Padala, P. R., Boozer, E. M., Lensing, S. Y., Parkes, C. M., Hunter, C. R., Dennis, R. A., … & Padala, K. P. (2020). Neuromodulation for Apathy in Alzheimer’s Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study. Journal of Alzheimer’s Disease, (Preprint), 1-11.
Background: Apathy, a profound loss of motivation, initiation, and goal directed cognition, is a common comorbidity of Alzheimer’s disease (AD). The presence of apathy is associated with rapid progression of AD, long-term impairment, disability, and higher mortality. Pharmacological treatments of apathy are limited.
Objective: The primary objective was to evaluate the efﬁcacy of repetitive transcranial magnetic stimulation (rTMS) for apathy in AD.
Methods: A randomized, double-blind, parallel-arm, sham-controlled pilot study was conducted in subjects with AD and apathy (N=20). Subjects were randomized to rTMS or sham treatment (5days/week) for four weeks. Primary outcome, apathy evaluation scale-clinician version (AES-C), and secondary outcome measures, modiﬁed-Mini Mental State Examination (3MS), instrumental activities of daily living (IADL), and clinical global impression (CGI), were assessed at baseline and four weeks. Follow-up visits were conducted at 8 and 12 weeks to test the durability of effects of intervention.
Results: Mean age was 77.3 (±7.2) years, 80% were Caucasians and 10% were females. After adjusting for baseline, there was a signiﬁcantly greater improvement in the AES-C with rTMS compared to sham treatment (–10.1 (–15.9 to –4.3); t(16) =–3.69; p=0.002) at 4 weeks. There was also signiﬁcantly greater improvement in 3MS (6.9 (1.7 to 12.0); t(15) =2.85; p=0.012), IADL (3.4 (1.0 to 5.9); χ21 =7.72; p=0.006), CGI-S (1.4 (0.5 to 2.3), t(16) =3.29; p=0.005), and CGI-I (–2.56 (–3.5 to –1.6), t(17) =–5.72; p<0.001) for rTMS compared to the sham at 4 weeks. The effects of rTMS were durable at 12 weeks.
Conclusion: rTMS may be safely used in subjects with AD and may improve apathy, function, and some aspects of cognition.