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Sarcopenia is characterized as aging-related weakness and atrophy, which decreases the diaphragm force generating capacity leading to a decrease of expulsive non-ventilatory motor behaviors, which are critical for airway clearance. Thus, this study aimed to analyze the histopathology of the diaphragm in postmortem samples. Thirty individuals were included. Diaphragm samples were stained with hematoxylin and eosin for histopathological analysis. Picrosirius stain was used to highlight the collagen fibers. We observed a positive association between advancing age and histopathological findings in the diaphragm structure. We suggest that age is a key factor in increasing diaphragm muscle histopathology. However, further clinicopathological studies are needed to confirm our findings., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Neurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

Objective: To evaluate elderly patients in a geriatric service, along with their sensory characteristics and their association with clinical aspects., Methods: This was a descriptive longitudinal study. We enrolled 36 healthy participants of both sexes in this study. The following instruments were used and evaluations performed: clinical evaluation, Mini-Mental State Exam, and quantitative sensory testing., Results: During the follow-up, there was reduction of mean corpuscular volume at each evaluation (p < 0.001) and significant increase in mean corpuscular hemoglobin concentration (p < 0.001). There was an increase of the olfactory (p < 0.001), salty (p = 0.024), sour (p = 0.020), bitter (p = 0.001), facial cold (p = 0.019), hand cold (p = 0.004), facial tactile (p < 0.001), hand tactile (p = 0.012) and facial vibration (p = 0.018) thresholds. Previous existing morbidities were associated with sensitivity changes in the individuals in this sample., Conclusion: This longitudinal study suggests that the loss of sensitivity with aging may be associated with the presence of morbidities in elders.

The normal hematological values in various phases of the rat life provide a valuable guide to researchers and could be useful for experimental works. However, database information available on the literature are incomplete., Aim: This study aimed to present normal hematological parameters of young and aged rats., Methods: Male and female rats were distributed into seven experimental groups with 1, 2, 3, 6, 12, 18, and 24 months of age. Blood samples taken from the tails were analyzed. Normal hematological values were determined for each age group., Results: Rats showed a progressive weight gain with advancing age, predominantly after 3 months of life. With advancing age, differences were found on hematological parameters: some of them showed a progressive rise with age and others did not. Hemoglobin levels and hematocrit did not change while the number of circulating red blood cells suffered slight increase., Conclusion: The present study determined the normal values for absolute and relative hematological parameters in Wistar rats from 2 to 24 months for male and female rats. The results can be used in studies of effects of aging, feeding, and medications on growing and aging rats.

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.

Background: Despite the well-known declines in driving performance with advancing age, there is little understanding of the specific factors that predict changes in key determinants such as braking time., Objectives: The aims of this study were to determine the extent to which age, muscle strength, cognition and postural balance are associated with braking performance in middle-aged and older adults., Methods: Male and female middle-aged adults (n=62, age=39.3±7.1years) and older adults (n=102, age=70.4±5.8years) were evaluated for braking performance, as well as in several motor and cognitive performance tasks. The motor evaluation included isokinetic ankle plantar flexor muscle strength, handgrip strength, and postural balance with and without a cognitive task. The cognitive assessment included the Mini Mental State Examination. Braking performance was measured using a driving simulator., Results: Older adults exhibited 17% slower braking time, lower strength, and poorer performance in the postural balance (p<0.001). For both older and middle-aged adults, significant correlates of braking time included performance in the postural balance tests, muscle strength, and cognitive function. However, after full model adjustment, only postural balance and cognitive function were significantly associated., Conclusion: Muscle strength, postural balance, and cognition are associated with braking time, and may affect the safety of and driving performance in older adults. These findings may help to inform specific targeted interventions that could preserve driving performance during aging., (Copyright © 2016 Elsevier Inc. All rights reserved.)

What is the influence of sex and age on the quantitative cell composition of the human brain? By using the isotropic fractionator to estimate absolute cell numbers in selected brain regions, we looked for sex- and age-related differences in 32 medial temporal lobes (comprised basically by the hippocampal formation, amygdala and parahippocampal gyrus), sixteen male (29-92 years) and sixteen female (25-82); and 31 cerebella, seventeen male (29-92 years) and fourteen female (25-82). These regions were dissected from the brain, fixed and homogenized, and then labeled with a DNA-marker (to count all nuclei) and with a neuron-specific nuclear marker (to estimate neuron number). Total number of cells in the medial temporal lobe was found to be 1.91 billion in men, and 1.47 billion in women, a difference of 23 %. This region showed 34 % more neurons in men than in women: 525.1 million against 347.4 million. In contrast, no sex differences were found in the cerebellum. Regarding the influence of age, a quadratic correlation was found between neuronal numbers and age in the female medial temporal lobe, suggesting an early increase followed by slight decline after age 50. The cerebellum showed numerical stability along aging for both neurons and non-neuronal cells. In sum, results indicate a sex-related regional difference in total and neuronal cell numbers in the medial temporal lobe, but not in the cerebellum. On the other hand, aging was found to impact on cell numbers in the medial temporal lobe, while the cerebellum proved resilient to neuronal losses in the course of life.

