Midlife insulin resistance, APOE genotype, and change in late-life brain beta-amyloid accumulation - A 5-year follow-up [11C]PIB-PET study.

We studied if midlife insulin resistance (IR) and APOE genotype would predict brain beta-amyloid (Aß) accumulation and Aß change in late-life in 5-year follow-up [11C]PIB-PET study. 43 dementia-free participants were scanned twice with [11C]PIB-PET in their late-life (mean age at follow-up 75.4 years). Participants were recruited from the Finnish Health2000 study according to their HOMA-IR values measured in midlife (mean age at midlife 55.4 years; IR+ group, HOMA-IR > 2.17; IR- group, HOMA-IR <1.25), and their APOEε4 genotype. At late-life follow-up, [11C]PIB-PET composite SUVr was significantly higher in IR+ group than IR- group (median 2.3 (interquartile range 1.7-3.3) vs. 1.7 (1.5-2.4), p = 0.03). There was no difference between IR- and IR+ groups in [11C]PIB-PET SUVr 5-year change, but the change was significantly higher in IR+/APOEε4+ group (median change 0.8 (0.60-1.0)) than in IR-/APOEε4- (0.28 (0.14-0.47), p = 0.02) and in IR+/APOEε4- group (0.24 (0.06-0.40), p = 0.046). These results suggest that APOEε4 carriers with midlife IR are at increased risk for late-life Aß accumulation.

AEGIS-AcutE Geriatric Intervention Study: pilot study of frontline acute geriatric assessment to improve quality of care in emergency department.

INTRODUCTION: Due to the increasing number of older patients in emergency departments (EDs) with frailty, cognitive impairment and multimorbidity, there is a need for geriatric expertise in EDs. METHODS: This retrospective study is of older patients visiting Turku University Hospital ED between 2 January and 31 December 2022. Patients aged 75 years of older were screened for frailty using Triage Risk Screening Tool (TRST) and Clinical Frailty Scale (CFS). Nonacute, frail patients (CFS ≥4) suitable for Targeted Geriatric Assessment (TGA) (n = 1096) were scanned for the risk of delirium, cognitive impairment, change in functional status, falls, malnutrition and depression. A comprehensive patient record was made with recommendations for future care. RESULTS: TRST was completed in 70% of the ED visits, and two-thirds of those were considered high-risk. Among the patients assessed by the geriatric team (TGA), nonspecific complaint (38%) and falls (35%) were the main reasons for ED admission. Cognitive impairment was present in over 60% and orthostatic hypotension in 40% of the patients. The 72-hour revisit rate for TGA-patients was 2.3%. For the real-life control group, the 72-hour revisit rate was 4.6% (P = .001). Thirty-day revisit rates were 10% and 16%, respectively (P < .001). The need for rehabilitation, cognitive evaluation and intensifying home care were the main recommendations for future care. CONCLUSIONS: TGA approach provides structured and accurate information on older patients' background. This may lead to more precise diagnostics, a thorough consideration of hospital intake and a secure discharge from the ED. Ensuring continuity of care may help to reduce readmissions to EDs.

Predicting successful ageing among older adults seems possible even as far as two decades ahead.

BACKGROUND: Successful ageing is the term often used for depicting exceptional ageing and can be measured with multidimensional models including physical, psychological and social wellbeing. The aim of this study was to test multidimensional successful ageing models to investigate whether these models can predict successful ageing, and which individual subcomponents included in the models are most significantly associated with successful ageing. METHODS: Successful ageing was defined as the ability to live at home without daily care at the age of 84 years or over. Data on the participants' physical, psychological and social wellbeing were gathered at baseline and the follow-up period was 20 years. Four successful ageing models were constructed. Backward stepwise logistic regression analysis was used to identify the individual subcomponents of the models which best predicted successful ageing. RESULTS: All successful ageing models were able to predict ageing successfully after the 20-year follow-up period. After the backward stepwise logistic regression analysis, three individual subcomponents of four models remained statistically significant and were included in the new model: having no heart disease, having good self-rated health and feeling useful. As a model, using only these three subcomponents, the association with successful ageing was similar to using the full models. CONCLUSIONS: Multidimensional successful ageing models were able to predict successful ageing after a 20-year follow-up period. However, according to the backward stepwise logistic regression analysis, the three subcomponents (absence of heart disease, good self-rated health and feeling useful) significantly associated with successful ageing performed as well as the multidimensional successful ageing models in predicting ageing successfully.

