Despite a non-specific nature of self-rated health (SRH), it seems to be a strong predictor of mortality. The aim of this study is to assess the association of SRH and objective health status (OH) ...with all-cause mortality in 70-year-old community-dwelling older people in Finland.
A prospective study with 5-, 10- and 27-year follow-ups. SRH (n = 1008) was assessed with a single question and OH (n = 962) by the Rockwood's Frailty Index (FI). To assess the association of SRH and OH with mortality, Cox regression model was used.
Of the 1008 participants, 138 (13.7%), 319 (31.6%), and 932 deceased (86.3%) during the 5-, 10- and 27-year follow-ups, respectively. In unadjusted models, subjects with poor SRH had almost eightfold risk for mortality compared to those with good SRH during the 5-year follow-up; among those with poor OH, the risk was fourfold compared to those with good OH. In the 10-year-follow up, both poor SRH and poor OH predicted about fourfold risk for mortality compared to those with good health. During the 27-year follow-up, OH was a stronger predictor of mortality than SRH. Poor SRH, compared to good SRH, showed 95% sensitivity and 34% specificity for 5-year mortality; corresponding figures for OH were 54 and 80%, respectively.
Single-item SRH seems to be able to capture almost the same as OH in predicting a short-term (less than 10 years) mortality risk among older adults in clinical settings. The use of SHR may also enhance the focus on patient-centered care.
The aim of this study was to examine whether insulin resistance, assessed by HOMA of insulin resistance (HOMA-IR), is an independent predictor of cognitive decline.
The roles of HOMA-IR, fasting ...insulin and glucose, HbA
, and hs-CRP as predictors of cognitive performance and its change were evaluated in the Finnish nationwide, population-based Health 2000 Health Examination Survey and its 11-year follow-up, the Health 2011 study (
= 3,695, mean age at baseline 49.3 years, 55.5% women). Categorical verbal fluency, word-list learning, and word-list delayed recall were used as measures of cognitive function. Multivariate linear regression analysis was performed and adjusted for previously reported risk factors for cognitive decline.
Higher baseline HOMA-IR and fasting insulin levels were independent predictors of poorer verbal fluency performance (
= 0.0002 for both) and of a greater decline in verbal fluency during the follow-up time (
= 0.004 for both). Baseline HOMA-IR and insulin did not predict word-list learning or word-list delayed recall scores. There were no interactions between HOMA-IR and apolipoprotein E ε4 (
) genotype, hs-CRP, or type 2 diabetes on the cognitive tests. Fasting glucose and hs-CRP levels at baseline were not associated with cognitive functioning.
Our results show that higher serum fasting insulin and insulin resistance predict poorer verbal fluency and a steeper decline in verbal fluency during 11 years in a representative sample of an adult population. Prevention and treatment of insulin resistance might help reduce cognitive decline later in life.