The human brain undergoes non-uniform changes during aging. The substantia nigra (SN), the source of major dopaminergic pathways in the brain, is particularly vulnerable to changes in the progression of several age-related neurodegenerative diseases. To establish normative data for high-resolution imaging, and to further clinical and anatomical studies we analyzed SNs from 15 subjects aged 50-91 cognitively normal human subjects without signs of parkinsonism. Complete brains or brainstems with substantia nigra were formalin-fixed, celloidin-mounted, serially cut and Nissl-stained. The shapes of all SNs investigated were reconstructed using fast, high-resolution computer-assisted 3D reconstruction software. We found a negative correlation between age and SN volume (p = 0.04, rho = -0.53), with great variability in neuronal numbers and density across participants. The 3D reconstructions revealed SN inter- and intra-individual variability. Furthermore, we observed that human SN is a neuronal reticulum, rather than a group of isolated neuronal islands. Caution is required when using SN volume as a surrogate for SN status in individual subjects. The use of multimodal sequences including those for fiber tracts may enhance the value of imaging as a diagnostic tool to assess SN in vivo. Further studies with a larger sample size are needed for understanding the structure-function interaction of human SN., Competing Interests: The authors declare that there are no conflicts of interest.

Purpose: To report lung parenchymal findings on high-resolution computed tomography (HRCT) in a population of asymptomatic, never-smoker urban dwellers aged 65 years and older., Materials and Methods: After institutional approval, asymptomatic older patients from the Geriatrics Outpatient Clinic aged 65 years and older (older group) and healthy volunteers aged 30-50 years (younger group) were invited to participate in the study. Asymptomatic, never-smoker subjects considered free of relevant disease after spirometry and echocardiography underwent chest HRCT. Three researchers reviewed every scan, noting the absence/presence and distribution of pre-specified parenchymal findings. Statistical comparisons between groups were performed using appropriate tests with the aid of software., Results: Forty-seven older and 24 younger subjects were included in this analysis. A higher proportion of women and a longer history of urban dwelling were present in the older group. Parenchymal findings were more prevalent in the older group (78.7 vs. 25% in the younger group; p < 0.001). Parenchymal bands (59.6 vs. 25%; p = 0.007), ground-glass opacities (25.5 vs. 0%; p = 0.006), and septal lines (21.3 vs. 0%; p = 0.013) were more prevalent in the elderly. When only subjects aged 75 years and older were considered as the older group, micronodules, reticular opacities, cysts, and bronchiectases (19.1 vs. 0 % for all comparisons; p = 0.04) were also more frequently found among the elderly., Conclusion: Parenchymal bands, ground-glass opacities, septal lines, bronchiectasis, micronodules, reticular opacities, and lung cysts were more prevalent among the elderly.

Background: We showed previously that nasal mucociliary clearance was decreased in critically ill elderly subjects, most of whom had diabetes mellitus (DM) and/or hypertension (HTN). To determine if these changes were due to the effects of aging, disease, or critical illness, we studied nasal mucociliary clearance and mucus properties in an ambulatory population consisting of young, elderly, and healthy subjects and those with DM, HTN, or both., Methods: Of 440 subjects contacted, 252 entered the study. The subjects were divided into the following groups: (1) healthy (n 5 79, 18-94 years, 50 men) and (2) DM and/or HTN, of which 37 had DM (14-90 years, 12 men), 52 had HTN (23-90 years, 12 men), and 84 had both DM and HTN (25-82 years, 33 men). Subjects were also grouped by age: , 40 years, 40 to 59 years, and 60 years. We assessed demographic and clinical data, quality of life using the 36-Item Short Form Health Survey (SF-36) questionnaire, nasal mucociliary clearance using the saccharine transit test (STT), and in vitro mucus properties by examining the sneeze (high airflow) clearability and contact angle. A logistic regression analysis for prolonged STT . 12 min was used, and we controlled for age, sex, and diseases., Results: Subjects aged . 60 years reported a decreased SF-36 physical component relative to other age groups. Sex, BMI, BP, heart rate, pulse oximetry, blood glucose level, and mucus properties were not associated with prolonged STT. Aging and DM and/or HTN independently increased the risk of prolonged STT., Conclusions: Aging and DM, HTN, or both diseases are independently associated with decreased nasal mucociliary clearance. This may predispose toward respiratory infections.

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in womens frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has ~10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE ε4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE ε4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE ε4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE ε4 risk compared to European ancestry.

