BackgroundFew pathologic data are available on cerebral vessel disease, dementia, and cognition. This cross-sectional study examined associations of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer’s disease (AD) dementia and level of cognitive function, in a large group of older persons who came to autopsy.Methods1,143 older women or men (median age-at-death = 88.8 years; 42% with AD dementia) underwent annual clinical evaluations and agreed to brain autopsy at time-of-death, as part of one of two cohort studies of aging. Neuropsychological data proximate-to-death were used to create summary measures of global cognition and cognitive domains. Data across all years were used to determine presence of the clinical syndrome of AD dementia. Systematic neuropathologic evaluations documented severity of cerebral large (atherosclerosis) and small vessel disease (arteriolosclerosis). Using regression analyses adjusted for demographics, gross and micro-infarcts and AD pathology, we examined associations of vessel disease severity with odds of probable and possible AD dementia and level of cognition.FindingsModerate-to-severe atherosclerosis was present in 445 (39%) subjects, and arteriolosclerosis in 401 (35%). The odds of AD dementia was higher with moderate-to-severe atherosclerosis (OR=1.33; 95%CI:1.11–1.58) and arteriolosclerosis (OR=1.20; 95%CI:1.04–1.40). Atherosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.04; p=0.00096) and four cognitive domains (episodic memory, semantic memory, perceptual speed and visuospatial abilities; all p<0.019) but not working memory (p=0.21). Arteriolosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.03; p=0.0015) and four domains (all p<0.046), and a borderline/non-significant association was noted for visuospatial abilities (p=0.052). Findings were unchanged in analyses controlling for APOEε4 and vascular risk factors.InterpretationCerebral atherosclerosis and arteriolosclerosis each contribute to the odds of AD dementia by 20–30% per level increase in severity, and are associated with lower scores in most cognitive domains. Associations remain after taking into account AD and infarct pathologies, and vascular factors. Cerebral vessel pathology may be an under-recognized risk factor for AD dementia.FundingUnited States National Institutes of Health.

BackgroundRecent research has demonstrated that many swine and swine farmers in the Netherlands and Canada are colonized with MRSA. However, no studies to date have investigated carriage of MRSA among swine and swine farmers in the United States (U.S.).MethodsWe sampled the nares of 299 swine and 20 workers from two different production systems in Iowa and Illinois, comprising approximately 87,000 live animals. MRSA isolates were typed by pulsed field gel electrophoresis (PFGE) using SmaI and EagI restriction enzymes, and by multi locus sequence typing (MLST). PCR was used to determine SCCmec type and presence of the pvl gene.ResultsIn this pilot study, overall MRSA prevalence in swine was 49% (147/299) and 45% (9/20) in workers. The prevalence of MRSA carriage among production system A's swine varied by age, ranging from 36% (11/30) in adult swine to 100% (60/60) of animals aged 9 and 12 weeks. The prevalence among production system A's workers was 64% (9/14). MRSA was not isolated from production system B's swine or workers. Isolates examined were not typeable by PFGE when SmaI was used, but digestion with EagI revealed that the isolates were clonal and were not related to common human types in Iowa (USA100, USA300, and USA400). MLST documented that the isolates were ST398.ConclusionsThese results show that colonization of swine by MRSA was very common on one swine production system in the midwestern U.S., suggesting that agricultural animals could become an important reservoir for this bacterium. MRSA strain ST398 was the only strain documented on this farm. Further studies are examining carriage rates on additional farms.

Objective To investigate the association of hippocampal sclerosis (HS) with TAR-DNA binding protein of 43 kDa (TDP-43) and other common age-related pathologies, dementia, probable Alzheimer’s disease (AD), mild cognitive impairment (MCI) and cognitive domains in community-dwelling older subjects. Methods Diagnoses of dementia, probable AD and MCI in 636 autopsied subjects from the Religious Order Study and the Rush Memory and Aging Project were based on clinical evaluation and cognitive performance tests. HS was defined as severe neuronal loss and gliosis in the hippocampal CA1and/or subiculum. The severity and distribution of TDP-43 was assessed and other age-related pathologies were also documented. Results HS was more common in those aged > 90 years (18.0%) compared to younger subjects (9.2%). HS cases commonly coexisted with TDP-43 pathology (86%), which was more severe (p < 0.001) in HS cases. Although, HS also commonly coexisted with AD and Lewy body (LB) pathology; only TDP-43 pathology increased the odds of HS (OR=2.63; 95% CI 2.07-3.34). In logistic regression models accounting for age, TDP-43 and other common age-related pathologies; HS cases had higher odds of dementia (OR=3.71; 95% CI=1.93-7.16), MCI and probable AD (OR=3.75; 95% CI=2.01-7.02). In linear regression models, including an interaction term for HS and TDP-43 pathology; HS with coexisting TDP-43 was associated with lower function in multiple cognitive domains while HS without TDP-43 did not have statistically significant associations. TDP-43 without HS was separately related to lower episodic memory. Interpretation The combined role of hippocampal sclerosis and TDP-43 pathology are significant factors underlying global cognitive impairment and probable AD in older subjects.

Background.Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus.Methods. In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during [2004][2005][2006]. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method.Results. Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%).Conclusions. For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age !7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.

Occupational exposure to pigs greatly increases workers' risk of swine influenza virus infection. Swine workers should be included in pandemic surveillance and in antiviral and immunization strategies.