Tau PET imaging predicts cognition in atypical variants of Alzheimer's disease.

Accumulation of paired helical filament tau contributes to neurodegeneration in Alzheimer's disease (AD). 18 F-flortaucipir is a positron emission tomography (PET) radioligand sensitive to tau in AD, but its clinical utility will depend in part on its ability to predict cognitive symptoms in diverse dementia phenotypes associated with selective, regional uptake. We examined associations between 18 F-flortaucipir and cognition in 14 mildly-impaired patients (12 with cerebrospinal fluid analytes consistent with AD pathology) who had amnestic (n = 5) and non-amnestic AD syndromes, including posterior cortical atrophy (PCA, n = 5) and logopenic-variant primary progressive aphasia (lvPPA, n = 4). Amnestic AD patients had deficits in memory; lvPPA in language; and both amnestic AD and PCA patients in visuospatial function. Associations with cognition were tested using sparse regression and compared to associations in anatomical regions-of-interest (ROIs). 18 F-flortaucipir uptake was expected to show regionally-specific correlations with each domain. In multivariate analyses, uptake was elevated in neocortical areas specifically associated with amnestic and non-amnestic syndromes. Uptake in left anterior superior temporal gyrus accounted for 67% of the variance in language performance. Uptake in right lingual gyrus predicted 85% of the variance in visuospatial performance. Memory was predicted by uptake in right fusiform gyrus and cuneus as well as a cluster comprising right anterior hippocampus and amygdala; this eigenvector explained 57% of the variance in patients' scores. These results provide converging evidence for associations between 18 F-flortaucipir uptake, tau pathology, and patients' cognitive symptoms.

When and how did you go wrong? Characterizing mild functional difficulties in older adults during an everyday task.

Mild functional difficulties associated with cognitive aging may be reliably measured by coding "micro-errors" during everyday tasks, like meal preparation. Micro-errors made by 25 older adult and 48 younger adults were coded on four dimensions to evaluate the influence of: 1) poor error monitoring; 2) goal decay; 3) competition for response selection when switching to a new subtask; and 4) interference from distractor objects. Micro-errors made by young adults under a dual task load also were analyzed to determine the influence of overall performance level. Older adults' micro-errors were observed when switching to a new subtask and to unrelated distractors. Slowed error monitoring and goal decay also influenced micro-errors in older adults, but not significantly more so than younger adults under the dual task. Interventions to reduce interference from distractors and to increase attention at critical choice points during tasks may optimize everyday functioning and preclude decline in older adults.

Multimodal in vivo and postmortem assessments of tau in Lewy body disorders.

We compared regional retention of 18F-flortaucipir between 20 patients with Lewy body disorders (LBD), 12 Alzheimer's disease patients with positive amyloid positron emission tomography (PET) scans (AD+Aß) and 15 healthy controls with negative amyloid PET scans (HC-Aß). In LBD subjects, we compared the relationship between 18F-flortaucipir retention and cerebrospinal fluid (CSF) tau, cognitive performance, and neuropathological tau at autopsy. The LBD cohort was stratified using an Aß42 cut-off of 192 pg/mL to enrich for groups likely harboring tau pathology (LBD+Aß = 11, LBD-Aß = 9). 18F-flortaucipir retention was higher in LBD+AB than HC-Aß in five, largely temporal-parietal regions with sparing of medial temporal regions. Higher retention was associated with higher CSF total-tau levels (p = 0.04), poorer domain-specific cognitive performance (p = 0.02-0.04), and greater severity of neuropathological tau in corresponding regions. While 18F-flortaucipir retention in LBD is intermediate between healthy controls and AD, retention relates to cognitive impairment, CSF total-tau, and neuropathological tau. Future work in larger autopsy-validated cohorts is needed to define LBD-specific tau biomarker profiles.

Everyday task knowledge and everyday function in dementia.

Tests of everyday action semantics were developed and piloted in a group of healthy adults (n = 53) and then administered to individuals with Alzheimer's disease (AD; n = 17) or Parkinson's disease dementia (PDD; n = 20). Relations between everyday action knowledge and everyday function were explored. Three action semantic tests were developed: Probe Test - 45 forced-choice questions regarding task sequences, objects, and steps; Picture Sequencing Test - sequential ordering of 4-5 cards depicting task steps; Script Test - open-ended verbal description of the steps required to complete everyday tasks. Cognitive tests, informant reports of functioning, and the Naturalistic Action Test (NAT), a performance-based test of function, also were administered to AD and PDD participants. NAT performance was scored for omission (failure to complete steps) and commission (inaccurate performance of step) errors. The AD and PDD groups performed worse than healthy participants on all action semantic tasks. AD and PDD groups significantly differed on only the Script Test - AD participants generated fewer correct steps. Performance on each of the action semantic tests significantly correlated with NAT omission errors. Only the Sequencing Test significantly predicted omissions, commissions, and informant report of everyday functioning. In sum, task knowledge is associated with omissions in everyday tasks and is impaired in both AD and PDD. The ability to accurately sequence task steps is associated with multiple aspects of everyday function and may be easily assessed with picture arrangement.

The Virtual Kitchen Challenge: preliminary data from a novel virtual reality test of mild difficulties in everyday functioning.

Background: Efficient, objective measures of mild functional difficulties are lacking. Preliminary data from a novel, non-immersive virtual reality, performance-based task (Virtual Kitchen Challenge; VKC) were obtained to address this gap. Methods: 14 older and 21 younger adults completed cognitive tests and two everyday tasks (breakfast, lunch) in the VKC with virtual objects and a touch-screen and in the Real Kitchen with real objects (order counterbalanced). Automated performance measures were obtained from the VKC program and human coders scored VKC and Real Kitchen videos for errors. Results: Older adults made more errors than younger adults on the VKC and Real Kitchen, with similar error patterns across measures. VKC automated measures were significantly related to measures from human coders, performance on the Real Kitchen, and cognitive test scores. Conclusion: The VKC is a valid and highly efficient performance-based measure of subtle functional difficulties with great potential for future clinical and research applications.