ObjectiveThis study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias.MethodsWe analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia.ResultsIn a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P=0.023), AD+VaD (P=0.046), and DLB (P=0.043) groups. In addition, VaD (P=0.041) and AD+VaD (P=0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy.ConclusionOur findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.

ObjectiveTo establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining.MethodsIn autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables.ResultsIn our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3).ConclusionHead circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.

The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age-related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age-associated neurodegenerative diseases, but little is known about whether this process also occurs in physiological aging, as well as its functional implication. Here, we investigated astrocyte senescence in vitro, in old mouse brains, and in post-mortem human brain tissue of elderly. We identified a significant loss of lamin-B1, a major component of the nuclear lamina, as a hallmark of senescent astrocytes. We showed a severe reduction of lamin-B1 in the dentate gyrus of aged mice, including in hippocampal astrocytes, and in the granular cell layer of the hippocampus of post-mortem human tissue from non-demented elderly. The lamin-B1 reduction was associated with nuclear deformations, represented by an increased incidence of invaginated nuclei and loss of nuclear circularity in senescent astrocytes in vitro and in the aging human hippocampus. We also found differences in lamin-B1 levels and astrocyte nuclear morphology between the granular cell layer and polymorphic layer in the elderly human hippocampus, suggesting an intra-regional-dependent aging response of human astrocytes. Moreover, we described senescence-associated impaired neuritogenic and synaptogenic capacity of mouse astrocytes. Our findings show that reduction of lamin-B1 is a conserved feature of hippocampal cells aging, including astrocytes, and shed light on significant defects in nuclear lamina structure which may contribute to astrocyte dysfunctions during aging.

The choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging and in various diseases of the central nervous system, including Alzheimer's disease. In the present study, a high-throughput sequencing of the CP transcriptome was performed in postmortem samples of clinically healthy individuals aged 50's through 80's. The data shows an age-related profile, with the main changes occurring in the transition from the 50's to the 60's, stabilizing thereafter. Specifically, neuronal and membrane functions distinguish the transcriptome between the 50's and the 60's, while neuronal and axon development and extracellular structure organization differentiate the 50's from the 70's. These findings suggest that changes in the CP transcriptome occur early in the aging process. Future studies will unravel whether these relate with processes occurring in late- onset brain diseases.

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and dementia in deceased individuals who underwent a full-body autopsy examination. Methods: Weight and height were measured before the autopsy exam. Cognitive function before death was investigated using the Clinical Dementia Rating (CDR) scale. The cross-sectional association between BMI and dementia was investigated using linear regression models adjusted for sociodemographic and clinical variables. Results: We included 1,090 individuals (mean age 69.5 ± 13.5 years old, 46% women). Most participants (56%) had a normal BMI (18.5-24.9 kg/m2), and the prevalence of dementia was 16%. Twenty-four percent of the sample had cancer, including 76 cases diagnosed only by the autopsy examination. Moderate and severe dementia were associated with lower BMI compared with participants with normal cognition in fully adjusted models (moderate: β = -1.92, 95% CI = -3.77 to -0.06, p = 0.042; severe: β = -2.91, 95% CI = -3.97 to -1.86, p < 0.001). Conclusion: BMI was associated with moderate and severe dementia in late life, but we did not find associations of BMI with less advanced dementia stages.

Background Macrophages and T lymphocytes in the perivascular adipose tissue (PvAT) were previously linked to coronary artery disease. However, the role of these cells and B lymphocytes in the human PvAT adjacent to unstable atherosclerotic plaques has not been investigated. Moreover, previous studies were inconclusive on whether PvAT inflammation was restricted to the surroundings of the atheroma plaque. Methods and Results Coronary arteries were freshly dissected with the surrounding PvAT. Atherosclerotic plaques were classified according to the internationally accepted anatomopathological criteria. Immune cells in the PvAT 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 CD68+ macrophages (P=0.003) and CD20+ B lymphocytes (P=0.03) in the periplaque PvAT. The number of cells was greater in the periplaque PvAT than in the distal PvAT (macrophages, P

ObjectiveTo compare neuropathological correlates of cognitive impairment between very old and younger individuals from a Brazilian clinicopathological study.MethodsWe assessed the frequency of neuropathological lesions and their association with cognitive impairment (Clinical Dementia Rating scale ≥0.5) in the 80 or over age group compared to younger participants, using logistic regression models adjusted for sex, race and education.ResultsExcept for infarcts and siderocalcinosis, all neuropathological lesions were more common in the 80 or over age group (n = 412) compared to 50-79 year olds (n = 677). Very old participants had more than twice the likelihood of having ≥2 neuropathological diagnoses than younger participants (OR = 2.66, 95% CI = 2.03-3.50). Neurofibrillary tangles, infarcts and hyaline arteriolosclerosis were associated with cognitive impairment in the two age groups. Siderocalcinosis was associated with cognitive impairment in the younger participants only, while Lewy body disease was associated with cognitive impairment in the very old only. In addition, we found that the association of infarcts and multiple pathologies with cognitive impairment was attenuated in very old adults (Infarcts: P for interaction = 0.04; and multiple pathologies: P = 0.05). However, the predictive value for the aggregate model with all neuropathological lesions showed similar discrimination in both age groups [Area under Receiver Operating Characteristic curve (AUROC) = 0.778 in younger participants and AUROC = 0.765 in the very old].Conclusion and relevanceDespite a higher frequency of neuropathological findings in the very old group, as found in studies with high-income populations, we found attenuation of the effect of infarcts rather than neurofibrillary tangles and plaques as reported previously.

