Large Autopsy Study Research Articles

Prevalence and clinicopathological features of primary age-related tauopathy (PART): A large forensic autopsy study.

Primary age-related tauopathy (PART), often regarded as a minimally symptomatic pathology of old age, lacks comprehensive cohorts across various age groups. We examined PART prevalence and clinicopathologic features in 1589 forensic autopsy cases (≥40 years old, mean age±SD 70.2±14.2 years). PART cases meeting criteria for argyrophilic grain diseases (AGD) were AGD+PART (n=181). The remaining PART cases (n=719, 45.2%) were classified as comorbid conditions (PART-C, n=90) or no comorbid conditions (pure PART, n=629). Compared to controls (n=208), Alzheimer's disease (n=133), and AGD+PART, PART prevalence peaked in the individuals in their 60s (65.5%) and declined in the 80s (21.5%). No significant clinical background differences were found (excluding controls). However, PART-C in patients inclusive of age 80 had a higher suicide rate than pure PART (p<0.05), and AGD+PART showed more dementia (p<0.01) and suicide (p<0.05) than pure PART. Our results advocate a reevaluation of the PART concept and its diagnostic criteria. We investigated 1589 forensic autopsy cases to investigate the features of primary age-related tauopathy (PART). PART peaked in people in their 60s in our study. Many PART cases over 80s had comorbid pathologies in addition to neurofibrillary tangles pathology. Argyrophilic grain disease and Lewy pathology significantly affected dementia and suicide rates in PART. Our results suggest that the diagnostic criteria of PART need to be reconsidered.

ASSOCIATION BETWEEN ALZHEIMER DISEASE AND CANCER: A POSTMORTEM CROSS‐SECTIONAL STUDY IN BRAZIL

AbstractBackgroundA biological mechanism in cancer promotion may have a protective role against AD1. Although disparities between the clinical and the anatomopathological postmortem diagnoses related to the etiology of dementia and cancer were described2, most previous studies were based only on the clinical diagnoses for both diseases. Therefore, we aimed to investigate the association between AD and cancer in a large autopsy study from a racially diverse sample.MethodThis cross‐sectional study analyzed data with postmortem brain tissue from participants over 55 years of age from the Biobank for Aging Studies. Data from the full‐body autopsy reports and a Functional Clinical Questionnaire (FCQ) applied to an informant were used to determine the presence of cancer. The association between AD and cancer was investigated using logistic and linear models adjusted for sociodemographic and clinical variables and APOE allele 4.Result689 subjects were included (mean age 74.2 ± 10.8 years old, 47.5% women, 68% White) (Table 1). 18% of the sample had cancer. The frequencies of cancer types and neuropathological post‐mortem diagnoses are shown in Figure 1. Cancer was not associated with AD (OR = 0.56, 95% CI = 0.21;1.39), or CERAD neuritic plaque score [ b = 0.057, 95% CI = ‐0.31; 0.41], but was associated with lower Braak neurofibrillary tangle staging (b = ‐0.49, 95% CI = ‐0.98; ‐0.03] (Table 2).ConclusionIn a large autopsy study, we found an association between cancer and Braak neurofibrillary tangle staging, which is in accordance with previous research suggesting a protective role of cancer in AD risk3.1. Ospina‐Romero M, Glymour MM, Hayes‐Larson E, Mayeda ER, Graff RE, Brenowitz WD, Ackley SF, Witte JS, Kobayashi LC. Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Metaanalysis. JAMA Netw Open. 2020 Nov 2;3(11):e2025515.2. Landefeld CS, Chren MM, Myers A, et al. Diagnostic yield of the autopsy in a university hospital and a community hospital. The New England Journal of Medicine. 1988 May;318(19):1249‐1254.3. Nakamura M, Kaneko S, Dickson DW, Kusaka H. Aberrant Accumulation of BRCA1 in Alzheimer Disease and Other Tauopathies. J Neuropathol Exp Neurol. 2020 Jan 1;79(1):22‐33.

High-throughput digital quantification of Alzheimer disease pathology and associated infrastructure in large autopsy studies.

