Alzheimer’s Disease Study (LEADS) Cohort
Authors: Polsinelli Angelina J , Wonderlin Ryan J , Hammers Dustin B. , Garcia Alex Pena , Eloyan Ani , Taurone Alexander , Thangarajah Maryanne , Beckett Laurel , Gao Sujuan , Wang Sophia , Kirby Kala , Logan Paige E. , Aisen Paul S. S , Dage Jeff L. , Foroud Tatiana M. , Griffin Percy , Iaccarino Leo , Kramer Joel H. , Koeppe Robert A. , Kukull Walter A. , La Joie Renaud , Mundada Nidhi S , Murray Melissa E. , Nudelman Kelly N. H. , Soleimani‐Meigooni David N. , Rumbaugh Malia C. , Toga Arthur W. , Touroutoglou Alexandra , Vemuri Prashanthi , Atri Alireza , Day Gregory S. , Duara Ranjan , Graff‐Radford Neill R , Honig Lawrence S. , Jones David T. , Masdeu Joseph C. , Mendez Mario F. , Musiek Erik S. , Onyike Chiadi , Riddle Meghan C. , Rogalski Emily J , Salloway Stephen , Sha Sharon , Turner Raymond Scott , Wingo Thomas S. , Wolk David , Womack Kyle B. , Carrillo Maria C. , Dickerson Brad C. , Rabinovici Gil D. , Apostolova Liana G. 
Published: December 2023

Background

We examined neuropsychiatric symptoms (NPS) and psychotropic medication use at the midway point of data collection of the Longitudinal Early‐onset Alzheimer’s Disease Study (LEADS). We compared amyloid‐positive early‐onset Alzheimer’s disease (EOAD) participants and amyloid‐negative early‐onset non‐Alzheimer’s disease [EOnonAD]) participants across NPS domains and psychotropic medication categories.

Method

282 participants enrolled in LEADS were compared across diagnostic groups – amyloid‐positive EOAD (n = 212) and amyloid‐negative EOnonAD (n = 70). All participants were between ages 40 and 64 at baseline. NPS were measured with the Neuropsychiatric Inventory – Questionnaire (NPI‐Q) and Geriatric Depression Scale – Short Form (GDS‐SF). Medications were categorized into psychotropic category (e.g., antidepressants, antipsychotics, benzodiazepines). Groups were compared on NPI‐Q using binary logistic regression adjusting for sex and disease severity, on GDS‐SF using linear regression adjusting for sex and disease severity, and on psychotropic medication use using Chi square or Fisher’s exact test.

Result

Demographic data are presented in Table 1. Average total NPI‐Q score was higher in EOnonAD than EOAD (p = .002, ŋp
2 = .03). Regardless of diagnostic group, informants endorsed Affective behaviors most frequently (76.2%). EOAD informants endorsed fewer Distress‐Tension behaviors (p = .02, OR = .498) and Impulse Control behaviors (p = .01, OR = .438). EOAD informants also endorsed apathy (p < .001, OR = .316), irritability (p = .02, OR = .498), and disinhibition (p = .04, OR = .476) at lower frequency than EOnonAD. GDS‐SF showed that the EOnonAD participants self‐reported more symptoms of depression than the EOAD group (p = .002, ŋp
2 = .03). (Table 2A). A minority of participants, regardless of diagnostic group, reported psychotropic medication use (35%). There was higher use in EOnonAD (38%) than EOAD (24%) (p = .03, Cohen W = .14) (Table 2B).

Conclusion

NPS burden and psychotropic medication use were higher in EOnonAD than EOAD participants, despite EOnonAD being less severely impaired. LEADS continues to collect data. Future studies will examine etiologies that may be larger drivers of NPS than AD neuropathology, mediators (e.g., race, ethnicity) in the association between NPS and diagnostic group classication, compare NPS in EOAD vs. LOAD, and examine longitudinal changes in neuropsychiatric profiles.