Background: The relationship between cognitive impairment and abdominal visceral is controversial. Moreover, all studies so far used imaging studies to evaluate visceral fat and this association has not been described yet using autopsy material, which allows the direct quantification of abdominal fat. We aimed to investigate the association between direct measurements of abdominal visceral fat and cognitive impairment in an autopsy study. Methods: In this cross-sectional study, we collected information on sociodemographics, cardiovascular risk factors, and cognitive status from subjects aged 50 or older at time of death in a general autopsy service in Brazil. Abdominal visceral fat was obtained in natura by the dissection of perirenal, mesenteric, omental, and mesocolon fat. The associations of total abdominal visceral fat with cognitive impairment [clinical dementia rating (CDR) score ≥0.5] and CDR-sum of boxes (CDR-SB) were evaluated using logistic regression and negative binomial regression models, respectively. All analyses were adjusted for height, age, sex, education, hypertension, diabetes mellitus, stroke, smoking, alcohol use, and physical inactivity. In addition, we compared the discrimination of visceral fat, body mass index (BMI), and waist circumference (WC) measurements in predicting cognitive impairment. Results: We evaluated 234 participants (mean age = 71.2 ± 12.9 years old, 59% male). Abdominal visceral fat was inversely associated with cognitive impairment (OR = 0.46, CI = 0.30; 0.70, p < 0.0001) and with CDR-SB scores (β = -0.85, 95% CI = -1.28; -0.43, p < 0.0001). When we compared the area under the ROC curve (AUC), visceral fat (AUC = 0.754), BMI (AUC = 0.729), and WC (AUC = 0.720) showed similar discrimination in predicting cognitive impairment (p = 0.38). Conclusion: In an autopsy study, larger amount of directly measured abdominal visceral fat was associated with lower odds of cognitive impairment in older adults.

BackgroundBehavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation.ObjectiveTo 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.MethodsWe 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.ResultsParticipants 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.ConclusionsWe 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.

BACKGROUND AND AIMS:Intracranial (IAD) and extracranial atherosclerotic diseases (EAD) have been mostly investigated using imaging methods. Autopsy studies allow for a direct and complete evaluation of the atherosclerotic disease. We aimed to investigate the frequency of IAD and EAD, their association, and related risk profiles in a large cross-sectional autopsy study. METHODS:We measured the intima-media thickness and stenosis of the common (CCA) and internal carotid arteries (ICA), using morphometric measurements. The main outcome was stenosis (≥50%) in the artery with the largest obstruction among the 12 cerebral arteries. We used multivariable logistic regression models to investigate the association between EAD and IAD. RESULTS:In 661 participants (mean age = 71.3 ± 11.7 y, 51% male), stenosis was more common in IAD than in EAD (59% vs. 51%). EAD was associated with Caucasian race, hypertension, and smoking, while IAD was associated with older age, less years of education, hypertension, diabetes, and a previous history of stroke. Stenosis in CCA and ICA was associated with more than two times the odds of having stenosis in the intracranial arteries (CCA: OR = 2.32, 95% CI = 1.64; 3.28; ICA: OR = 2.51, 95% CI = 1.76; 3.57). CONCLUSIONS:In this population-based autopsy study, IAD was common, even more common than EAD, but correlated with EAD.

Clarifying the relationships between neuropsychiatric symptoms and Alzheimers 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.

BackgroundPrevious evidence linking diabetes to Alzheimer's disease (AD) neuropathology is mixed and scant data are available from low- and middle-income countries.ObjectiveTo investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults.MethodsIn this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication. A standardized neuropathological examination was performed using immunohistochemistry. The associations of diabetes with Consortium to Establish and Registry for Alzheimer Disease (CERAD) scores for neuritic plaques and Braak-Braak (BB) scores for neurofibrillary tangles were investigated using multivariable ordinal logistic regression. We investigated effect modification of education, race, and APOE on these associations.ResultsAmong 1,037 subjects (mean age = 74.4±11.5 y; mean education = 4.0±3.7 y; 48% male, 61% White), diabetes was present in 279 subjects. Diabetes was not associated with BB (OR = 1.12, 95% CI = 0.81-1.54, p = 0.48) or with CERAD (OR = 0.97, 95% CI = 0.68-1.38, p = 0.86) scores on analyses adjusted for sociodemographic and clinical variables. We observed effect modification by the APOE allele ɛ4 on the association between diabetes mellitus and BB scores.ConclusionNo evidence of an association between diabetes and AD neuropathology was found in a large sample of Brazilians; however, certain subgroups, such as APOE allele ɛ4 carriers, had higher odds of accumulation of neurofibrillary tangles.