We conducted a comparative analysis of hypertension prevalence, progression, and treatment in two Finnish population-based cohorts comprising older adults born 20 years apart. The study covered data ...from pre- and post-HYVET Study eras and spanned the onset of the COVID-19 pandemic.BACKGROUNDWe conducted a comparative analysis of hypertension prevalence, progression, and treatment in two Finnish population-based cohorts comprising older adults born 20 years apart. The study covered data from pre- and post-HYVET Study eras and spanned the onset of the COVID-19 pandemic.All 70-year-old home-dwelling citizens of Turku, in Southwest Finland, were invited to participate in the survey in 1990 (1920-born TUVA cohort) and in 2010 (1940-born UTUVA cohort) with a 25-year follow-up plan. The analyses included those with available data for systolic and diastolic blood pressure (BP), yielding 1015 TUVA and 888 UTUVA participants at baseline. Biomarkers associated with BP were analysed with t- and chi-square tests.METHODSAll 70-year-old home-dwelling citizens of Turku, in Southwest Finland, were invited to participate in the survey in 1990 (1920-born TUVA cohort) and in 2010 (1940-born UTUVA cohort) with a 25-year follow-up plan. The analyses included those with available data for systolic and diastolic blood pressure (BP), yielding 1015 TUVA and 888 UTUVA participants at baseline. Biomarkers associated with BP were analysed with t- and chi-square tests.At baseline, 83.4% of TUVA and 74.3% of UTUVA participants had uncontrolled BP, with respective antihypertensive medication usage at 36.0% and 55.9% (p < .001 for both between-cohort differences). Systolic BP exhibited an inverted U-shaped trajectory, with TUVA initially 7.8 mmHg higher at 155.4 mmHg than UTUVA (p < .001). However, by the ages 80-82, the difference in systolic BP trajectories between the cohorts was attenuated to 4.0 mmHg (p = .03). Diastolic BP differences were less clinically significant. UTUVA demonstrated higher use of all five conventional antihypertensive categories than TUVA (p ≤ .02 for all categories).RESULTSAt baseline, 83.4% of TUVA and 74.3% of UTUVA participants had uncontrolled BP, with respective antihypertensive medication usage at 36.0% and 55.9% (p < .001 for both between-cohort differences). Systolic BP exhibited an inverted U-shaped trajectory, with TUVA initially 7.8 mmHg higher at 155.4 mmHg than UTUVA (p < .001). However, by the ages 80-82, the difference in systolic BP trajectories between the cohorts was attenuated to 4.0 mmHg (p = .03). Diastolic BP differences were less clinically significant. UTUVA demonstrated higher use of all five conventional antihypertensive categories than TUVA (p ≤ .02 for all categories).In the early years of older adulthood, the 1940-born cohort showed a positive trend in hypertension management, yet maintained a 74.3% baseline rate of uncontrolled BP. Furthermore, by the ages 81-82, the benefits observed over the 1920-born cohort had lessened, influenced by the COVID-19 pandemic or other lasting factors. Heightened efforts to improve hypertension treatment in older adults remain crucial in the post-HYVET era.CONCLUSIONSIn the early years of older adulthood, the 1940-born cohort showed a positive trend in hypertension management, yet maintained a 74.3% baseline rate of uncontrolled BP. Furthermore, by the ages 81-82, the benefits observed over the 1920-born cohort had lessened, influenced by the COVID-19 pandemic or other lasting factors. Heightened efforts to improve hypertension treatment in older adults remain crucial in the post-HYVET era.
Chronic low-grade inflammation, commonly associated with cardiovascular diseases and risk factors, has been associated inconclusively with cognitive decline and dementia. The aim of our study was to ...evaluate whether low-grade inflammation, measured in midlife, is associated with a decline in cognitive performance after a 10-year follow-up. We hypothesized that low-grade inflammation, estimated by interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high-sensitivity CRP (hs-CRP), is a predictor of cognitive decline in the general population.
This prospective cohort study is based on a Finnish nationwide, population-based Health 2000 Examination Survey, its supplemental examinations in 2000-2001, and the follow-up Health 2011 Survey. Cognitive performance at baseline and at follow-up was assessed with categorical verbal fluency (VF), word-list learning (WLL), and word-list delayed recall (WLDR). Baseline low-grade inflammation was measured with IL-6, TNF-α, and hs-CRP in 2001. Associations between low-grade inflammation and cognitive performance were analyzed with multivariable linear models adjusted for age, sex, education,
genotype, type 2 diabetes, hypertension, hypercholesterolemia, body mass index, depressive symptoms, smoking, and baseline cognition.
Nine hundred fifteen participants aged 45-74 years (median age 54 years, 55% women) were included in the analysis. Both higher IL-6 and TNF-α at baseline predicted poorer performance in VF and WLL at 10-year follow-up (VF: IL-6 β: -1.14,
= 0.003, TNF-α β: -1.78,
= 0.008; WLL: IL-6 β: -0.61,
= 0.007, TNF-α β: -0.86,
= 0.03). Elevated IL-6 also predicted a greater decline in VF and WLL after a 10-year follow-up (VF: β: -0.81,
= 0.01; WLL: β: -0.53,
= 0.008). Baseline TNF-α did not predict cognitive decline, and hs-CRP did not predict cognitive performance or decline after 10-years.