High-throughput digital pathology offers considerable advantages over traditional semiquantitative and manual methods of counting pathology. We used brain tissue from 5 clinical-pathologic cohort studies of aging; the Religious Orders Study, the Rush Memory and Aging Project, the Minority Aging Research Study, the African American Clinical Core, and the Latino Core to (1) develop a workflow management system for digital pathology processes, (2) optimize digital algorithms to quantify Alzheimer disease (AD) pathology, and (3) harmonize data statistically. Data from digital algorithms for the quantification of β-amyloid (Aβ, n = 413) whole slide images and tau-tangles (n = 639) were highly correlated with manual pathology data (r = 0.83 to 0.94). Measures were robust and reproducible across different magnifications and repeated scans. Digital measures for Aβ and tau-tangles across multiple brain regions reproduced established patterns of correlations, even when samples were stratified by clinical diagnosis. Finally, we harmonized newly generated digital measures with historical measures across multiple large autopsy-based studies. We describe a multidisciplinary approach to develop a digital pathology pipeline that reproducibly identifies AD neuropathologies, Aβ load, and tau-tangles. Digital pathology is a powerful tool that can overcome critical challenges associated with traditional microscopy methods.

The Association Between Relative Deprivation, Depression, and Youth Suicide: Evidence From a Psychological Autopsy Study.

Suicide is a serious public health concern in China. In the present study, we investigated the specific mechanisms underlying relative deprivation and suicide in rural China. A large psychological autopsy study was conducted in rural China, in which 392 suicides and 416 community-living controls were consecutively recruited. Multiple logistic regression analysis was used to assess the relationship between relative deprivation and suicide, with depression as a potential mediator. Young people who experienced relative deprivation were at a greater risk of suicide and depression. Depression plays a mediating role in the relationship between relative deprivation and suicide. Due to the limitations of the data, we cannot know whether there is mutual causation between relative deprivation and depression. The self-reported relative deprivation may also produce some influence on the results. The current findings demonstrate the importance of relative deprivation as one of the four sources of psychological strain to explain how relative status is associated with suicide. The findings also can be translated into the clinical and preventive practice for suicide.

SARS-CoV-2, myocardial injury and inflammation: insights from a large clinical and autopsy study

ObjectiveDespite growing evidence about myocardial injury in hospitalized COronaVIrus Disease 2019 (COVID-19) patients, the mechanism behind this injury is only poorly understood and little is known about its association with SARS-CoV-2-mediated myocarditis. Furthermore, definite evidence of the presence and role of SARS-CoV-2 in cardiomyocytes in the clinical scenario is still lacking.MethodsWe histologically characterized myocardial tissue of 40 patients deceased with severe SARS-CoV-2 infection during the first wave of the pandemic. Clinical data were also recorded and analyzed. In case of findings supportive of myocardial inflammation, histological analysis was complemented by RT-PCR and immunohistochemistry for SARS-CoV-2 viral antigens and in situ RNA hybridization for the detection of viral genomes.ResultsBoth chronic and acute myocardial damage was invariably present, correlating with the age and comorbidities of our population. Myocarditis of overt entity was found in one case (2.5%). SARS-CoV-2 genome was not found in the cardiomyocytes of the patient with myocarditis, while it was focally and negligibly present in cardiomyocytes of patients with known viral persistence in the lungs and no signs of myocardial inflammation. The presence of myocardial injury was not associated with myocardial inflammatory infiltrates.ConclusionsIn this autopsy cohort of COVID-19 patients, myocarditis is rarely found and not associated with SARS-CoV-2 presence in cardiomyocytes. Chronic and acute forms of myocardial damage are constantly found and correlate with the severity of COVID-19 disease and pre-existing comorbidities.Graphic abstract

Kidney Cadmium Concentrations in an Urban Sri Lankan Population: an Autopsy Study.

Contamination and bioaccumulation of toxic heavy metals in our geo-environment is a growing public health concern. Human biomonitoring is an essential step in assessing the population risk of chronic exposure to environmental contaminants. Whole kidneys collected from a cohort of 92 deceased individuals undergoing forensic autopsies in Colombo, Sri Lanka, were analysed for cadmium (Cd) bioaccumulation using ICP-MS. Mean age of the population was 55.4 ± 15.4years. Mean and median renal Cd concentrations of the total population were 4.38 and 2.60μgg-1 w/w, respectively, which were below estimated toxic ranges. Males accumulated higher levels of Cd than females (p = 0.377). Cd concentrations were higher in the < 60 age group than the > 60 age group (p = 0.92), while the highest levels were reported in 51-60 age group. However, no significant correlation was found between renal Cd concentration and age (Ʈb = - 0.005, p = 0.94). Individuals who smoked, chewed betel or consumed alcohol were found to have elevated renal Cd concentrations in comparison to those who did not use these substances. This is the largest autopsy study on renal Cd bioaccumulation in Sri Lanka, and the findings do not indicate a high exposure risk to environmental Cd contamination at present.