The natural history of hypertension in older adults: a study of two Finnish generational cohorts born 20 years apart.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

We studied two generational cohorts of older adults from Finland, born 20 years apart, to examine changes in blood pressure readings over time, the prevalence of high blood pressure, and its treatment. Our investigation spanned periods both before and after the HYVET Study, a significant research effort demonstrating the benefits of treating hypertension in older adult patients, reducing the risk of stroke and other causes of mortality. Additionally, we considered the potential impact of the COVID-19 pandemic on blood pressure control.We invited all 70-year-olds living at home in Turku, Southwest Finland, to participate in our survey in 1990 (the 1920-born cohort) and in 2010 (the 1940-born cohort), with plans to follow them for 25 years. We collected data on their blood pressure readings and the medications they were prescribed.At the outset of our study, when participants were 70 years old, a higher proportion of individuals in the 1920-born cohort had uncontrolled high blood pressure compared to those in the 1940-born group. In addition, the participants born in 1940 showed increased usage and a wider selection of antihypertensive medications compared to the 1920-born cohort. Despite this, over 70% of the 70-year-olds even in the 1940-born cohort still had uncontrolled blood pressure. Furthermore, by the time these individuals reached their early 80s, the initial improvements in blood pressure control over the 1920-born cohort had somewhat diminished.Our findings underscore the ongoing need for improvements in managing high blood pressure among older adults. This remains crucial as individuals age, emphasising the importance of continued research to develop better treatment approaches, even after landmark studies like HYVET.

Trends in Positive Life Orientation Among 70-Year-Olds: A Comparison of Two Finnish Cohorts Born 20 Years Apart.

OBJECTIVES: We assessed if positive life orientation (PLO) has increased among older individuals and explored gender disparities in PLO changes. METHODS: Two cohorts of 70-year-olds from Turku, Finland were included: the 1920 birth cohort (examined in 1991; n = 1,032) and the 1940 birth cohort (examined in 2011; n = 956). Participants completed an identical questionnaire assessing life satisfaction, feeling needed, future plans, zest for life, depression, and loneliness. A composite PLO score (range 0-1) was computed. RESULTS: The 2011 cohort had a higher mean PLO score than the 1991 cohort (.87 vs. .83, p < .001). The 2011 cohort reported higher sense of being needed, more future plans, and reduced loneliness (all p < .001). No significant differences were found in life satisfaction, zest for life, or depression. Gender disparities in PLO persisted across both cohorts, with men scoring slightly higher but following similar trends as women. DISCUSSION: PLO appears to have increased among older individuals. CLINICAL IMPLICATIONS: Recognizing the rising trend of PLO in recent decades may influence the development of societal and healthcare policies to further improve overall well-being among older individuals.

Re-examination of successful agers with lower biological than chronological age still after a 20-year follow-up period.

BACKGROUND: Successful ageing is the term often used for depicting exceptional ageing but a uniform definition is lacking. The aim was to re-examine and describe the successful agers living at home at the age of 84 years or over after a 20-year follow-up. The purpose was also to identify possible factors leading to their successful ageing. METHODS: Successful ageing was defined as the ability to live at home without daily care. Data on the participants' functional ability, objective health, self-rated health and satisfaction with life were gathered at baseline and after a 20-year follow-up period. A measurement of personal biological age (PBA) was established and the difference between the PBA and the chronological age (CA) was counted. RESULTS: The participants' mean age was 87.6 years (Standard deviation 2.5, range 84-96). All analyzed variables depicted poorer physical ability and subjective health at re-examination than at baseline. Still, 99% of the participants were at least moderately satisfied with their lives. The PBA at baseline was 6.5 years younger than CA, and at re-examination, the difference was even more pronounced at 10.5 years. DISCUSSION: Even though the participants were chronologically older, had poorer physical ability and subjective health, they were still satisfied with their lives indicating possible psychological resilience. The difference between the PBA and CA was greater at re-examination than at baseline indicating that they were also biologically successful agers. CONCLUSIONS: Successful agers were satisfied with life despite hardships and had a lower biological than chronological age. Further research is needed to evaluate causality.

A novel easy-to-use index to predict institutionalization and death in older population - a 10-year population-based follow-up study.