BACKGROUND:Morphometric measurements of systemic atherosclerosis and direct quantification of visceral fat are only possible using materials from autopsy studies. However, the few autopsy studies that have investigated the association of visceral fat with atherosclerosis had small sample sizes and focused on coronary arteries of young or middle-aged White subjects. We aimed to investigate the association of pericardial fat (PF) and abdominal visceral fat (AVF) with atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large autopsy study. MATERIALS AND METHODS:We evaluated deceased subjects aged 30 years or above. We dissected and weighted the PF and the AVF and evaluated the atherosclerotic burden in the aorta, as well as the carotid, coronary, and cerebral arteries using morphometric measurements. We also investigated the interaction of PF and AVF with age regarding the atherosclerotic burden. RESULTS:The mean age of the 240 included subjects was 64.8±15.3 years, and 63% was male. Greater PF was associated with a higher degree of aortic atherosclerosis after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83; 7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not find an association of PF or AVF with carotid or cerebral atherosclerotic burden. We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; -0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04) with age regarding carotid artery atherosclerotic burden. CONCLUSIONS:Greater AVF was associated with greater atherosclerotic burden and extent in coronary arteries, while greater PF correlated with a higher degree of atherosclerosis in the aorta.

BackgroundClinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis.Methods and findingsIn this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20-1.46), IQCODE (β = 0.14, 95% CI 0.13-0.16), and NPI (β = 1.74, 95% CI = 1.33-2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life.ConclusionsNFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.

IntroductionAdiposity has been associated with atherosclerosis in clinical studies. However, few autopsy studies have investigated this association, and they had only examined the coronary artery disease. Moreover, most studies had small sample sizes and were limited to middle-aged or young adults. Our aim is to investigate the association between adiposity and systemic atherosclerosis in an autopsy study.Methods and analysisA sample of 240 deceased with 30 years or more will be evaluated. The sample size was calculated using the lowest correlation coefficient found in previous studies (r=0.109), assuming a power of 90% and α=0.05. We will collect information about sociodemographics, frequency of previous contact of the deceased's next of kin and cardiovascular risk factors. We will measure neck, waist and hip circumferences, weight, height and abdominal subcutaneous tissue thickness, and then we will calculate the body mass index, waist-to-hip ratio, waist-to-height ratio and body shape index. We will also weigh the pericardial and abdominal visceral fat, the heart, and we will measure the left ventricular wall thickness. We will evaluate the presence of myocardial infarction, the degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries and plaque composition in carotid, coronary and cerebral arteries. For each individual, we will fix arterial and adipose tissue samples in 10% formalin and freeze another adipose tissue sample at -80°C for future studies.Ethics and disseminationEthical approval was granted by the Ethics Committee of University of Sao Paulo Medical School, Brazil. Results will be submitted for publication in a peer-reviewed journal.

Argyrophilic grain disease (AGD) is a frequent late-onset, 4-repeat tauopathy reported in Caucasians with high educational attainment. Little is known about AGD in non-Caucasians or in those with low educational attainment. We describe AGD demographics, clinical, and neuropathological features in a multiethnic cohort of 983 subjects ≥50 years of age from São Paulo, Brazil. Clinical data were collected through semistructured interviews with an informant and included in the Informant Questionnaire on Cognitive Decline in the Elderly, the Clinical Dementia Rating, and the Neuropsychiatric Inventory. Neuropathologic assessment relied on internationally accepted criteria. AGD was frequent (15.2%) and was the only neuropathological diagnosis in 8.9% of all cases (mean, 78.9 ± 9.4 years); it rarely occurred as an isolated neuropathological finding. AGD was associated with older age, lower socioeconomic status (SES), and appetite disorders. This is the first study of demographic, clinical, and neuropathological aspects of AGD in different ethnicities and subjects from all socioeconomic strata. The results suggest that prospective studies of AGD patients include levels of hormones related to appetite control as possible antemortem markers. Moreover, understanding the mechanisms behind higher susceptibility to AGD of low SES subjects may disclose novel environmental risk factors for AGD and other neurodegenerative diseases.

