Abstract
Anosognosia, the lack of awareness of memory decline, and Neuropsychiatric Symptoms (NPS) are prevalent and debilitating symptoms in Alzheimer's disease (AD) dementia. Understanding the coexistence of these symptoms may help guide clinical interventions and treatment strategies. This study aimed to compare NPS prevalence in patients with and without anosognosia at baseline and to assess the association between anosognosia and NPS over time. We examined patients with AD dementia enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To be included in the current study, patients had to have undergone baseline assessments and at least one subsequent follow-up evaluation. Furthermore, all patients had to have amyloid (as assessed using Positron Emission Tomography, PET), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), and Everyday Cognition (ECog) variables available throughout the study. Anosognosia, our exposure of interest, was determined using Ecog scores from patients and study partners. Study partners evaluated the presence or absence of 12 NPS (our outcomes of interest) using the NPI. Cox proportional hazards models, excluding patients who had any symptoms of NPS at baseline, were used to evaluate NPS onset by group (anosognosia/no anosognosia) while adjusting for age, sex, years of education, and MMSE. 112 patients with follow-up data (mean = 1 year) were included in this study. Of these, 47.3% (n = 53) had anosognosia, while 52.7% (n = 59) did not. In those with anosognosia at baseline, we observed a trend toward greater prevalence of agitation and motor symptoms. Exploratory time-to-event analysis demonstrated that the patients with anosognosia had a faster onset of apathy (HR: 2.78, 95% CI: 1.37-5.62, p = 0.01) compared to the patients without anosognosia. In this exploratory study, while there were no significant differences in frequency of NPS at baseline between the groups, patients with anosognosia demonstrated faster onset of apathy as compared to patients without anosognosia. These findings underscore the importance of longitudinal assessments and tailored interventions targeting the management of NPS in AD dementia patients with anosognosia. Further research is warranted to explain the underlying mechanisms driving these associations and to inform the development of targeted therapeutic strategies aimed at improving patient outcomes in this population.