Our results suggest that low-grade inflammation in midlife is an independent risk factor for poorer cognitive performance later in life. Of the studied markers, IL-6 and TNF-α seem to be stronger predictors for cognitive performance and decline than hs-CRP.
CADASIL and CARASIL Tikka, Saara; Baumann, Marc; Siitonen, Maija ...
Brain pathology (Zurich, Switzerland),
September 2014, Letnik:
24, Številka:
5
Journal Article
Recenzirano
Odprti dostop
CADASIL and CARASIL are hereditary small vessel diseases leading to vascular dementia. CADASIL commonly begins with migraine followed by minor strokes in mid‐adulthood. Dominantly inherited CADASIL ...is caused by mutations (n > 230) in NOTCH3 gene, which encodes Notch3 receptor expressed in vascular smooth muscle cells (VSMC). Notch3 extracellular domain (N3ECD) accumulates in arterial walls followed by VSMC degeneration and subsequent fibrosis and stenosis of arterioles, predominantly in cerebral white matter, where characteristic ischemic MRI changes and lacunar infarcts emerge. The likely pathogenesis of CADASIL is toxic gain of function related to mutation‐induced unpaired cysteine in N3ECD. Definite diagnosis is made by molecular genetics but is also possible by electron microscopic demonstration of pathognomonic granular osmiophilic material at VSMCs or by positive immunohistochemistry for N3ECD in dermal arteries.
In rare, recessively inherited CARASIL the clinical picture and white matter changes are similar as in CADASIL, but cognitive decline begins earlier. In addition, gait disturbance, low back pain and alopecia are characteristic features. CARASIL is caused by mutations (presently n = 10) in high‐temperature requirement. A serine peptidase 1 (HTRA1) gene, which result in reduced function of HTRA1 as repressor of transforming growth factor‐β (TGF β) ‐signaling. Cerebral arteries show loss of VSMCs and marked hyalinosis, but not stenosis.
Autosomal-dominant Alzheimer's disease (ADAD) may be associated with atypical amyloid beta deposits in the brain. In vivo amyloid imaging using
C-Pittsburgh compound B (PiB) tracer has shown ...differences in binding between brains from ADAD and sporadic Alzheimer's disease (sAD) patients. To gain further insight into the various pathological characteristics of these genetic variants, we performed large frozen hemisphere autoradiography and brain homogenate binding assays with
H-PiB,
H-MK6240-
H-THK5117, and
H-deprenyl for detection of amyloid fibrils, tau depositions, and activated astrocytes, respectively, in two AβPParc mutation carriers, one PSEN1ΔE9 mutation carrier, and three sAD cases. The results were compared with Abeta 40, Abeta 42, AT8, and GFAP immunostaining, respectively, as well as with Congo red and Bielschowsky. PiB showed a very low binding in AβPParc. A high binding was observed in PSEN1ΔE9 and in sAD tissues but with different binding patterns. Comparable
H-THK5117 and
H-deprenyl brain homogenate binding was observed for AβPParc, PSEN1ΔE9, and sAD, respectively. Some differences were observed between
H-MK6240 and
H-THK5117 in ADAD. A positive correlation between
H-deprenyl and
H-THK5117 binding was observed in AβPParc, while no such correlation was found in PSEN1ΔE9 and sAD. Our study demonstrates differences in the properties of the amyloid plaques between two genetic variants of AD and sAD. Despite the lack of measurable amyloid fibrils by PiB in the AβPParc cases, high regional tau and astrocyte binding was observed. The lack of correlation between
H-deprenyl and
H-THK5117 binding in PSEN1ΔE9 and sAD in contrast of the positive correlation observed in the AβPParc cases suggest differences in the pathological cascade between variants of AD that warrant further exploration in vivo.
