Motor Symptoms in Early- versus Late-Onset Alzheimer's Disease

Age at onset was suggested as one possible risk factor for motor dysfunction in Alzheimer's disease (AD).

We investigated the association of motor symptoms with cognition or neurodegeneration in patients with AD, and whether this association differs by the age at onset.

We included 113 amyloid positive AD patients and divided them into early-onset AD (EOAD) and late-onset AD (LOAD), who underwent the Unified Parkinson's Disease Rating Scale (UPDRS)-Part III (=UPDRS) scoring, Mini-Mental State Examination (MMSE)/Clinical Deterioration Rating Sum-of-Boxes (CDR-SOB), and magnetic resonance image (MRI). Multiple linear regression was used to evaluate the association of UPDRS and MMSE/CDR-SOB or MRI neurodegeneration measures, and whether the association differs according to the group.

The prevalence of motor symptoms and their severity did not differ between the groups. Lower MMSE (β= -1.1, p < 0.001) and higher CDR-SOB (β= 2.0, p < 0.001) were significantly associated with higher UPDRS. There was no interaction effect between MMSE/CDR-SOB and AD group on UPDRS. Global or all regional cortical thickness and putaminal volume were negatively associated with UPDRS score, but the interaction effect of neurodegeneration and AD group on UPDRS score was significant only in parietal lobe (p for interaction = 0.035), which showed EOAD to have a more pronounced association between parietal thinning and motor symptoms.

Our study suggested that the severity of motor deterioration in AD is related to the severity of cognitive impairment itself rather than age at onset, and motor symptoms might occur through multiple mechanisms including cortical and subcortical atrophy.