Impact of dementia care training on nurse care managers' interactions with family caregivers.

BACKGROUND: Nurse care managers (NCM) operate through care management programs to provide care for persons living with dementia (PLWD) and interact regularly with their family caregivers; however, most do not receive formal instruction in dementia care or caregiver support. CRESCENT (CaReEcoSystem primary Care Embedded demeNtia Treatment) is a telephone-based dementia care intervention adapted from the Care EcoSystem model designed to equip NCMs with these tools. For this study, we aimed to measure intervention fidelity and understand how dementia care training impacted NCMs' provision of dementia care management services during interactions with caregivers of PLWD. METHODS: We recruited 30 active NCMs; 15 were randomly assigned to receive training. For each nurse, we randomly selected 1-3 patients with a diagnosis of dementia in each nurse's care during January-June 2021 for a total of 54 medical charts. To assess training uptake and fidelity, we identified documentation by NCMs of CRESCENT protocol implementation in the medical records. To understand how the training impacted the amount and types of dementia care management services provided in interactions with family caregivers, we compared attention to key dementia topic areas between trained NCMs (intervention) and untrained NCMs (control). RESULTS: Within the trained group only, community resources for PLWD, followed by safety, medication reconciliation, and advanced care planning topic areas were addressed most frequently (> 30%), while behavior management was addressed least frequently (12%). Trained NCMs were more likely to document addressing aspects of caregiver wellbeing (p = 0.03), community resources (p = 0.002), and identification of behavior (p = 0.03) and safety issues (p = 0.02) compared to those without training. There was no difference between groups in the amount of care coordination provided (p = 0.64). CONCLUSION: Results from this study demonstrate that focused dementia care training enriches care conversations in important topic areas for PLWD and family caregivers. Future research will clarify how best to sustain and optimize high quality dementia care in care management programs with special attention to the NCM-family caregiver relationship. TRIAL NUMBER: NCT04556097.

Multimodal neuroimaging of sex differences in cognitively impaired patients on the Alzheimer's continuum: greater tau-PET retention in females.

We assessed sex differences in amyloid- and tau-PET retention in 119 amyloid positive patients with mild cognitive impairment or Alzheimer's disease (AD) dementia. Patients underwent 3T-MRI, 11C-PIB amyloid-PET and 18F-Flortaucipir tau-PET. Linear ordinary least squares regression models tested sex differences in Flortaucipir-PET SUVR in a summary temporal region of interest as well as global PIB-PET. No sex differences were observed in demographics, Clinical Dementia Rating Sum of Boxes (CDR-SoB), Mini-Mental State Exam (MMSE), raw episodic memory scores, or cortical thickness. Females had higher global PIB SUVR (ηp²=.043, p=.025) and temporal Flortaucipir SUVR (ηp²=.070, p=.004), adjusting for age and CDR-SoB. Sex differences in temporal Flortaucipir-PET remained significant when controlling additionally for PIB SUVR and APOE4 status (ηp²=.055, p=.013), or when using partial volume-corrected data. No sex differences were present in areas of known Flortaucipir off-target binding. Overall, females demonstrated greater AD regional tau-PET burden than males despite clinical comparability. Further characterization of sex differences will provide insight into AD pathogenesis and support development of personalized therapeutic strategies.

Crossed cerebellar diaschisis on 18F-FDG PET: Frequency across neurodegenerative syndromes and association with 11C-PIB and 18F-Flortaucipir.

We used 18F-FDG-PET to investigate the frequency of crossed cerebellar diaschisis (CCD) in 197 patients with various syndromes associated with neurodegenerative diseases. In a subset of 117 patients, we studied relationships between CCD and cortical asymmetry of Alzheimer's pathology (ß-amyloid (11C-PIB) and tau (18F-Flortaucipir)). PET images were processed using MRIs to derive parametric SUVR images and define regions of interest. Indices of asymmetry were calculated in the cerebral cortex, basal ganglia and cerebellar cortex. Across all patients, cerebellar 18F-FDG asymmetry was associated with reverse asymmetry of 18F-FDG in the cerebral cortex (especially frontal and parietal areas) and basal ganglia. Based on our operational definition (cerebellar asymmetry >3% with contralateral supratentorial hypometabolism), significant CCD was present in 47/197 (24%) patients and was most frequent in corticobasal syndrome and semantic and logopenic variants of primary progressive aphasia. In ß-amyloid-positive patients, mediation analyses showed that 18F-Flortaucipir cortical asymmetry was associated with cerebellar 18F-FDG asymmetry, but that cortical 18F-FDG asymmetry mediated this relationship. Analysis of 18F-FDG-SUVR values suggested that CCD might also occur in the absence of frank cerebellar 18F-FDG asymmetry due to symmetrical supratentorial degeneration resulting in a bilateral diaschisis process.

Comparing ATN-T designation by tau PET visual reads, tau PET quantification, and CSF PTau181 across three cohorts.