Background
In clinical practice, there is a need for an instrument to screen older people at risk of institutionalization.
Aims
To analyze the association of frailty, walking-ability and self-rated ...health (SRH) with institutionalization in Finnish community-dwelling older people.
Methods
In this prospective study with 10- and 18-year follow-ups, frailty was assessed using FRAIL Scale (FS) (
n
= 1087), Frailty Index (FI) (
n
= 1061) and PRISMA-7 (
n
= 1055). Walking ability was assessed as self-reported ability to walk 400 m (
n
= 1101). SRH was assessed by a question of general SRH (
n
= 1105). Cox regression model was used to analyze the association of the explanatory variables with institutionalization.
Results
The mean age of the participants was 73.0 (range 64.0‒97.0) years. Prevalence of institutionalization was 40.8%. In unadjusted models, frailty was associated with a higher risk of institutionalization by FS in 10-year follow-up, and FI in both follow-ups. Associations by FI persisted after age- and gender-adjustments in both follow-ups. By PRISMA-7, frailty predicted a higher risk of institutionalization in both follow-ups. In unadjusted models, inability to walk 400 m predicted a higher risk of institutionalization in both follow-ups and after adjustments in 10-year follow-up. Poor SRH predicted a higher risk of institutionalization in unadjusted models in both follow-ups and after adjustments in 10-year follow-up.
Discussion
Simple self-reported items of walking ability and SRH seemed to be comparable with frailty indexes in predicting institutionalization among community-dwelling older people in 10-year follow-up.
Conclusions
In clinical practice, self-reported walking ability and SRH could be used to screen those at risk.
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient ...therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls. AD astrocytes manifest hallmarks of disease pathology, including increased β-amyloid production, altered cytokine release, and dysregulated Ca2+ homeostasis. Furthermore, due to altered metabolism, AD astrocytes show increased oxidative stress and reduced lactate secretion, as well as compromised neuronal supportive function, as evidenced by altering Ca2+ transients in healthy neurons. Our results reveal an important role for astrocytes in AD pathology and highlight the strength of iPSC-derived models for brain diseases.
•PSEN1 mutant AD astrocytes manifest hallmarks of AD pathology•Altered mitochondrial metabolism in AD astrocytes increases oxidative stress•AD astrocytes reduce the calcium signaling activity of healthy neurons•Astrocytes are important in the pathogenesis of AD
In this article, Koistinaho and colleagues reveal that astrocytes from PSEN1 ΔE9 patients display a severe AD-related phenotype, including increased Aβ production, altered mitochondrial metabolism, and reduced lactate secretion. Furthermore, PSEN1 ΔE9 astrocytes influence the calcium signaling activity of healthy neurons. The results highlight the importance of astrocytes in AD pathogenesis.
Physical activity may help maintain cognitive function and decrease dementia risk, but epidemiological findings remain controversial. The aim of our study was to investigate the association between ...leisure-time physical activity at midlife and the subsequent development of dementia and Alzheimer's disease (AD).
Participants were randomly selected from the survivors of a population-based cohort previously surveyed in 1972, 1977, 1982, or 1987. 1449 persons (72·5%) age 65–79 years participated in the re-examination in 1998 (mean follow-up, 21 years). 117 persons had dementia and 76 had AD. Multiple logistic regression methods were used to analyse the association between leisure-time physical activity and dementia or AD.
Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD (odds ratio OR 0·48 95% CI 0·25–0·91 and 0·38 0·17–0·85, respectively), even after adjustments for age, sex, education, follow-up time, locomotor disorders,
APOE genotype, vascular disorders, smoking, and alcohol drinking. The associations were more pronounced among the
APOE ɛ4 carriers.
Leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life. Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals.
We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and ...neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß1-42, total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD.
PDF
