Caregiver-Reported Behavioral Changes After Donepezil Transdermal Patch Therapy in Alzheimer’s Disease: An Exploratory Real-World Network Analysis

Tomokazu Shimazu,1 Eri Hoshino,1 Maki Nakaseko,2 Kanako Homma,2 Satoshi Suzuki,2 Kei Horikoshi,1 Yuichi Maruki11Department of Neurology, Saitama Neuropsychiatric Institute, Saitama, Japan; 2Department of Psychiatry, Saitama Neuropsychiatric Institute, Saitama, JapanCorrespondence: Tomokazu Shimazu, Department of Neurology, Saitama Neuropsychiatric Institute, 6-11-1 Honmachi-higashi, Chuo-ku, Saitama, 338-8577, Japan, Tel +81-48-857-6811, Email sni-shimazu@saitama-ni.comPurpose: To characterize caregiver-reported behavioral changes after donepezil transdermal patch therapy and to examine the descriptive connectivity of co-occurring improvements in patients with Alzheimer’s disease (AD).Patients and Methods: This retrospective, single-center observational study included 26 patients meeting the 2011 National Institute on Aging-Alzheimer’s Association criteria for probable AD dementia. Approximately 2– 4 months after patch initiation, caregivers rated nine behavioral domains using routine, non-validated single-item change assessments as improved, unchanged, or worsened relative to the pre-treatment state. A descriptive co-improvement network was used solely to summarize pairwise co-occurrence of binary improvement indicators using phi-coefficients and observed strength centrality. Because of the small sample and sparse binary events, all network measures were treated as sample-specific descriptive quantities rather than inferential estimates.Results: The most frequently improved domains were smiling/positive affect (12/26, 46.2%), calmness (9/26, 34.6%), and night-time sleep (8/26, 30.8%). Calmness had the highest observed strength centrality (2.467), followed by grooming behavior (2.059), hobbies/interests (2.009), and housework/instrumental activities of daily living (1.938). Calmness remained the highest-strength node in all 26 leave-one-participant-out sensitivity analyses. No treatment discontinuations or serious adverse events were documented.Conclusion: Caregiver-perceived calmness, assessed as a single non-validated change item, was the most highly connected domain in this small descriptive co-improvement network. The findings are exploratory and do not establish treatment efficacy, a validated agitation-related outcome, temporal direction, or mechanism. Prospective studies using standardized behavioral measures are needed.Keywords: Alzheimer’s disease, behavioral and psychological symptoms of dementia, caregiver-reported outcome, donepezil transdermal patch, exploratory network analysis