The ACE Gene Is Associated with Late-Life Major Depression and Age at Dementia Onset in a Population-Based Cohort

Objective Depression and dementia in the elderly have been suggested to share similar risk factors and pathogenetic background, and recently the authors reported that the APOEɛ4 allele is a risk factor for both disorders in the general population. The aim of the present study was to examine the influence of the well-known polymorphisms rs1799752 in the angiotensin-converting enzyme (ACE) and rs5186 in the angiotensin receptor II type 1 (AGTR1) on late-life depression and dementia in a population-based Swedish cohort of older individuals followed over 12 years. Methods In 2000–2001, 900 individuals underwent neuropsychiatric and neuropsychological examinations. Follow-up evaluations were performed in 2005–2006 and 2009–2010, and register data on dementia to 2012 were included. Cross-sectional associations between genotypes/alleles and depression and dementia at baseline and between genotypes/alleles and depression on at least one occasion during the study period and dementia onset to 2012 were investigated. Results As previously found for rs1799752 in ACE, rs5186 in AGTR1 was associated with dementia at baseline (OR: 3.25 [CI: 1.42–7.06], z = 2.90, p = 0.004). These associations became substantially weaker, or disappeared, when dementia onset to 2012 was included. For rs1799752 this could be explained by a significant association with age at onset (mean: 79.5 [SD: 6.45] years for risk-genotype carriers and 81.7 [SD: 7.12] years for carriers of other genotypes, b = −2.43, t = −2.38, df = 192, p = 0.02). When individuals with major depression on at least one occasion were analyzed, a significant association (OR: 2.14 [95% CI: 1.13–4.20], z = 2.28, p = 0.02), remaining after exclusion of dementia, with rs1799752 in ACE was found. Conclusion In this population-based sample of older individuals, genetic variations in ACE seem to be important both for late-life major depression and dementia

A novel canine histiocytic sarcoma cell line:initial characterization and utilization for drug screening studies

In order to be responsible stewards of other people’s data, cloud providers must be accountable for their data handling practices. The potential long provider chains in cloud computing introduces additional accountability challenges, and this paper examines requirements which must be fulfilled to achieve an accountability-based approach.acceptedVersio

A novel canine histiocytic sarcoma cell line:initial characterization and utilization for drug screening studies

Abstract Background Histiocytic sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine histiocytic sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. Methods The histiocytic sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test. Results Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin. Conclusions In the present study we demonstrated that a novel canine histiocytic sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans

Midlife respiratory function related to white matter lesions and lacunar infarcts in late life: The prospective population study of women in Gothenburg, Sweden

BACKGROUND AND PURPOSE - Increased evidence suggests that poor respiratory function increases risk of ischemic damage to the brain. Longitudinal studies on respiratory function and cerebral small-vessel disease are lacking. We examined midlife and late-life respiratory function in relation to small-vessel disease on computed tomography (CT) in women followed for 26 years. METHODS - White matter lesions (WMLs) and lacunar infarcts were rated on brain CT scans in 2000 in 379 women 70 to 92 years of age from a longitudinal population study in G\uc3\ub6teborg, Sweden. Respiratory function was measured by peak expiratory flow (PEF) in 1974 and 2000 and by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in 1980 and 2000. RESULTS - Lower FVC and FEV1 in 1980 and 2000 were associated with presence and severity of WMLs and lacunar infarcts in 2000. Per 1-SD decrease of FVC in 1980, odds ratios (95% CIs) were 1.49 (1.11 to 2.02) for presence of WMLs and 1.95 (1.34 to 2.84) for lacunar infarcts after adjustment for potential confounders. Per 1-SD decrease of FEV1 in 1980, adjusted odds ratios were 1.46 (1.06 to 2.00) for presence of WMLs and 1.42 (1.02 to 1.97) for lacunar infarcts. PEF in 1974 and 2000 was not associated with WMLs or lacunar infarcts. CONCLUSIONS - WMLs and lacunar infarcts in elderly women were related to lower midlife respiratory function. Although our data may not establish causation between lower respiratory function and small-vessel disease, they imply the importance of good respiratory function in midlife

Prevalence of CT-detected cerebral abnormalities in an elderly Swedish population sample

