Lateralized tau deposition and speech, language, and cognition: A descriptive case report

Abstract

AbstractBackgroundAsymmetric binding patterns in tau PET imaging are sometimes observed, but less is known about how this asymmetry might explain clinical phenotypes and AD variants, especially in a longitudinal context. Previous work has demonstrated that unilateral tau deposition in left frontal and temporal regions is common in logopenic progressive aphasia (lvPPA), an atypical AD variant. This work presents two descriptive case studies of participants with opposing laterality of [18F]MK‐6240, a PET radioligand for AD neurofibrillary tangles.MethodTwo participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), an ongoing, longitudinal cohort study of late middle‐aged adults enriched for AD risk, were identified based on unilateral MK‐6240 deposition. Topographic amyloid and tau burden was assessed with [11C]PiB and [18F]MK‐6240 PET imaging, respectively. Demographic data, cognitive diagnoses, health histories, and APOE status are described. Longitudinal neuropsychological assessments and digitally recorded connected speech samples were analyzed to create a descriptive profile of cognition and connected speech‐language (CSL). Cognitive test scores and language measures were then compared against the scores of the full WRAP sample, using a robust normative approach previously described by our group.ResultMK‐6240 tau‐PET imaging revealed right‐lateralized tau in Participant A and left‐lateralized tau in Participant B (Figure 1). Participants were identical on all demographics except age and APOE risk of developing AD (though both participants were ApoE‐4 allele carriers) (Table 1). Cognitive assessment Z‐scores (0=mean of demographically similar cognitively stable WRAP participants; Figs 2‐4) depict considerable between visit variability for Participant A on all measures, including language and CSL, with decline from baseline on all but letter fluency. Participant B showed isolated baseline deficits on memory tests (AVLT and story recall) at two standard deviations below the mean, which declined further across visits, whereas performances on Trails, naming, category fluency, and all measures of CSL remained stable and within normal expectations.ConclusionIn this case study, right>left tau PET signal was associated with greater decline in language, particularly connected speech and naming. Future work will examine associations between volumetric MRI and asymmetric regional tau deposition, as well as additional relationships to language and cognition.