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This case report presents the story of Mr. S, a professional orchestral musician with declining musical sight-reading ability, followed by progressive visuospatial and language deficits. Our novel musical assessment battery revealed deficits in music-reading (musical alexia) and music-writing (musical agraphia), with spared auditory perception and expression. Taken with neuropsychological testing, clinical history, and imaging, we conclude that his symptoms evolved from musical alexia to a multidomain, neurodegenerative process centered in the dominant inferior parietal lobe and temporoparietal junction. We suspect a primary TDP-opathy with comorbid preclinical Alzheimer's disease. Mr. S's case highlights musical symptoms as meaningful, early indicators of neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Affective cognition and emotion processing is impaired in amnestic Alzheimer's disease (AD), although less is known about atypical (AT) variants such as logopenic variant primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA). The affective blindsight pathway bypasses V1 via the superior colliculus‐pulvinar route to activate the amygdala in cases of occipital lesioning and may explain maintenance of emotion identification and visual information processing in non‐amnestic AD despite atrophy in visuospatial regions. We sought to characterize functional connectivity from key regions along the affective blindsight pathway in a clinically heterogeneous AD cohort. Method: We collected structural, resting‐state, and task functional MRI scans where participants viewed affective face and neutral scene images, and neuropsychological data in individuals with clinically heterogeneous AD (8 lvPPA, 9 PCA) and age‐matched healthy controls (24 HC). We assessed connectivity from 4mm radius seeds located along the affective blindsight pathway (superior colliculus, medial pulvinar, and amygdala) using CONN toolbox. Two‐sample t‐tests were used to compute group‐level differences (AT > HC; p < 0.05/0.05), using w‐scores to correct for atrophy. Result: As expected, AT participants performed significantly worse on visuospatial tasks outside the scanner (WAIS‐III Blocks Design, Benson Complex Figure Copy immediate recall; p < 0.01). During resting state scans, the AT group had relatively lower connectivity to visuospatial regions including the lateral occipital cortex, angular gyrus, and precuneus from the superior colliculus and medial pulvinar seeds. During the scenes/faces task, they displayed relatively higher connectivity to those same visuospatial regions. From the amygdala seed, the AT group had higher connectivity to area V1 during the resting state scan and lower connectivity to frontal lobe regions during scenes/faces. Conclusion: We explored functional connectivity of the affective blindsight pathway in a clinically heterogeneous AD cohort. Connectivity was relatively higher in the AT group from the superior colliculus, medial pulvinar, and amygdala to occipital lobe regions commonly atrophied in PCA and lvPPA, suggesting a function of this pathway may be to compensate for disease‐related atrophy. While preliminary, these findings hint that the blindsight pathway may serve a compensatory function in atypical AD. [ABSTRACT FROM AUTHOR]

Background: While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms., Methods: We examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In our tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores., Results: Amyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala ( F (4,442)=14.61, p =0.00045; F( 4,442)=5.83, p =0.024, respectively). Across amygdalar divisions, amyloid-positive individuals had relatively increased regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex. There was an interaction by amyloid group between tau binding in the medial and lateral amygdala and anxiety. Medial amygdala to retrosplenial connectivity negatively correlated with anxiety symptoms (r s =-0.103, p =0.015)., Conclusions: Our findings suggest that preclinical tau deposition in the amygdala may result in meaningful changes in functional connectivity which may predispose patients to mood symptoms., Competing Interests: DISCLOSURES WX is currently employed in a fellowship role at Unlearn. AI Inc. JL, ST, BFT, SW, CH, TT, SN, CZ, YZ, AP, EB, and CF have no conflicts of interest or financial interests to declare.