Objective - To measure the prevalence of computed tomography (CT)-detected cerebral lesions in a population-based sample of elderly persons living in G\uf6teborg, Sweden. Methods - Cerebral CT-scans were performed in the case of 466 women (mean age 74.3 \ub1 5.1 years) and 191 70-year-old men. A single rater assessed white matter lesions (WML) using four different scales, lacunar lesions, large infarcts, cortical atrophy, and basal ganglia calcifications. Results - White matter lesions frequency assessed by different scales ranged between 54.5% and 68.5%. Lacunar lesions were detected in 46.7% (30.1% had lacunes >5 mm) and cerebral infarcts in 3.0% of participants. Overall, 72.8% of participants evidenced cerebral vascular abnormalities. Severe cortical atrophy was more common in temporal (6.4%) and frontal (6.7%) lobes, than in parietal (1.7%) and occipital (1.1%) lobes. Basal ganglia calcifications were found in 38.7% of participants. WML, lacunar lesions, large infarcts, and degree of cortical atrophy correlated positively with age. More lacunes, basal ganglia calcifications, and occipital lobe atrophy were associated with male gender. Conclusions - Vascular and other brain lesions are very common on CT-scan in an elderly population, but large vascular lesions are rare. This study provides the first reference for the prevalence of CT-detected abnormalities in an elderly Swedish population

Blood pressure components and changes in relation to white matter lesions : a 32-year prospective population study

This study aimed to examine the long-term effect of high blood pressure (systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure) on white matter lesions and to study changes in different blood pressure components in relation to white matter lesions. A representative population of women was examined in 1968 and re-examined in 1974, 1980, 1992, and 2000. The presence and severity of white matter lesions on computed tomography were rated by a visual rating scale in 1992 and 2000 in 539 women. Systolic and diastolic blood pressures were measured at all of the examinations. We found that presence and severity of white matter lesions in 1992/2000 were associated with higher diastolic blood pressure and mean arterial pressure at each examination but not with systolic blood pressure and pulse pressure. Odds ratios (95% CIs) for the presence of white matter lesions per 10-mm Hg increase in diastolic pressure were 1.4 (1.0 to 1.9) in 1968, 1.3 (1.0 to 1.8) in 1974, 1.4 (1.1 to 1.9) in 1980, and 1.3 (1.0 to 1.6) in 1992 after adjustment for confounders. The presence of white matter lesions was also associated with a 24-year increase in diastolic pressure (>10 mm Hg), systolic pressure (>40 mm Hg), pulse pressure (>24 mm Hg), and mean arterial pressure (>6 mm Hg; odds ratios [95% CIs]: 2.6 [1.3 to 5.1] for diastolic pressure; 2.0 [1.2 to 3.4] for systolic pressure; 1.8 [1.1 to 2.7] for pulse pressure; and 2.2 [1.4 to 3.4] for mean arterial pressure). Our findings suggest that lowering high diastolic blood pressure and preventing large increases in systolic and diastolic blood pressures may have a protective effect on white matter lesions

The pattern of cognitive symptoms predicts time to dementia onset.

Item does not contain fulltextBACKGROUND: Few studies have examined whether cognitive symptom patterns differ by age and length of time before dementia onset. Our objective was to investigate whether different patterns of cognitive symptoms at ages 70, 75, and 79 years predict short-term (5 years) dementia onset. METHODS: A representative sample of 382 nondemented 70-year-olds from Gothenburg, Sweden was examined periodically up to age 90 years. Information on dementia in those lost to follow-up was obtained from medical records. Cognitive assessments at ages 70, 75, and 79 years included psychiatric and psychometric examinations. Four patterns of cognitive performance were examined in relation to dementia onset: (1) unimpaired cognition, (2) isolated low memory, (3) low non-memory, and (4) global low cognitive performance. RESULTS: Short-term onset was predicted by global low performance at ages 70, 75, and 79 years and by low non-memory performance at ages 70 and 75. Isolated low memory was not a short-term predictor at any examination, but it predicted long-term onset at ages 70 and 75 years. CONCLUSIONS: A global pattern of low cognitive performance predicts short-term but not long-term onset of dementia, whereas isolated low memory performance predicts dementia only in the long-term. Our findings also suggest that preclinical symptoms of dementia might differ by age