Language deficits across PET-based Braak stages of tau accumulation in Alzheimer's disease

INTRODUCTIONWidespread language complaints in the cognitively unimpaired (CU) may reflect Alzheimers Disease (AD) pathology and future objective impairments. METHODS138 CU, 45 mild cognitive impairment and 28 dementia participants from the TRIAD cohort underwent 18F-MK-6240 tau-PET and 18F-AZD-4694 amyloid-PET. Word-finding complaints, confrontation naming, semantic and phonemic fluency and word-knowledge were evaluated. Covariance, direct and stepwise discriminant, and voxel-wise regression analyses were conducted. RESULTSWord-finding complaints appeared in early tau stages (Braak 1-2), followed by naming difficulties (Braak 3-4), and widespread language impairments in later stages (Braak 5-6). Complaints over forgetting the names of objects, naming, and APOE significantly improved classification of early AD pathology. In CU, complaints over forgetting names of objects were linked to left fusiform and inferior temporal gyri tau accumulation. DISCUSSIONLanguage measures are useful in detecting and tracking AD-related pathophysiologies. Results encourage refinement of clinical tools for early detection and disease monitoring. HighlightsLanguage decline parallels tau buildup across PET-based Braak stages of AD. Subjective anomia marks earliest tau-related language symptom (Braak 1-2). Objective naming deficits emerge in the middle tau spread stages (Braak 3-4). Advanced tau spread reflects significant and widespread language impairments. Word-finding complaints correlate with left fusiform and inferior temporal tau. Research in contextSystematic review: The literature was reviewed using traditional sources. The core biological definition of Alzheimers disease (AD) has recently been linked to its defining cognitive clinical features of episodic memory impairments. Widespread subjective language complaints amongst cognitively unimpaired (CU) older adults and objective language impairments observed across the AD continuum suggests these measures and the further bridging of biological and clinical definitions of AD could play a critical, cost-effective role in disease detection and monitoring. Interpretation: Results extend to tau previous findings describing language changes in AD and related to amyloid status and grey-matter atrophy. They also establish the likely staging of language impairments across the biological AD continuum. Future directions: The manuscript contextualises the use of subjective word-finding complaints, alongside genetic risks to significantly enhance the prediction of underlying AD related pathology in CU. Languages measures used in clinical practice remain limited however and better test should be utilized and developed.