Background: There is an increased effort to better understand neuropsychiatric symptoms
of Alzheimer’s Disease (AD) as an important feature of symptomatic burden as well as potential modifiable
factors of the disease process. Anxiety is one of the most common neuropsychiatric symptoms in
Alzheimer’s Disease (AD). A growing body of work has emerged that addresses the epidemiology and
biological correlations of anxiety in AD.
Methods: Here, we review human studies in research and clinical cohorts that examined anxiety in
AD. We focused on work related to prevalence across AD stages, correlation with established biomarkers,
relationship with AD neuropathology and genetic risk factors, and impact on progression.
Results: Anxiety is prominent in the early stages and increases across the spectrum of functional
stages. Biomarker relationships are strongest at the level of FDG-PET and amyloid measured via PET
or cerebrospinal fluid analysis. Neuropathologically, anxiety emerges with early Braak stage tau pathology.
The presence of the apolipoprotein E e4 allele is associated with increased anxiety at all
stages, most notably at mild cognitive impairment. Anxiety portended a faster progression at all predementia
Conclusion: This body of work suggests a close biological relationship between anxiety and AD that
begins in early stages and influences functional decline. As such, we discuss future work that would
improve our understanding of this relationship and test the validity of anxiolytic treatment as disease
modifying therapy for AD.