Longitudinal trajectories of cognitive, functional, and neuropsychiatric decline in Alzheimer’s disease during COVID-19 lockdown in South Korea

The progression of Alzheimer's disease (AD) and its interaction with COVID-19-induced social isolation remains poorly understood. This study investigated the longitudinal trajectories of AD severity on cognitive function, functional ability, and neuropsychiatric symptoms, and examined the impact of COVID-19 lockdown on AD patients in South Korea. In this retrospective longitudinal study, data from 253 adults (aged ≥ 55) diagnosed with mild cognitive impairment (MCI) or AD were analyzed, collected between 2018 and 2022. Participants were classified into four groups based on clinical dementia rating (CDR) scores: MCI, AD-CDR0.5, AD-CDR1, and AD-CDR2. Cognitive function, functional abilities, neuropsychiatric symptoms, depressive symptoms, and overall dementia severity were assessed. Linear mixed-effects models, along with mediation and moderation analyses were employed to analyze the data. Significant trajectories of decline in cognitive function and functional abilities were observed over time, with more pronounced declines in higher AD severity groups. The COVID-19 lockdown exacerbated cognitive decline and impairment in activities of daily living (ADL) specifically in the most severe AD group (AD-CDR2). Instrumental activities of daily living (IADL) mediated the relationship between mini-mental state examination (MMSE) scores and CDR sum of boxes (CDR-SB) in the MCI, AD-CDR0.5, and AD-CDR1 groups. A significant interaction between MMSE scores and neuropsychiatric symptoms was observed in the moderate AD group (AD-CDR1), indicating that worsening neuropsychiatric symptoms intensified cognitive decline. Neuropsychiatric Inventory (NPI) scores increased over time, indicating worsening neuropsychiatric symptoms, whereas depressive symptoms, measured by the short geriatric depression scale (SGDS), remained stable over the study period. This study highlights the impact of AD severity on cognitive and functional decline, further exacerbated by the COVID-19 lockdown. The mediating role of IADL suggests that maintaining complex daily activities may be crucial in slowing disease progression in AD patients. Additionally, the worsening of neuropsychiatric symptoms underscores the need for targeted mental health support, especially during periods of social isolation, to mitigate adverse effects on patients and caregivers.