Neuromodulation for Apathy in Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study.

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 (5 days/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.