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Disinhibition is one of the most distressing and difficult to treat neuropsychiatric symptoms of dementia. It involves socially inappropriate behaviours, such as hypersexual comments, inappropriate approaching of strangers and excessive jocularity. Disinhibition occurs in multiple dementia syndromes, including behavioural variant frontotemporal dementia, and dementia of the Alzheimers type. Morphometric similarity networks are a relatively new method for examining brain structure and can be used to calculate measures of network integrity on large scale brain networks and subnetworks such as the salience network and cognitive control network. In a cross-sectional study, we calculated morphometric similarity networks to determine whether disinhibition in behavioural variant frontotemporal dementia (n = 75) and dementia of the Alzheimers type (n = 111) was associated with reduced integrity of these networks independent of diagnosis. We found that presence of disinhibition, measured by the Neuropsychiatric Inventory Questionnaire, was associated with reduced global efficiency of the cognitive control network in both dementia of the Alzheimers type and behavioural variant frontotemporal dementia. Future research should replicate this transdiagnostic finding in other dementia diagnoses and imaging modalities, and investigate the potential for intervention at the level of the cognitive control network to target disinhibition.

Introduction: Frontotemporal lobar degeneration (FTLD) is associated with FTLD due to tau (FTLD-tau) or TDP (FTLD-TDP) inclusions found at autopsy. Arterial Spin Labeling (ASL) MRI is often acquired in the same session as a structural T1- weighted image (T1w), enabling detection of regional changes in cerebral blood flow (CBF). We hypothesize that ASL-T1w registration with more degrees of freedom using boundary-based registration (BBR) will better align ASL and T1w images and show increased sensitivity to regional hypoperfusion differences compared to manual registration in patient participants. We hypothesize that hypoperfusion will be associated with a clinical measure of disease severity, the FTLD-modified clinical dementia rating scale sum-of-boxes (FTLD-CDR). Materials and methods: Patients with sporadic likely FTLD-tau (sFTLD-tau; N = 21), with sporadic likely FTLD-TDP (sFTLD-TDP; N = 14), and controls (N = 50) were recruited from the Connectomic Imaging in Familial and Sporadic Frontotemporal Degeneration project (FTDHCP). Pearson's Correlation Coefficients (CC) were calculated on cortical vertex-wise CBF between each participant for each of 3 registration methods: (1) manual registration, (2) BBR initialized with manual registration (manual+BBR), (3) and BBR initialized using FLIRT (FLIRT+BBR). Mean CBF was calculated in the same regions of interest (ROIs) for each registration method after image alignment. Paired t-tests of CC values for each registration method were performed to compare alignment. Mean CBF in each ROI was compared between groups using t-tests. Differences were considered significant at p < 0.05 (Bonferroni-corrected). We performed linear regression to relate FTLD-CDR to mean CBF in patients with sFTLD-tau and sFTLD-TDP, separately (p < 0.05, uncorrected). Results: All registration methods demonstrated significant hypoperfusion in frontal and temporal regions in each patient group relative to controls. All registration methods detected hypoperfusion in the left insular cortex, middle temporal gyrus, and temporal pole in sFTLD-TDP relative to sFTLD-tau. FTLD- CDR had an inverse association with CBF in right temporal and orbitofrontal ROIs in sFTLD-TDP. Manual+BBR performed similarly to FLIRT+BBR. Discussion: ASL is sensitive to distinct regions of hypoperfusion in patient participants relative to controls, and in patients with sFTLD-TDP relative to sFTLD-tau, and decreasing perfusion is associated with increasing disease severity, at least in sFTLD-TDP. BBR can register ASL-T1w images adequately for controls and patients. [ABSTRACT FROM AUTHOR]

Objective The percentage of older adults living into their 80s and beyond is expanding rapidly. Characterization of typical cognitive performance in this population is complicated by a dearth of normative data for the oldest old. Additionally, little attention has been paid to other aspects of health, such as motor, sensory, and emotional functioning, that may interact with cognitive changes to predict quality of life and well-being. The current study used the NIH Toolbox (NIHTB) to determine age group differences between persons aged 65–84 and 85+ with normal cognition. Method Participants were recruited in two age bands (i.e. 65–84 and 85+). All participants completed the NIHTB Cognition, Motor, Sensation, and Emotion modules. Independent-samples t -tests determined age group differences with post-hoc adjustments using Bonferroni corrections. All subtest and composite scores were then regressed on age and other demographic covariates. Results The 65–84 group obtained significantly higher scores than the 85+ group across all cognitive measures except oral reading, all motor measures except gait speed, and all sensation measures except pain interference. Age remained a significant predictor after controlling for covariates. Age was not significantly associated with differences in emotion scores. Conclusions Results support the use of the NIHTB in persons over 85 with normal cognition. As expected, fluid reasoning abilities and certain motor and sensory functions decreased with age in the oldest old. Inclusion of motor and sensation batteries is warranted when studying trajectories of aging in the oldest old to allow for multidimensional characterization of health. [ABSTRACT FROM AUTHOR]

