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PurposeIn vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD).MethodsForty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum.ResultsSUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient.ConclusionPreliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

ObjectiveTo compare recognition of facial expression (FE) vs recognition of facial identity (FI) in posterior cortical atrophy (PCA), with the hypothesis that FE recognition would be relatively preserved in PCA.MethodsIn this observational study, FI and expression recognition tasks were performed by 194 participants in 4 groups, including 39 with Alzheimer disease (AD) (non-PCA), 49 with behavioral variant frontotemporal dementia (bvFTD), 15 with PCA, and 91 healthy controls. Between-group differences in test scores were compared.ResultsPatients with PCA performed worse than healthy controls in FI and emotion recognition tasks (p < 0.001 for all). Patients with PCA also performed worse than AD and bvFTD groups in FI recognition, with no difference in FE recognition.ConclusionsPatients with PCA have relatively preserved FE recognition compared to FI recognition, as seen in affective blindsight.

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]

BackgroundPosterior cortical atrophy (PCA) is a clinical variant of Alzheimer's disease (AD) that presents with progressive visuospatial symptoms. While amnestic AD is characterized by disrupted default mode network (DMN) connectivity with corresponding increases in salience network (SN) connectivity, a visuospatial network appears to be disrupted early in PCA. Based on PCA patients' clinical features, we hypothesized that, in addition to early decreased integrity within the visuospatial network, patients with PCA would show increases in SN connectivity despite relative preservation of DMN. As the lateral pulvinar nucleus of the thalamus has direct anatomical connections with striate and extrastriate cortex and DMN, and the medial pulvinar is anatomically interconnected with SN, we further hypothesized that lateral and medial pulvinar nuclei might be implicated in intrinsic connectivity changes in PCA.Methods26 patients with PCA and 64 matched controls were recruited through UCSF Memory and Aging Center research programs. Each completed a standardized neuropsychological battery, structural MRI, and task-free fMRI. Seed-based functional correlations were used to probe networks of interest, including those seeded by the medial and lateral pulvinar thalamic nuclei, across the whole brain, and functional data analyses were adjusted for brain atrophy.ResultsPatients with PCA showed disproportionate deficits in the visuospatial domain; they also showed preserved social sensitivity and endorsed more depressive symptoms than HCs. PCA patients had significant parietooccipital atrophy accompanied by widespread connectivity decreases within the visuospatial network, enhanced connectivity between some structures in SN, and enhanced connectivity between key nodes of the DMN compared to controls. Increased SN connectivity correlated with a measure of social sensitivity, and increased DMN connectivity correlated with short-term memory performance. Medial pulvinar connectivity increases in PCA were topographically similar to SN (anterior insula) connectivity increases, while lateral pulvinar connectivity increases were similar to DMN (posterior cingulate) connectivity increases.ConclusionsPCA is characterized by preserved to heightened connectivity in the SN and DMN despite decreased visuospatial network connectivity. The spatial similarity of medial and lateral pulvinar connectivity changes to those seen in the SN and DMN suggests a role for the pulvinar in intrinsic connectivity network changes in PCA.

IntroductionAffective changes precede cognitive decline in mild Alzheimer's disease and may relate to increased connectivity in a "salience network" attuned to emotionally significant stimuli. The trajectory of affective changes in preclinical Alzheimer's disease, and its relationship to this network, is unknown.MethodsOne hundred one cognitively normal older adults received longitudinal assessments of affective symptoms, then amyloid-PET. We hypothesized amyloid-positive individuals would show enhanced emotional reactivity associated with salience network connectivity. We tested whether increased global connectivity in key regions significantly related to affective changes.ResultsIn participants later found to be amyloid positive, emotional reactivity increased with age, and interpersonal warmth declined in women. These individuals showed higher global connectivity within the right insula and superior temporal sulcus; higher superior temporal sulcus connectivity predicted increasing emotional reactivity and decreasing interpersonal warmth.ConclusionsAffective changes should be considered an early preclinical feature of Alzheimer's disease. These changes may relate to higher functional connectivity in regions critical for social-emotional processing.

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]