Transactive response DNA binding protein 43 (TDP-43) proteinopathy is the major hallmark of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. It is also present in a subset of Alzheimer's disease cases. Recently, few reports showed TDP-43 changes in cognitively normal elderly. In Caucasians, TDP-43 proteinopathy independently correlate with cognitive decline. However, it is challenging to establish direct links between cognitive and/or neuropsychiatric symptoms and protein inclusions in neurodegenerative diseases because individual cognitive reserves modify the threshold for clinical disease expression. Cognitive reserve is influenced by demographic, environmental and genetic factors. We investigated the relationships between demographic, clinical and neuropathological variables and TDP-43 proteinopathy in a large multiethnic sample of cognitively normal elderly. TDP-43 proteinopathy was identified in 10.5%, independently associated with older age (P = 0.03) and Asian ethnicity (P = 0.002). Asians showed a higher prevalence of TDP-43 proteinopathy than Caucasians, even after adjustment for sex, age, Braak stage and schooling (odds ratio = 3.50, confidence interval 1.41-8.69, P = 0.007). These findings suggested that Asian older adults may be protected from the clinical manifestation of brain TDP-43 proteinopathy. Future studies are needed to identify possible race-related protective factors against clinical expression of TDP-43 proteinopathies.

ObjectiveCognitive impairment is associated with reductions in brain weight and volume. The factors related to morphometric brain changes in cognitively normal aging remain unknown. We aimed to identify which clinical factors are associated with morphometric brain changes in cognitively normal aging.MethodsA cross-sectional study of 414 subjects, ≥50 years old submitted to clinical assessment and brain autopsy, after informed consent, was carried out at the São Paulo Autopsy Service, Brazil. Data on cognitive and functional evaluations were collected through structured interview applied to the next-of-kin. Brain weight (g) and volume (mL) measurements were obtained and adjusted for head circumference (cm). Associations between brain weight/volume and related factors were obtained through univariate and multivariate analysis.ResultsParticipants were predominantly male (60.4%), Caucasian (69%), with mean age of 67.1 ± 10.9 years. Mean brain weight was 1219.2 ± 140.9 g, and mean brain volume was 1217.1 ± 152.3 mL. Head circumference was independently associated with low brain weight (p

Despite a massive research effort to elucidate Alzheimer's disease (AD) in recent decades, effective treatment remains elusive. This failure may relate to an oversimplification of the pathogenic processes underlying AD and also lack of understanding of AD progression during its long latent stages. Although evidence shows that the two specific neuropathological hallmarks in AD (neuronal loss and protein accumulation), which are opposite in nature, do not progress in parallel, the great majority of studies have focused on only one of these aspects. Furthermore, research focusing on single structures is likely to render an incomplete picture of AD pathogenesis because as AD involves complete brain networks, potential compensatory mechanisms within the network may ameliorate impairment of the system to a certain extent. Here, we describe an approach for enabling integrative analysis of the dual-nature lesions, simultaneously, in all components of one of the brain networks most vulnerable to AD. This approach is based on significant development of methods previously described mainly by our group that were optimized and complemented for this study. It combines unbiased stereology with immunohistochemistry and immunofluorescence, making use of advanced graphics computing for three-dimensional (3D) volume reconstructions. Although this study was performed in human brainstem and focused in AD, it may be applied to the study of any neurological disease characterized by dual-nature lesions, in humans and animal models. This approach does not require a high level of investment in new equipment and a significant number of specimens can be processed and analyzed within a funding cycle.

Alzheimer's disease is the commonest cause of dementia in the elderly, but its pathological determinants are still debated. Amyloid-β plaques and neurofibrillary tangles have been implicated either directly as disruptors of neural function, or indirectly by precipitating neuronal death and thus causing a reduction in neuronal number. Alternatively, the initial cognitive decline has been attributed to subtle intracellular events caused by amyloid-β oligomers, resulting in dementia after massive synaptic dysfunction followed by neuronal degeneration and death. To investigate whether Alzheimer's disease is associated with changes in the absolute cell numbers of ageing brains, we used the isotropic fractionator, a novel technique designed to determine the absolute cellular composition of brain regions. We investigated whether plaques and tangles are associated with neuronal loss, or whether it is dementia that relates to changes of absolute cell composition, by comparing cell numbers in brains of patients severely demented with those of asymptomatic individuals-both groups histopathologically diagnosed as Alzheimer's-and normal subjects with no pathological signs of the disease. We found a great reduction of neuronal numbers in the hippocampus and cerebral cortex of demented patients with Alzheimer's disease, but not in asymptomatic subjects with Alzheimer's disease. We concluded that neuronal loss is associated with dementia and not the presence of plaques and tangles, which may explain why subjects with histopathological features of Alzheimer's disease can be asymptomatic; and exclude amyloid-β deposits as causes for the reduction of neuronal numbers in the brain. We found an increase of non-neuronal cell numbers in the cerebral cortex and subcortical white matter of demented patients with Alzheimer's disease when compared with asymptomatic subjects with Alzheimer's disease and control subjects, suggesting a reactive glial cell response in the former that may be related to the symptoms they present.

