Aims Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer’s disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. Methods We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-μm-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases. Results In Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN. Conclusions LC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.

Clarifying the relationships between neuropsychiatric symptoms and Alzheimer's disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate the odds of developing neuropsychiatric symptoms across increasing burdens of neurofibrillary tangle and amyloid-β pathology. Participants who passed away between 2004 and 2014 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies from the Faculty of Medicine at the University of São Paulo. Postmortem interviews with reliable informants were used to collect information regarding neuropsychiatric and cognitive status. Of 1,092 cases collected, those with any non-Alzheimer pathology were excluded, bringing the cohort to 455 cases. Braak staging was used to evaluate neurofibrillary tangle burden, and the CERAD neuropathology score was used to evaluate amyloid-β burden. The 12-item neuropsychiatric inventory was used to evaluate neuropsychiatric symptoms and CDR-SOB score was used to evaluate dementia status. In Braak I/II, significantly increased odds were detected for agitation, anxiety, appetite changes, depression, and sleep disturbances, compared to controls. Increased odds of agitation continue into Braak III/IV. Braak V/VI is associated with higher odds for delusions. No increased odds for neuropsychiatric symptoms were found to correlate with amyloid-β pathology. Increased odds of neuropsychiatric symptoms are associated with early neurofibrillary tangle pathology, suggesting that subcortical neurofibrillary tangle accumulation with minimal cortical pathology is sufficient to impact quality of life and that neuropsychiatric symptoms are a manifestation of AD biological processes.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC‐CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence‐based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

Background Macrophages and T lymphocytes in the perivascular adipose tissue (Pv AT ) were previously linked to coronary artery disease. However, the role of these cells and B lymphocytes in the human Pv AT adjacent to unstable atherosclerotic plaques has not been investigated. Moreover, previous studies were inconclusive on whether Pv AT inflammation was restricted to the surroundings of the atheroma plaque. Methods and Results Coronary arteries were freshly dissected with the surrounding Pv AT . Atherosclerotic plaques were classified according to the internationally accepted anatomopathological criteria. Immune cells in the Pv AT were detected using immunohistochemistry and then quantified. We used linear and logistic regressions with robust standard errors, adjusted for possible confounding factors. In 246 atherosclerotic plaques (205 stable and 41 unstable plaques) from 82 participants (mean age=69.0±14.4 years; 50% men), the percentage of arterial obstruction was positively correlated with the densities of CD 68 + macrophages ( P =0.003) and CD 20 + B lymphocytes ( P =0.03) in the periplaque Pv AT . The number of cells was greater in the periplaque Pv AT than in the distal Pv AT (macrophages, P <0.001; B lymphocytes, P =0.04). In addition, the density of macrophages in the periplaque Pv AT was greater in the presence of unstable plaques ( P =0.03) and was also greater near unstable plaques than in the distal Pv AT ( P =0.001). CD 3 + T lymphocytes were not associated with percentage of obstruction and stable/unstable plaque composition. Conclusions The density of CD 20 + B lymphocytes and CD 68 + macrophages in periplaque Pv AT was increased with plaque size, and the CD 68 + macrophages were greater near unstable atherosclerotic plaques than near stable lesions. This inflammation was more intense in the periplaque Pv AT than in the Pv AT distal to the atherosclerotic plaques.

Background Behavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation. Objective To compare the prevalence of BPSD according to cognitive status, and to determine NPI cutoffs that best discern individuals with mild cognitive impairment (MCI) and dementia from those without dementia. Methods We included 1,565 participants (mean age = 72.7 ± 12.2 years, 48% male). BPSD and cognitive status were assessed with the NPI and the Clinical Dementia Rating (CDR). We used multivariable logistic regression models to investigate the association of BPSD with cognitive status. The area under the curve (AUC) was used to assess model discrimination, and to determine the best NPI cutoff for MCI and dementia. Results Participants were cognitively normal (CDR = 0; n = 1,062), MCI (CDR = 0.5; n = 145), or dementia (CDR ≥ 1.0, n = 358). NPI symptoms were more frequent in dementia and MCI when compared to cognitively normal. Higher odds for delusions, hallucinations, disinhibition, and psychomotor alterations were found among participants with dementia and MCI than in those who were cognitively normal. The best NPI cutoff to discern participants with dementia from those cognitively normal was 11 (AUC = 0.755). Poor discrimination (AUC = 0.563) was found for the comparison of MCI and those cognitively normal. Conclusions We found an increase in BPSD frequencies across the continuum of cognitive impairment. BPSD severity and frequency in MCI was more similar to individuals cognitively normal than with dementia. NPI scores ≥ to 11 in individuals with no diagnosis of dementia can support the decision for further investigation of dementia.

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.

OBJECTIVE Verify if aging is an independent predictor of NW in ICU, according to age groups, and its predictive value as a determinant of NW in ICU. METHODS Study was conducted from 2012 to 2016. A convenience sample composed by patients (age ≥ 18) admitted to nine ICU belonging to a Brazilian hospital, was analyzed. Age was assumed as an independent variable and NW (measured by the Nursing Activities Score - NAS) as dependent. Linear regression model and ROC curve were used for the analysis. RESULTS 890 participants (361 older people), mostly males (58.1%). The mean NAS score was higher among older participants in comparison to adults (p=0.004) but not within categories of aging (p=0.697). Age was responsible for 0.6% of NAS score. Each year of age increases NAS score in 0.081 points (p=0.015). However, age was not a good predictor of NAS score (AUC = 0.394; p=0.320). CONCLUSION The care of older people in ICU is associated with an increase in NW, compared to adults. Aging can be considered an associated factor but not a good predictor of NW in ICU.

Objective: To characterize the level of acuity, severity and intensity of care of adults and older adults admitted to Intensive Care Units and to identify the predictors of severity with their respective predictive capacity according to the age group. Method: A retrospective cohort based on the analysis of medical records of individuals admitted to eight adult intensive care units in the city of São Paulo. The clinical characteristics at admission in relation to severity profile and intensity of care were analyzed through association and correlation tests. The predictors were identified by linear regression and the predictive capacity through the ROC curve. Results: Of the 781 cases (41.1% from older adults), 56.2% were males with a mean age of 54.1 ± 17.3 years. The burden of the disease, the organic dysfunction and the number of devices were the predictors associated with greater severity among adults and older adults, in which the organic dysfunction had the highest predictive capacity (80%) in both groups. Conclusion: Adults and older adults presented a similar profile of severity and intensity of care in admission to the Intensive Care Unit. Organic dysfunction was the factor with the best ability to predict severity in adults and older adults.