COVID-19 and kidney involvement

Bei einer schweren COVID-19(„coronavirus disease 2019“)-Erkrankung ist neben der Lungenerkrankung das akute Nierenversagen eine der häufigsten und schwerwiegendsten Komplikationen. SARS-CoV‑2 („severe acute respiratory syndrome coronavirus 2“) konnte auch in der Niere nachgewiesen werden. Patienten mit chronischen Nierenerkrankungen und an der Dialyse wie auch nierentransplantierte Patienten scheinen eine besonders vulnerable Population darzustellen. Die zunehmende Anzahl SARS-CoV-2-infizierter Patienten hat das Interesse an der genauen Pathophysiologie und Morphologie der Nierenschädigung sowie am direkten Virusnachweis in der Niere geweckt, der im Gegensatz zur Lunge insgesamt schwieriger zu führen ist. Hierzu liegen mittlerweile Daten aus größeren Autopsie- und Nierenbiopsiestudien vor. Während der Nachweis von SARS-CoV-2-RNA im Gewebe zu gut reproduzierbaren Ergebnissen führt, wird insbesondere der Virusnachweis mittels Elektronenmikroskopie aufgrund zahlreicher Artefakte kritisch diskutiert. Die genauen und direkten Effekte von SARS-CoV‑2 auf die Niere sind noch nicht im Detail bekannt und derzeit im Fokus intensiver Forschung.

β-amyloid pathology is not associated with depression in a large community sample autopsy study

Background: Depression has been associated with dementia. This study aimed to verify if β-amyloid Alzheimer's disease-type burden was associated with lifetime major depressive disorder (MDD) and with current depressive symptoms in a large population-based autopsy study. Methods: We included 1013 deceased subjects submitted to autopsy (mean age=74.3±11.6 years, 49% men) in a community sample. β-amyloid burden was measured in all cases based on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for presence and density of neuritic plaques. Lifetime MDD was defined when at least one previous episode according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders – DSM (SCID). Depressive symptoms and cognitive impairment were determined using the depression item of the Neuropsychiatric Inventory (D-NPI>0) and the Clinical Dementia Rating scale (CDR>0.5) respectively. Results: Lifetime MDD, late life depression (LLD) and current depressive symptoms were associated with cognitive impairment (p<0.001). Additionally, neuritic plaques were associated with cognitive impairment (p<0.001). Moderate or frequent neurite plaque density was not associated with MDD, LLD or current depressive symptoms in multiple logistic models adjusted for age, gender, and cognitive impairment. Limitations: In this cross-sectional study, all neuropsychiatric and cognitive assessment were based on informant-report of deceased participants. Conclusions: Different clinical depictions of depression were associated with dementia in this large community sample of elderly individuals with multiethnic backgrounds. Notwithstanding, they were unrelated to β-amyloid pathology in the brain areas studied. The link between depression and dementia might be complex and determined by multiple factors.

Neuropathological lesions in the very old: results from a large Brazilian autopsy study.

To compare neuropathological correlates of cognitive impairment between very old and younger individuals from a Brazilian clinicopathological study. We 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. Except for infarcts and siderocalcinosis, all neuropathological lesions were more common in the 80 or over age group (n=412) compared to 50-79year 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]. Despite 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.

Pleural anthracosis as an indicator of lifetime exposure to urban air pollution: An autopsy-based study in Sao Paulo

Many studies have been conducted to evaluate the association between air pollution and adverse health effects using a wide variety of methods to assess exposure. However, the assessment of individual long-term exposure to ambient air pollution is a challenging task and has not been evaluated in a large autopsy study. Our goal was to investigate whether exposure to urban air pollution is associated to the degree of lung anthracosis, considering modifying factors such as personal habits, mobility patterns and occupational activities. We conducted a study in Sao Paulo, Brazil from February 2017 to June 2018, combining epidemiological, spatial analysis and autopsy-based approaches. Information about residential address, socio-demographic details, occupation, smoking status, time of residence in the city and time spent commuting was collected via questionnaires applied to the next-of-kin. Images of the pleura surface from upper and lower lobes were used to quantify anthracosis in the lungs. We used multiple regression models to assess the association between the amount of carbon deposits in human lungs, measured by the fraction of pleural anthracosis (FA), and potential explanatory variables. We analyzed 413 cases and our data showed that for each additional hour spent in daily commuting, the ratio FA/(1-FA) is multiplied by 1.05 (95% confidence interval: [1.02; 1.08]). The estimated coefficient for daily hours spent in traffic was not considerably affected by the inclusion of socio-demographic variables and smoking habits. We estimate a tobacco equivalent dose of 5 cigarettes per day in a city where annual PM2.5 concentration oscillates around 25 μg/m3. Pleural anthracosis is a potential index of lifetime exposure to traffic-derived air pollution.

