Impact of motor dysfunction on neuropsychiatric symptom profile in patients with autopsy-confirmed Alzheimer’s disease

Motor dysfunction, which includes changes in gait, balance, and/or functional mobility, is a lesser-known feature of Alzheimer’s Disease (AD), especially as it relates to the development of neuropsychiatric symptoms (NPS). This study (1) compared rates of NPS between autopsy-confirmed AD patients with and without early-onset motor dysfunction and (2) compared rates of non-AD dementia autopsy pathology (Lewy Body disease, Frontotemporal Lobar degeneration) between these groups. This retrospective longitudinal cohort study utilized National Alzheimer’s Coordinating Center (NACC) data. Participants (N = 856) were required to have moderate-to-severe autopsy-confirmed AD, Clinical Dementia Rating-Global scores of ≤1 at their index visit, and NPS and clinician-rated motor data. Early motor dysfunction was associated with significantly higher NPI-Q total scores (T = 4.48, p <.001) and higher odds of delusions (OR [95%CI]: 1.73 [1.02–2.96]), hallucinations (2.45 [1.35–4.56]), depression (1.51 [1.11–2.06]), irritability (1.50 [1.09–2.08]), apathy (1.70 [1.24–2.36]), anxiety (1.38 [1.01–1.90]), nighttime behaviors (1.98 [1.40–2.81]), and appetite/eating problems (1.56 [1.09–2.25]). Early motor dysfunction was also associated with higher Lewy Body disease pathology (1.41 [1.03–1.93]), but not Frontotemporal Lobar degeneration (1.10 [0.71–1.69]), on autopsy. Our results suggest that motor symptoms in early AD are associated with a higher number and severity of NPS, which may be partially explained by comorbid non-AD neuropathology.