ObjectiveTo examine the efficacy and safety of combined transcranial direct current stimulation (tDCS) and working memory training (WMT) in enhancing the cognitive functions for individuals with mild neurocognitive disorder due to AD (NCD‐AD).MethodsIn this double‐blind, sham‐controlled randomized clinical trial (RCT), 201 patients with NCD‐AD were randomly assigned for a 4‐week intervention of either a combination of tDCS and WMT, sham tDCS and WMT, or tDCS and control cognitive training (CCT). Global cognition and domain‐specific cognitive function were assessed before and after the intervention with Alzheimer's disease assessment scale‐cognitive subscale (ADAS‐Cog), category verbal fluency test, logical memory, digit, and visual span tests.ResultsStudy participants did not show intervention group differences in baseline demographics, or cognitive characteristics (ANOVA). Cognitive enhancement was found across three groups after 4 weeks intervention. Combined tDCS‐WMT group showed significantly greater improvement compared with single‐modality groups in delayed recall (P = 0.043, η 2 = 0.036) and working memory capacity (P = 0.04, η 2 = 0.038) at 4th week, and logical memory at 12th week (P = 0.042, η 2 = 0.037). Adverse events, including skin lesions (2.2%), were similar between groups.InterpretationtDCS or WMT could be a safe, feasible, and effective intervention for individuals with NCD‐AD. A combination of tDCS and WMT presents greater cognitive enhancement, which may highlight the potential synergistic effects of combined modality intervention on cognition.

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BackgroundNon‐invasive brain stimulation (NIBS) is increasingly used as a probe of function and therapeutics in experimental neuroscience and neurorehabilitation. Scalp‐to‐cortex distance (SCD), as a key parameter, has been shown to potentially impact on the electric field. This study aimed to examine the region‐specific SCD and its relationship with cognitive function in the context of age‐related brain atrophy.MethodsWe analyzed the SCD and cortical thickness (CT) of left primary motor cortex (M1) in 164 cognitively normal (CN) adults and 43 dementia patients drawn from the Open Access Series of Imaging Studies (OASIS). The degree of brain atrophy was measured by the volume of ventricular system. Computational head model was developed to simulate the impact of SCD on the electric field.ResultsIncreased SCD of left M1 was only found in dementia patients (P < .001). When considering CT, the ratio of SCD to CT (F = 27.41, P < .001) showed better differential value than SCD. The SCD of left M1 was associated with worse global cognition (r = −.207, P = .011) and enlarged third ventricle (r = .241, P < .001). The electric field was consequently reduced with the increased SCD across cognitively normal elderly and dementia groups.ConclusionsScalable distance measures, including SCD and CT, are markedly correlated with reduced electric field in dementia patients. The findings suggest that it is important to be aware of region‐specific distance measures when conducting NIBS‐based rehabilitation in individuals with brain atrophy.

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