Neuropsychiatric symptoms (NPS), including depression, apathy, and anxiety, are common among individuals with Alzheimer’s dementia (AD). It is not yet clear the relationship among NPS, cognitive symptoms, and AD neuropathology (which includes amyloid beta deposits, neurofibrillary tangles composed of hyperphosphorylated tau, and neurodegeneration). In this article, Johansson and colleagues studied 356 cognitively unimpaired older adults (age 60 or older with Mini-Mental State Exam (MMSE) scores of 28-30) over a period of 8 years. Apathy (measured using the self AES-S and informant AES-I), anxiety and depression (measured using the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) as well as cognition (measured using the MMSE and the Preclinical Alzheimer-s Cognitive Composite (mPACC5)) were evaluated every 2 years. Levels of cerebrospinal fluid (CSF) amyloid beta-42 (AB42), AB40 and Neurofilament Light (NfL), and magnetic resonance imaging for white matter lesions (WML) were taken at baseline. It was found that longitudinal increases in apathy scores on the AES-I and in anxiety on the HADS-A correlated with lower CSF AB42/40 (which indicates higher AB deposition in the brain) and higher (more abnormal) CSF levels of NfL. Higher WML volumes were associated with increased longitudinal apathy as rated on the AES-S. There was no association between baseline pathology and depression (HADS-D) scores. Worsening of apathy was largely independent of change in cognition, indicating that change in cognition does fully not mediate the longitudinal worsening of apathy. These data indicate that AD pathology, and especially AB pathology, may have a detrimental effect on the worsening of NPS (especially apathy) over time. The authors suggest that NPS may predict future cognitive decline and that apathy may be due to pathology in the frontoparietal control network. Although further investigation is needed, this study provides elucidation on the complex relationship between NPS, cognition, and AD pathology.

Reference:
Johansson M et al. Biological Psychiatry 2022; Epub ahead of print. Abstract