Sex Differences in Sleep and Circadian Activity Patterns in MCI due to Alzheimer’s and Lewy Body Disease

Objectives: This study aimed to explore sex-related differences in mild cognitive patients due to Alzheimer's Disease (MCI-AD) and due to Dementia Lewy Body (MCI-DLB). Materials and Methods: This observational study included patients with MCI-AD and MCI- DLB from Policlinico Tor Vergata and Policlinico Umberto I. Patients wore an actigraph on the non-dominant wrist for 7 days and completed a sleep diary. All patients underwent neuropsychological evaluation (including Mini-Mental State Examination MMSE) and completed a battery of self-report questionnaires to assess excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) and perceived sleep quality (Pittsburgh Sleep Quality Index, PSQI). All patients were compared with a control group without sleep disorders or neurodegenerative or psychiatric conditions. As data were not normally distributed, group comparisons and sex differences within each group were analysed using the Kruskal-Wallis test and Mann–Whitney U test. Results: The study included 14 MCI-AD patients (57.1% male; mean age 72.07 ± 6.33 years, MMSE 23.85 ± 4.24), 22 MCI-DLB patients (59.1% male; mean age 79.59 ± 7.62 years, MMSE 26.00 ± 2.26), and 16 controls (56.3% male; mean age 67.63 ± 6.34 years, MMSE 29.66 ± 0.77). Group comparisons showed higher PSQI scores in MCI-DLB patients compared to controls (p=0.001), greater nocturnal wake time (p=0.033) in MCI-AD compared to MCI-DLB, and both a lower day–night activity ratio (p=0.001) and higher fragmentation index (p=0.021) in MCI-AD compared to controls. Among MCI-AD patients, females showed significantly greater wake time during the night compared to males (p = 0.043). In the MCI-DLB group, females exhibited higher average activity during the most active 10-hour period (M10; p = 0.02), higher relative amplitude (RA; p = 0.06), and lower inter daily variability (IV; p = 0.09) than males MCI-DLB. Among controls, females also showed higher M10 values (p = 0.42) and significantly lower RA (p = 0.042) than males. No significant sex differences were observed in ESS scores in either group. However, among MCI-DLB patients, females reported significantly poorer sleep quality on the PSQI compared to males. Discussion: Findings suggest sex-related differences in rest–activity patterns and sleep fragmentation in both MCI-AD and MCI-DLB. Females with MCI-AD showed greater nocturnal wakefulness, possibly reflecting more fragmented sleep. In contrast, MCI-DLB females displayed more stable circadian activity and reported poorer subjective sleep quality. These patterns may reflect both neurodegenerative pathology and sex-specific factors. Conclusions: Sex-related differences in sleep and circadian patterns are present in MCI-AD and MCI-DLB. These preliminary findings highlight the need to consider sex in the clinical assessment of neurodegenerative conditions.