Pick's disease (PiD) is a subtype of the tauopathy form of frontotemporal lobar degeneration (FTLD-tau) characterized by intraneuronal 3R-tau inclusions. PiD can underly various dementia syndromes, including primary progressive aphasia (PPA), characterized by an isolated and progressive impairment of language and left-predominant atrophy, and behavioral variant frontotemporal dementia (bvFTD), characterized by progressive dysfunction in personality and bilateral frontotemporal atrophy. In this study, we investigated the neocortical and hippocampal distributions of Pick bodies in bvFTD and PPA to establish clinicopathologic concordance between PiD and the salience of the aphasic versus behavioral phenotype. Eighteen right-handed cases with PiD as the primary pathologic diagnosis were identified from the Northwestern University Alzheimer's Disease Research Center brain bank (bvFTD, N = 9; PPA, N = 9). Paraffin-embedded sections were stained immunohistochemically with AT8 to visualize Pick bodies, and unbiased stereological analysis was performed in up to six regions bilaterally [middle frontal gyrus (MFG), superior temporal gyrus (STG), inferior parietal lobule (IPL), anterior temporal lobe (ATL), dentate gyrus (DG) and CA1 of the hippocampus], and unilateral occipital cortex (OCC). In bvFTD, peak neocortical densities of Pick bodies were in the MFG, while the ATL was the most affected in PPA. Both the IPL and STG had greater leftward pathology in PPA, with the latter reaching significance (p < 0.01). In bvFTD, Pick body densities were significantly right-asymmetric in the STG (p < 0.05). Hippocampal burden was not clinicopathologically concordant, as both bvFTD and PPA cases demonstrated significant hippocampal pathology compared to neocortical densities (p < 0.0001). Inclusion-to-neuron analyses in a subset of PPA cases confirmed that neurons in the DG are disproportionately burdened with inclusions compared to neocortical areas. Overall, stereological quantitation suggests that the distribution of neocortical Pick body pathology is concordant with salient clinical features unique to PPA vs. bvFTD while raising intriguing questions about the selective vulnerability of the hippocampus to 3R-tauopathies. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions With changing cognitive abilities, individuals with mild cognitive impairment (MCI) and dementia face challenges in successfully managing multidrug regimens. We sought to understand how individuals with MCI or dementia and their family caregivers manage multidrug regimens and better understand patient‐to‐caregiver transitions in medication management responsibilities.We conducted qualitative interviews among patient–caregiver dyads. Eligibility included: patients with a diagnosis of MCI, mild or moderate dementia, managing ≥3 chronic conditions, ≥5 prescription medications, who also had a family caregiver ≥18 years old. Semi‐structured interview guides, informed by the Medication Self‐Management model, ascertained roles and responsibilities for medication management and patient‐to‐caregiver transitions in medication responsibilities.We interviewed 32 patient–caregiver dyads. Older adults and caregivers favored older adult autonomy in medication management, and individuals with MCI and mild dementia largely managed their medications independently using multiple strategies (e.g., establishing daily routines, using pillboxes). Among individuals with moderate dementia, caregivers assumed all medication‐related responsibilities except when living separately. In those scenarios, caregivers set up organizers and made reminder calls, but did not observe family members taking medications. Patient‐to‐caregiver transitions in medication responsibilities frequently occurred after caregivers observed older adults making errors with medications. As caregivers sought to assume greater responsibilities with family members' medicines, they faced multiple barriers. Most barriers were dyadic; they affected both the older adult and the caregiver and/or the relationship. Some barriers were specific to caregivers; these included caregivers' competing responsibilities or inaccurate perceptions of dementia, while other barriers were related to the healthcare system.To ease medication management transitions, balance must be sought between preservation of older adult autonomy and early family caregiver involvement. Clinicians should work to initiate conversations with family caregivers and individuals living with MCI or dementia about transitioning medication responsibilities as memory loss progresses, simplify regimens, and deprescribe, as appropriate. [ABSTRACT FROM AUTHOR]

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults., Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3., Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease., Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board., Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion., Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources)., Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.