Anosognosia, and Neuropsychiatric Symptoms in the Alzheimer's Disease Spectrum

Abstract

Abstract: Background: Anosognosia, which is the lack of awareness of memory decline, and Neuropsychiatric Symptoms (NPS) are prevalent and debilitating symptoms in Alzheimer’s disease (AD) dementia. Understanding the co-existence 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 assess the association between anosognosia and NPS. Methods: We examined patients with AD dementia enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). To be included in the study, participants needed to undergo baseline assessments and at least one subsequent follow-up evaluation. Furthermore, all patients had to have amyloid (SUVr), MMSE, NPI, and ECog variables available throughout the study. Anosognosia, our exposure of interest, was determined using Everyday Cognition (Ecog) scores from participants and study partners. Study partners evaluated the presence or absence of 12 NPS (our outcomes of interest) using the Neuropsychiatric Inventory (NPI). Cox proportional hazard models evaluated NPS development by anosognosia status and were adjusted for age, sex, years of education, and MMSE. Participants who exhibited any symptom from the 12 NPS at baseline were excluded from the Cox models. Results: We included 112 participants with follow-up data (mean = 1. years). Of these, 47.3% (n = 53) had anosognosia, while 52.7% (n = 59) did not. In those with anosognosia at baseline, we observed tendencies toward a greater prevalence of agitation and motor symptoms. However, in time-to-event analysis, there was no association of anosognosia versus not with development of any of the NPS. Conclusion: While AD dementia patients with anosognosia exhibited higher agitation and motor symptoms at baseline, the development of NPS did not significantly differ between AD dementia patients with and without anosognosia in the survival analysis. Abstract: Background: Alzheimer's disease (AD) is characterized by cognitive decline, with amyloid-beta (Aβ) pathology implicated in the disease process. Individuals with AD often experience neuropsychiatric symptoms (NPS) and a lack of awareness (anosognosia) regarding their memory decline. The relationship between NPS and anosognosia is thought to share a common neurobiological basis. This study aimed to investigate the associations between Aβ pathology, anosognosia, and NPS across the clinical AD spectrum. Methods: We analyzed data from 1691 individuals in the Alzheimer’s Disease Neuroimaging Initiative (ADNI); 703 of them were cognitively normal (CN), while 988 had symptoms (Mild Cognitive impairment (MCI) and AD dementia patients). Our exposure: Aβ burden measured with Standardized Uptake Value ratio (SUVr) in brain regions aggregates was assessed using [18F] florbetapir (FBP) PET scans in specific brain regions, including the frontal, cingulate, lateral parietal, and lateral temporal. We used the occipital lobe as a control area. Our study outcomes were measures of anosognosia and NPS. Anosognosia was evaluated using Everyday Cognition (ECog) test scores, while NPS was assessed through the Neuropsychiatric Inventory (NPI). To investigate the joint association of amyloid burden on awareness and NPS, we applied Multivariate Multiple Regressions (MMR) analyses. Results: In CN individuals, higher Aβ burden (SUVr) was associated with heightened awareness of memory decline in specific brain regions (frontal, cingulate, lateral parietal, and lateral temporal), with no significant association with NPS. In symptomatic individuals, higher Aβ pathology (SUVr) was associated with lower awareness and increased NPS in all brain regions examined. MMR analyses showed that SUVr Aβ levels were predictive of both lower awareness and a higher NPS in the symptomatic group across these specific brain regions. Conclusion: These results suggest that anosognosia and higher NPS in symptomatic individuals (MCI and AD dementia patients) could be related to amyloid accumulation in these vulnerable brain regions.