Individuals with Lewy Body Dementia (LBD) have cognitive fluctuations caused in part by cholinergic denervation. Cholinesterase inhibitors can improve cognition in LBD but are limited by nonspecific location targeting and side effects. High-definition transcranial direct current stimulation (HD-tDCS), a noninvasive neuromodulation method, offers a feasible treatment option because it can target affected regions with minimal side effects. We investigated the physiological and cognitive effects of HD-tDCS in seven older adults diagnosed with LBD. We individualized HD-tDCS montages to target areas of low cholinergic innervation identified via positron emission tomography (PET), with the hypothesis that enhancing functioning in these areas may reduce the characteristic cognitive fluctuations and enhance measures of complex attention.

To date, seven older adults (mean age = 75.29 ±7.50) diagnosed with LBD have been enrolled. All participants were taking cholinesterase inhibitors and were not prescribed anti-cholinergic medications. We identified areas of cholinergic denervation using vesicular acetylcholine transporter (VAChT) PET ligand and developed individualized montages that targeted these regions using finite element models of each participant’s structural magnetic resonance imaging (MRI) scan. Each participant completed ten 20-minute stimulation sessions over a two- or three-week period (4-5 sessions the first week and 3-5 sessions the remaining weeks). Participants completed the Dementia Cognitive Fluctuation Scale (DCFS) and Montreal Cognitive Assessment (MoCA). We used the n-back task as a probe of working memory ability. Four participants were able to complete an n-back task during functional (f)MRI pre and post stimulation while one other completed the n-back task during functional near-infrared spectroscopy (fNIRS) post-stimulation in lieu of fMRI.

Wilcoxon signed-rank test comparing key questions of the DCFS revealed a statistically significant improvement in cognitive fluctuations post- relative to pre-stimulation (Z=2.388, p=0.017). In contrast, MoCA total scores showed no significant change from pre- to post-stimulation (Z=0.736, p=0.461). Total accuracy on the 2-back task, three participants improved from pre- to post-stimulation and one showed a nominal decline (Z=1.461, p=0.144). Of the four participants who completed task-based fMRI, three showed a widespread increase of activation during both the 0-back and 2-back tasks. Specifically, two participants showed increased activation within the frontoparietal network and one participant in the prefrontal and temporal cortices. fNIRS revealed increased activation in the left superior temporal gyrus and the inferior frontal gyrus during the 2-back and superior frontal gyrus during 0-back.

Our initial findings suggest that individualized HD-tDCS may mitigate cognitive fluctuations in those with Lewy Body Dementia by enhancing regional and, perhaps, network-based functioning. We plan to expand this cohort and identify patient-level predictors of response that may help those with LBD optimize their cognitive functioning.