O2-11-02: neuropsychiatric and cognitive symptoms in alzheimer's disease: a study in ad biomarker confirmed patients across the clinical spectrum

Neuropsychiatric symptoms (NPS) are prevalent during the course of Alzheimer's disease (AD). Previous studies using patient samples with potentially mixed etiologies have been inconclusive about relationships between NPS and cognitive deterioration. We therefore investigated cross-sectional and longitudinal associations between NPS and cognition in a large sample of β-amyloid positive patients across the clinical AD spectrum. We included 1,548 patients from the Amsterdam Dementia Cohort (Table 1). All patients were β-amyloid positive (CSF or PET) with a clinical diagnosis of subjective cognitive decline (SCD, N=114), mild cognitive impairment (MCI, N=321), or AD dementia (N=1,113). We measured NPS with the neuropsychiatric inventory (NPI), and cognition across five cognitive domains (Table 1, Figure 1). First, principal component analysis (PCA) was conducted with NPI scores and cognitive domain Z scores at baseline. Second, associations between NPI PCA-components at baseline and cognitive domain scores over time were examined using linear mixed models. Analyses were separated for pre-dementia (SCD, MCI) and dementia. PCA revealed independent cognitive and NPI-components for AD dementia and pre-dementia AD (except for one component including aberrant motor behavior (AMB) and visuospatial abilities in pre-dementia, Tables 2-3). In pre-dementia AD, higher NPI component 3 (nighttime behavior, hallucinations) predicted steeper decline of MMSE scores and executive functions (EF), higher NPI total scores were related to decreased MMSE scores, whereas low NPI component 5 (eating behavior, irritability, apathy) was related to worsening of EF. In AD dementia, higher NPI component 2 (disinhibition, euphoria, AMB) was related to decline in language, higher NPI component 3 (apathy, irritability, nighttime and eating behavior) with decreased MMSE scores, EF, and attention, and higher NPI total scores predicted decline in MMSE, attention, and language (Table 4).