ObjectiveWe conducted a clinicopathologic study in a large population with very low levels of education to determine whether very few years of education could contribute to cognitive reserve and modify the relation of neuropathologic indices to dementia.MethodsIn this cross-sectional study, we included 675 individuals 50 years of age or older from the Brazilian Aging Brain Study Group. Cognitive abilities were evaluated through a structured interview with an informant at the time of autopsy, including the Clinical Dementia Rating (CDR) scale. Neuropathologic examinations were performed using immunohistochemistry and following internationally accepted criteria. Multivariate linear regression models were conducted to determine whether the association between cognitive abilities (measured by CDR sum of boxes) and years of education was independent of sociodemographic variables and neuropathologic indices, including neuritic plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and Lewy bodies. In addition, interaction models were used to examine whether education modified the relation between neuropathologic indices and cognition.ResultsMean education was 3.9 ± 3.5 years. Formal education was associated with a lower CDR sum of boxes (β = -0.197; 95% confidence interval -0.343, -0.052; p = 0.008), after adjustment for sociodemographic variables and neuropathologic indices. Furthermore, education modified the relationship of lacunar infarcts with cognitive abilities (p = 0.04).ConclusionsEven a few years of formal education contributes to cognitive reserve.

The present study aimed to establish the morphometric brain changes during aging in a necropsy series from Brazil and determine whether sexual dimorphisms interfere in these changes.MethodsA cross-sectional study was conducted at the São Paulo Autopsy Service in Brazil where, after informed consent, data was gathered from next of kin interview with reference to clinical status prior to death. Brain weight, volume and density measurements were taken and then adjusted for head circumference. Descriptive statistics and tests of hypothesis and correlations were applied, considering a p-value of 0.05.Results414 subjects, mostly men (60.4%), with a mean age of 67.1 years, were included. The mean brain weight of the sample was 1219.2g±140.9and mean volume was 1217mL±152.3. The mean brain density of the sample was 1.0g/mL±0.09. Values differed between males and females in terms of weight and volume. Brain weight decreased during aging by about 45g per decade (r= -0.300; p

The present study aimed to establish the morphometric brain changes during aging in a necropsy series from Brazil and determine whether sexual dimorphisms interfere in these changes. Methods:A cross-sectional study was conducted at the São Paulo Autopsy Service in Brazil where, after informed consent, data was gathered from next of kin interview with reference to clinical status prior to death. Brain weight, volume and density measurements were taken and then adjusted for head circumference. Descriptive statistics and tests of hypothesis and correlations were applied, considering a p-value of 0.05. Results:414 subjects, mostly men (60.4%), with a mean age of 67.1 years, were included. The mean brain weight of the sample was 1219.2g±140.9and mean volume was 1217mL±152.3. The mean brain density of the sample was 1.0g/mL±0.09. Values differed between males and females in terms of weight and volume. Brain weight decreased during aging by about 45g per decade (r= -0.300; p

The diagnosis of normal cognition or dementia in the Brazilian Brain Bank of the Aging Brain Study Group (BBBABSG) has relied on postmortem interview with an informant. Objectives:To ascertain the sensitivity and specificity of postmortem diagnosis based on informant interview compared against the diagnosis established at a memory clinic. Methods:A prospective study was conducted at the BBBABSG and at the Reference Center for Cognitive Disorders (RCCD), a specialized memory clinic of the Hospital das Clínicas, University of São Paulo Medical School. Control subjects and cognitively impaired subjects were referred from the Hospital das Clínicas to the RCCD where subjects and their informants were assessed. The same informant was then interviewed at the BBBABSG. Specialists' panel consensus, in each group, determined the final diagnosis of the case, blind to other center's diagnosis. Data was compared for frequency of diagnostic equivalence. For this study, the diagnosis established at the RCCD was accepted as the gold standard. Sensitivity and specificity were computed. Results:Ninety individuals were included, 45 with dementia and 45 without dementia (26 cognitively normal and 19 cognitively impaired but non-demented). The informant interview at the BBBABSG had a sensitivity of 86.6% and specificity of 84.4% for the diagnosis of dementia, and a sensitivity of 65.3% and specificity of 93.7% for the diagnosis of normal cognition. Conclusions:The informant interview used at the BBBABSG has a high specificity and sensitivity for the diagnosis of dementia as well as a high specificity for the diagnosis of normal cognition.

