BACKGROUND: The effect of cultural differences in neurodegenerative diseases is not well understood. We aimed to investigate the cognitive profiles of English- and Spanish-speaking individuals with primary progressive aphasia (PPA). METHODOLOGY: A comparative cross-sectional study was conducted with 461 participants: 215 participants from Australia and 246 from Spain. The Australian cohort included 131 PPA patients: 37 nonfluent PPA (nfvPPA), 49 semantic PPA (svPPA), 45 logopenic (lvPPA) and 84 healthy controls (HC)
the Spanish cohort had 162 PPA: 64 nfvPPA, 31 vsPPA, 67 lvPPA, and 84 HC. All participants completed the ACE-III and other tests assessing verbal working memory, attention/executive functioning, visuospatial constructional abilities and episodic memory. A subgroup of participants underwent structural brain MRI. Cognitive performance and neuroimaging were compared between groups. RESULTS: The most salient differences between each variant and HC were similar in the Australian and Spanish cohort. However, the Spanish cohort scored lower than the Australian cohort in most cognitive tests evaluated (ACE-III total, attention, memory and visuospatial in nfvPPA
attention, memory, and visuospatial in svPPA
and memory, language, and visuospatial in lvPPA). Differences were particularly pronounced in the visuospatial subdomain among nonfluent variant PPA. Cortical thickness analysis showed the expected regional atrophy in each PPA variant, but with no greater atrophy in the Spanish cohort. CONCLUSION: These findings revealed an impairment in other cognitive domains beyond language in PPA. However, Spanish patients exhibited more generalized cognitive involvement despite similar demographic and neuroimaging profiles, suggesting that cultural and resilience factors may influence PPA presentations.