Morphometric measurements of extracranial and intracranial atherosclerotic disease: A population-based autopsy study

Background and aimsIntracranial (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. MethodsWe 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. ResultsIn 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). ConclusionsIn this population-based autopsy study, IAD was common, even more common than EAD, but correlated with EAD.

Association between diabetes and causes of dementia: Evidence from a clinicopathological study.

ABSTRACT.Background:Diabetes mellitus is a risk factor for dementia, especially for vascular dementia (VaD), but there is no consensus on diabetes as a risk factor for Alzheimer's disease (AD) and other causes of dementia.Objective:To explore the association between diabetes and the neuropathological etiology of dementia in a large autopsy study.Methods:Data were collected from the participants of the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015. Diagnosis of diabetes was reported by the deceased's next-of-kin. Clinical dementia was established when CDR ≥ 1 and IQCODE > 3.41. Dementia etiology was determined by neuropathological examination using immunohistochemistry. The association of diabetes with odds of dementia was investigated using multivariate logistic regression.Results:We included 1,037 subjects and diabetes was present in 279 participants (27%). The prevalence of dementia diagnosis was similar in diabetics (29%) and non-diabetics (27%). We found no association between diabetes and dementia (OR = 1.22; 95%CI = 0.81-1.82; p = 0.34) on the multivariate analysis. AD was the main cause of dementia in both groups, while VaD was the second-most-frequent cause in diabetics. Other mixed dementia was the second-most-common cause of dementia and more frequent among non-diabetics (p = 0.03).Conclusion:Diabetes was not associated with dementia in this large clinicopathological study.

Diabetes is Not Associated with Alzheimer's Disease Neuropathology.

Previous evidence linking diabetes to Alzheimer's disease (AD) neuropathology is mixed and scant data are available from low- and middle-income countries. To investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults. In this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication. Astandardized 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. Among 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. No 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.

Metástases Cutâneas de Carcinoma de Células de Hürthle da Tiróide

Metástases cutâneas de neoplasias internas constituem um evento raro, ocorrendo em 0,9% a 4,4% em grandes estudos necrópsicos e atingindo 9% em grandes séries de doentes neoplásicos. Metástases cutâneas de carcinomas da tiróide são ainda mais raros e, entre eles, os de carcinomas foliculares foram mais raramente reportados, mais escassamente do que os de carcinomas papilares ou medulares. Um Eurocaucasiano de 57 A de idade recorreu à consulta por pápula angiomatoide na área parietal do couro cabeludo, com cerca de 4 meses de evolução. O doente tinha sido submetido, 2 anos antes, a tiroidectomia total, complementada com radioterapia e diversos esquemas quimioterapêuticos por um carcinoma metastático de células de Hürthle da tiróide. A biópsia excisional da pápula permitiu estabelecer, com recurso a estudos imuno-histoquímicos, o diagnóstico de metástase cutânea de carcinoma folicular da tiróide. Os gânglios linfáticos, pulmões e os ossos constituem as mais prevalentes localizações à distância das metástases do carcinoma folicular da tiróide. Embora estas neoplasias representem até 12% das neoplasias malignas da tiróide, metástases cutâneas destes tumores têm sido muito raramente reportadas. Estes tumores são habitualmente carcinomas bem diferenciados, com prognóstico favorável a longo termo e caracterizados histologicamente por estruturas foliculares com material colóide e variáveis anaplasia e distorção arquitectural. No caso apresentado merecem destaque a morfologia angiomatoide da lesão metastática, classicamente associada a metástases de tumores de células renais e a alguns casos já relatados de tumores de células de Hürthle, bem como o comportamento agressivo e a evolução fatal verificados. O caso é ilustrado iconograficamente e uma breve revisão da literatura é efectuada.

Psychological autopsy study comparing suicide decedents, suicide ideators, and propensity score matched controls: results from the study to assess risk and resilience in service members (Army STARRS).

The suicide rate has increased significantly among US Army soldiers over the past decade. Here we report the first results from a large psychological autopsy study using two control groups designed to reveal risk factors for suicide death among soldiers beyond known sociodemographic factors and the presence of suicide ideation. Informants were next-of-kin and Army supervisors for: 135 suicide cases, 137 control soldiers propensity-score-matched on known sociodemographic risk factors for suicide and Army history variables, and 118 control soldiers who reported suicide ideation in the past year. Results revealed that most (79.3%) soldiers who died by suicide have a prior mental disorder; mental disorders in the prior 30-days were especially strong risk factors for suicide death. Approximately half of suicide decedents tell someone that they are considering suicide. Virtually all of the risk factors identified in this study differed between suicide cases and propensity-score-matched controls, but did not significantly differ between suicide cases and suicide ideators. The most striking difference between suicides and ideators was the presence in the former of an internalizing disorder (especially depression) and multi-morbidity (i.e. 3+ disorders) in the past 30 days. Most soldiers who die by suicide have identifiable mental disorders shortly before their death and tell others about their suicidal thinking, suggesting that there are opportunities for prevention and intervention. However, few risk factors distinguish between suicide ideators and decedents, pointing to an important direction for future research.

Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study.

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. 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. 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). 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.

Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study.

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.

High Rate of Cardiac Abnormalities in a Postmortem Analysis of Patients Suffering From Liver Cirrhosis.

Cirrhotic cardiomyopathy is a recently defined cardiac disorder in patients with end-stage liver disease. The frequency and exact manifestations of cardiac changes in liver cirrhosis is unknown. We aim to describe cardiac changes in a large autopsy study of patients with liver cirrhosis. Postmortem data from 895 individuals with liver cirrhosis of different origin autopsied from 1995 to 2010 were analyzed. A total of 236 patients were excluded, mostly due to an advanced age above 70 years. The remaining 659 patients were assigned to 4 subgroups according to the etiology of cirrhosis: alcoholic cirrhosis (57.4%), nonalcoholic steatohepatitis (4.2%), viral hepatitis (9.3%), and cryptogenic cirrhosis (29.1%). Predefined clinical and cardiac parameters were assessed in these groups and compared by univariate and multivariate analyses to an age-matched and sex-matched control group including 40 deceased patients without evidence of chronic liver disease. A critical heart weight (24%, P=0.024), hypertrophy of the right ventricle (24%, P<0.001), and dilatation of the right ventricle (36%, P=0.040) were significantly more frequent in the cirrhosis group compared with noncirrhotic controls. Cirrhosis patients had a greater risk for high-grade coronary sclerosis (30%, P=0.019). The etiology of cirrhosis was independently associated with hypertrophy and dilatation of the right ventricle, with nonalcoholic steatohepatitis patients being at the highest risk. Our results demonstrate a high rate of right-ventricular abnormalities and coronary sclerosis in individuals suffering from liver cirrhosis regardless of the etiology of cirrhosis.

Using current data to define new approach in age related macular degeneration: need to accelerate translational research.

Age related macular degeneration (AMD) is one of the major retinal degenerative disease of ageing whose complex genetic basis remains undeciphered. The involvement of various other factors like mitochondrial genes, cytoskeletal proteins and the role of epigenetics has been described in this review. Several population based AMD genetic studies have been carried out worldwide. Despite the increased publication of reports, clinical translation still eludes this davastating disease. We suggest models to address roadblocks in clinical translation hoping that these would be beneficial to drive AMD research towards innovative biomarkers and therapeutics Therefore, addressing the need large autopsy studies and combining it with efficient use of bioinformatic tools, statistical modeling and probing SNP-biomarker association are key to time bound resolution of this disease.

Associations of Cerebrovascular and Alzheimer’s Disease Pathology with Brain Atrophy

Cortical atrophy and brain vascular disease are both associated with dementia, but there are only limited pathological data on the association of brain vascular disease with cortical atrophy. We studied pathological material from the Rush Memory and Aging Project (MAP, N = 445). Cortical and hippocampal atrophy, and atherosclerosis at the circle of Willis (large vessel disease, LVD) and arteriolosclerosis (small vessel disease, SVD) were rated by neuropathologists unaware of this study's hypothesis. Quantitative measures of Alzheimer's disease (AD) pathology, specifically neuronal neurofibrillary tangles (NFT) and amyloid-beta (Aβ) burden, were also obtained. Chronic micro and macroscopic infarcts were noted. In ordinal logistic regression models that included age at death, sex, apoE genotype, statin-use, Aβ and NFT, more severe LVD was significantly associated with more severe cortical and hippocampal atrophy. The odds ratio for the association of the most severe LVD (compared to the least) with cortical atrophy was 2.7 (CI: 1.5-4.7) p = 0.001; for hippocampal atrophy the odds ratio was 2.8 (CI: 1.5-5.2), p = 0.001. The association of SVD with atrophy did not follow a consistent pattern. Neither macroscopic infarcts nor microscopic infarcts were associated with cortical or hippocampal atrophy (p's > 0.15). Tangle density was associated with cortical (p = 0.014) and hippocampal atrophy (p < 0.001). In contrast, amyloid burden was associated with less cortical (p = 0.02) or hippocampal (p = 0.002) atrophy. In this large autopsy study LVD was associated with cortical and hippocampal atrophy. The relationship between SVD and atrophy requires further study.