Background: Coronary atherosclerosis assessed in vivo was associated with cognitive impairment; however, conflicting findings have been reported in autopsy samples. Objective: Our aims were to assess the association between atherosclerotic stenosis in the coronary arteries and cognitive impairment and to investigate the possibility of selection bias in an autopsy study. Methods: Coronary arteries were collected, and the largest luminal stenosis was measured. Sociodemographic, clinical, and cognitive information were reported by a reliable next-of-kin. The association was tested using logistic and linear regressions adjusted for sociodemographic and clinical variables. We restricted the sample to individuals that were born in 1935 or earlier and stratified the analysis by cause of death to investigate the role of selection bias. Results: In 253 participants (mean age = 78.0±8.5 years old, 48% male), stenosis was not associated with cognitive impairment (OR = 0.85, 95% CI = 0.69; 1.06, p = 0.15). In individuals who were born before 1936 in the absence of cardiovascular disease as the cause of death, greater stenosis was associated with cognitive impairment (OR = 4.02, 95% CI = 1.39; 11.6, p = 0.01). On the other hand, this association was not present among those born in 1935 or earlier who died of cardiovascular diseases (OR = 0.83, 95% CI = 0.60; 1.16, p = 0.28). Conclusion: We found that higher coronary stenosis was associated with cognitive impairment only in individuals born in 1935 or earlier and who had not died from cardiovascular diseases. Selection bias may be an important issue when investigating risk factors for chronic degenerative diseases in older individuals using autopsy samples. [ABSTRACT FROM AUTHOR]

Sarcopenia is a progressive skeletal muscle disorder associated with aging, resulting in loss of muscle mass and function. It has been linked to inflammation, oxidative stress, insulin resistance, hormonal changes (i.e. alterations in the levels or activity of hormones which can occur due to a variety of factors, including aging, stress, disease, medication, and environmental factors), and impaired muscle satellite cell activation. The gut microbiome is also essential for muscle health, and supplements such as probiotics, prebiotics, protein, creatine, and beta-alanine can support muscle growth and function while also promoting gut health. Chronic low-grade inflammation is a leading cause of sarcopenia, which can activate signaling pathways that lead to muscle wasting and reduce muscle protein synthesis. Insulin resistance, hormonal changes, and impaired muscle satellite cell activation contribute to sarcopenia, and high levels of fat mass also play a role in the pathogenesis of sarcopenia. Resistance exercise and dietary supplementation have been shown to be effective treatments for sarcopenia. In addition, a combination of resistance exercise and supplementation has been shown to have a more significant beneficial effect on anthropometric and muscle function parameters, leading to a decrease in sarcopenic state. Thus, understanding the relationship between the gut microbiome and muscle metabolism is crucial for developing new treatments for sarcopenia across age groups. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to correlate oral and general health in frail and non-frail older adults. Methods: This observational study included 52 older adults, of whom 35 were frail (Frail Group), and 17 were non-frail (Non-Frail Group), according to Fried's self-reported test addressing oral health variables, number of systemic diseases, and medications in use. The geriatric oral health assessment index was used to assess the oral hygiene of the groups. Results: The number of preserved teeth in dentulous older adults was significantly higher in the Non-Frail Group (p=0.048). No significant differences were observed between the two groups in the use of dental prostheses or in the detection of soft tissue lesions. Overall, 74.3% of the Frail Group had a "bad" geriatric oral health index score, which significantly differed from that of the Non-Frail Group (p=0.045). The numbers of systemic diseases and medicines used were higher in the Frail Group than in the Non-Frail Group (p<0.001), demonstrating the pathophysiological characteristics of multimorbidity and polypharmacy in frailty syndrome. Conclusion: The results showed a clear correlation between oral and general health conditions and frailty syndrome. [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and dementia in deceased individuals who underwent a full-body autopsy examination. Methods: Weight and height were measured before the autopsy exam. Cognitive function before death was investigated using the Clinical Dementia Rating (CDR) scale. The cross-sectional association between BMI and dementia was investigated using linear regression models adjusted for sociodemographic and clinical variables. Results: We included 1,090 individuals (mean age 69.5 ± 13.5 years old, 46% women). Most participants (56%) had a normal BMI (18.5–24.9 kg/m2), and the prevalence of dementia was 16%. Twenty-four percent of the sample had cancer, including 76 cases diagnosed only by the autopsy examination. Moderate and severe dementia were associated with lower BMI compared with participants with normal cognition in fully adjusted models (moderate: β = −1.92, 95% CI = −3.77 to −0.06, p = 0.042; severe: β = −2.91, 95% CI = −3.97 to −1.86, p < 0.001). Conclusion: BMI was associated with moderate and severe dementia in late life, but we did not find associations of BMI with less advanced dementia stages. [ABSTRACT FROM AUTHOR]

Objective: We examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables.Methods: In this study, 1373 participants (787 male) aged 50 years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull.Results: Mean age at death was 68.6 ± 11.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p < 0.001), lower education (years; p < 0.001), hypertension (p = 0.001), diabetes (p = 0.006), and female gender (p < 0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (β = -0.86, 95% CI = -26.50 to 24.77, p = 0.95).Conclusions: In this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: The clinical symptoms of Alzheimer's disease (AD) are preceded by a long asymptomatic period associated with "silent" deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate (r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD. [ABSTRACT FROM AUTHOR]

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