Memory, social cognition, and beyond: Neuropsychological markers differentiating Alzheimer's disease and frontotemporal dementia

Vollständiger Abstract

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Background Distinguishing Alzheimer's disease (AD) from frontotemporal dementia (FTD) remains a major clinical challenge, particularly in early disease stages due to overlapping symptoms. Although neuropsychological assessment is central to diagnosis, brief cognitive screening instruments often emphasize episodic memory, whereas comprehensive neuropsychological assessment encompasses multiple cognitive domains. Nevertheless, social cognition and other relevant functions may remain underrepresented in routine clinical assessment. Objective To identify neuropsychological domains and test procedures that reliably differentiate AD from FTD and support differential diagnosis. Methods A systematic PubMed literature search was conducted using predefined inclusion and exclusion criteria. Original studies directly comparing neuropsychological performance in patients with AD and FTD were included. Owing to methodological heterogeneity, findings were synthesized narratively. Results A total of 322 records were identified, of which 80 studies met the inclusion criteria. A clear domain-specific pattern emerged. Episodic memory impairment, particularly delayed recall deficits, consistently distinguished AD from FTD, with poorer performance in AD. In contrast, deficits in social cognition, including theory of mind and emotion recognition, were more pronounced in FTD and were often detectable early in the disease course. Executive functions and language showed heterogeneous findings, with discriminative value depending on specific subdomains and FTD subtypes. Visuospatial functions and attention provided supportive but less consistent differentiation, while global screening instruments showed limited diagnostic specificity. Conclusions Differentiation between AD and FTD should not rely on single cognitive domains. The most clinically meaningful distinction is achieved through a multidimensional assessment integrating episodic memory, social cognition, and selected executive and behavioral measures.