The behavioral variant of Alzheimer disease is clinically most like behavioral variant frontotemporal dementia (bvFTD) and is pathophysiologically most similar to typical Alzheimer disease (tAD), according to a systematic review and meta-analysis published in JAMA Neurology.

The authors searched PubMed/MEDLINE and Web of Science databases for studies of clinically diagnosed AD cases with frontal or behavioral presentations or bvFTD cases with neuropathological evidence of AD. Studies included patients with early and predominant behavioral changes with suspect AD. A total of 83 studies met inclusion criteria, and 13 were included in the meta-analysis, which compared patients with bvAD, and patients with tAD or bvFTD.  The studies included 591 patients (aged 62.0±7.3 years 38.2% women) with bvAD.

The meta-analysis showed that patients with bvAD experienced more severe behavioral and neuropsychiatric symptoms compared with patients with tAD (SMD 1.16 P <.001). Differences in severe behavioral/neuropsychiatric symptoms of bvAD and bvFTD were negligible.

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Patients with bvAD were less likely to have compulsive behaviors and hyperorality but were alike in disinhibition, apathy, and lack of empathy compared with patients who had bvFTD. Patients with bvAD were more likely to show agitation, hallucinations, and delusions compared with patients with bvFTD. Patients with bvAD were more likely to show nighttime behaviors, euphoria, anxiety, agitation, hallucinations, delusions, and motor behaviors compared with patients with tAD.

Patients with bvAD did not have significantly different Mini-Mental State Exam (MMSE) scores compared with patients with tAD or bvFTD. Those with bvAD had lower executive performance scores compared with patients with tAD. Patients with bvAD tended to have worse memory performance compared with patients with bvFTD.

The investigators found that bvAD and tAD were most similar when they analyzed amyloid-PET, tau PET, and neuropathology meta-analyses. They saw that bvAD neuroimaging manifests predominantly like that of AD in the bilateral temporoparietal areas with minimal involvement of the frontal cortex, followed by a pattern similar to that of bvFTD, with the posterior and anterior regions of the brain networks involved in socioemotional processing.

The researchers recommended psychiatrists complete a full neuropsychological evaluation of patients to objectively confirm memory or executive functioning areas to distinguish it from tAD or bvFTD. They said 2 of the following behavioral features are required to diagnose bvAD: disinhibition, apathy, lack of empathy, compulsiveness, and hyperorality.

To declare definite bvAD, doctors must identify a histopathological indication of AD as the primarily pathology and a genetic variant associated with familial AD, researchers said.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Ossenkoppele R, Singleton EH, Groot C, et al. Research criteria for the behavioral variant of Alzheimer disease: a systematic review and meta-analysis. JAMA Neurol. Published online December 6, 2021. doi:10.1001/jamaneurol.2021.4417