PURPOSE: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer's Disease (AD) Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). METHODS: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from (1) FTP visual assessment by two blinded raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥1.27); and (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/mL). RESULTS: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T-status between modality pairs ranged from 68 to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aß + MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was most sensitive (0.96) but least specific (0.60). Specificity was highest with FTP SUVR (0.91) with sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. CONCLUSION: The choice of tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages.

Tau Positron Emission Tomographic Findings in a Former US Football Player With Pathologically Confirmed Chronic Traumatic Encephalopathy.

Importance: Biomarkers for chronic traumatic encephalopathy (CTE) are currently lacking. The radiotracer fluorine F 18-labeled (18F)-flortaucipir (FTP) detects tau pathology in Alzheimer disease, and positron emission tomography (PET) with FTP shows elevated binding in individuals at risk for CTE. No study, however, has assessed the correlation between in vivo FTP PET and postmortem tau in CTE. Objective: To assess the regional association between in vivo FTP binding and postmortem tau pathology in a patient with pathologically confirmed CTE. Design, Setting, and Participants: A white male former National Football League player with 17 years of US football exposure was clinically diagnosed with traumatic encephalopathy syndrome at a neurology tertiary referral center. 18F-Fludeoxyglucose, carbon 11-labeled Pittsburgh compound B, and FTP PET were performed 52 months prior to death, and magnetic resonance imaging, 50 months prior to death. Brain images were assessed qualitatively for abnormalities blinded to autopsy data. Autopsy was performed using a neurodegenerative research protocol. The FTP standardized uptake value ratios (inferior cerebellar gray reference region) and W-score (age-adjusted z-score) maps were compared with phosphorylated tau immunohistochemical analysis with monoclonal antibody CP13. Main Outcomes and Measures: Qualitative and quantitative comparisons between antemortem FTP PET and tau pathology at autopsy. Results: Flortaucipir uptake was distributed in a patchy, frontotemporal-predominant pattern that overlapped with regions showing neurodegeneration on magnetic resonance imaging and hypometabolism on 18F-fludeoxyglucose PET. Pathological assessment revealed stage 4 CTE; limbic argyrophilic grain disease; stage 2 limbic-predominant, age-related transactive response DNA-binding protein 43 encephalopathy; and Braak neurofibrillary tangle stage 3. 18F-Flortaucipir W-maps matched areas of high postmortem tau burden in left fusiform and inferior temporal gyri and juxtacortical frontal white matter. High FTP W-scores with low tau burden were found in the basal ganglia, thalamus, motor cortex, and calcarine cortex. No regions with low FTP W-scores corresponded to areas with high pathological tau burden. A modest correlation, which did not reach statistical significance (ρ = 0.35, P = .17), was found between FTP standardized uptake value ratio and tau area fraction at the regional level. Conclusions and Relevance: In this patient, FTP PET findings during life showed a modest correspondence with postmortem pathology in CTE. These findings suggest that FTP may have limited utility as a tau biomarker in CTE.

Longitudinal tau accumulation and atrophy in aging and alzheimer disease.

OBJECTIVE: To determine the rate of tau accumulation in healthy older adults (OA) and patients with Alzheimer disease (AD), as well as the relationship of tau accumulation to cortical atrophy. METHODS: Two longitudinal flortaucipir (FTP) positron emission tomography (PET) and magnetic resonance imaging (MRI) scans were acquired from 42 OA (21 Pittsburg compound B [PiB]+ , age = 77.6 ± 4.6 years, 25 female [F]/17 male [M]) and 19 PiB+ patients with AD (age = 63.1 ± 10.3 years, 12 F/7 M) over 1 to 3 years of follow-up. FTP change, structural MRI measures of atrophy, and cross-modal correlations were examined on a voxelwise level. Regional annual percentage change in FTP was also calculated. RESULTS: Voxelwise FTP change in AD showed the greatest increases in lateral and medial frontal lobes. Atrophy over the same interval was more widespread and included posteromedial cortical areas, where tau accumulation rates were lower. In OA, FTP binding increased in bilateral temporal lobe and retrosplenial cortex, accompanied by atrophy in the same regions. There were no associations between voxelwise change in FTP and sex, PiB, or APOE. Regional FTP significantly increased at follow-up in OA and patients with AD. Mixed effects models showed greater FTP increases in AD compared to OA, and no differences within OA based on PiB status. INTERPRETATION: Our findings indicate that tau accumulates even in amyloid-negative healthy OA and this process can be measured with in vivo tau-PET. In OA, tau accumulation and atrophy share a similar topography. In AD, tau increases more rapidly and accumulation occurs in frontal regions that are not yet undergoing significant atrophy. Ann Neurol 2019; 1-12 ANN NEUROL 2019;85:229-240.

Amyloid and tau PET demonstrate region-specific associations in normal older people.

ß-amyloid (Aß) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [18F]AV-1451 (for tau) and [11C]PiB (for Aß) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant's mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB-AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p<.01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aß and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aß and tau accumulation does not appear to be specific to Aß location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aß accumulates.