BACKGROUND: Various indexes have been developed to estimate the risk for mortality, institutionalization, and other adverse outcomes for older people. Most indexes are based on a large number of clinical or laboratory parameters. An index based on only a few parameters would be more practical to use in every-day clinical practice. Our aim was to create an index to predict the risk for mortality and institutionalization with as few parameters as possible without compromising their predictive ability. METHODS: A prospective study with a 10-year follow-up period. Thirty-six clinical and fourteen laboratory parameters were combined to form an index. Cox regression model was used to analyze the association of the index with institutionalization and mortality. A backward statistical method was used to reduce the number of parameters to form an easy-to-use index for predicting institutionalization and mortality. RESULTS: The mean age of the participants (n = 1172) was 73.1 (SD 6.6, range 64‒97) years. Altogether, 149 (14%) subjects were institutionalized, and 413 (35%) subjects deceased during the follow-up. Institutionalization and mortality rates increased as index scores increased both for the large 50-parameter combined index and for the reduced indexes. After a backward variable selection in the Cox regression model, three clinical parameters remained in the index to predict institutionalization and six clinical and three laboratory parameters in the index to predict mortality. The reduced indexes showed a slightly better predictive value for both institutionalization and mortality compared to the full index. CONCLUSIONS: A large index with fifty parameters included many unimportant parameters that did not increase its predictive value, and therefore could be replaced with a reduced index with only a few carefully chosen parameters, that were individually associated with institutionalization or death.

Senior Health Clinic for 75-year-old home-dwelling Finns - study design, clinic protocol and non-response analysis.

BACKGROUND: In the Finnish policy on older people preventive activities, which maintain functional capacity and independent living, are emphasized. The Turku Senior Health Clinic, aimed at maintaining independent coping of all home-dwelling 75-year-old citizens in the city of Turku, was founded in the beginning of 2020. The aim of this paper is to describe design and protocol of the Turku Senior Health Clinic Study (TSHeC) and provide results of the non-response analysis. METHODS: The non-response analysis used data from 1296 participants (71% of those eligible) and 164 non-participants of the study. Sociodemographic, health status, psychosocial and physical functional ability indicators were included in the analysis. Participants and non-participants were also compared in respect to their neighborhood socioeconomic disadvantage. Differences between participants and non-participants were tested using the Chi squared or Fisher´s exact test for categorical variables and t-test for continuous variable. RESULTS: The proportions of women (43% vs. 61%) and of those with only satisfying, poor or very poor self-rated financial status (38% vs. 49%) were significantly lower in non-participants than in participants. Comparison of the non-participants and participants in respect to their neighborhood socioeconomic disadvantage showed no differences. The prevalence of hypertension (66% vs. 54%), chronic lung disease (20% vs. 11%), and kidney failure (6% vs. 3%) were higher among non-participants compared to participants. Feelings of loneliness were less frequent among non-participants (14%) compared to participants (32%). The proportions of those using assistive mobility devices (18% vs. 8%) as well as those having previous falls (12% vs. 5%) were higher in non-participants than in participants. CONCLUSIONS: The participation rate of TSHeC was high. No neighborhood differences in participation were found. Health status and physical functioning of non-participants seemed to be slightly worse than those of the participants, and more women than men participated. These differences may weaken the generalizability of the findings of the study. The differences have to be taken into account when recommendation for the content and implementation of preventive nurse-managed health clinic in primary health care in Finland is going to be given. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05634239; registration date; 1st of December 2022. Retrospectively registered.

Amyloid, tau, and astrocyte pathology in autosomal-dominant Alzheimer's disease variants: AßPParc and PSEN1DE9.

Autosomal-dominant Alzheimer's disease (ADAD) may be associated with atypical amyloid beta deposits in the brain. In vivo amyloid imaging using 11C-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 3H-PiB, 3H-MK6240-3H-THK5117, and 3H-deprenyl for detection of amyloid fibrils, tau depositions, and activated astrocytes, respectively, in two AßPParc 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 AßPParc. A high binding was observed in PSEN1ΔE9 and in sAD tissues but with different binding patterns. Comparable 3H-THK5117 and 3H-deprenyl brain homogenate binding was observed for AßPParc, PSEN1ΔE9, and sAD, respectively. Some differences were observed between 3H-MK6240 and 3H-THK5117 in ADAD. A positive correlation between 3H-deprenyl and 3H-THK5117 binding was observed in AßPParc, 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 AßPParc cases, high regional tau and astrocyte binding was observed. The lack of correlation between 3H-deprenyl and 3H-THK5117 binding in PSEN1ΔE9 and sAD in contrast of the positive correlation observed in the AßPParc cases suggest differences in the pathological cascade between variants of AD that warrant further exploration in vivo.

The long-term prognostic value of serum 25(OH)D, albumin, and LL-37 levels in acute respiratory diseases among older adults.

BACKGROUND: Older adults are more susceptible to respiratory tract infection than healthy working age adults. The increased susceptibility of older adults is thought to be interlinked with vitamin D status, nourishment, and immunological state in general. Data are scarce whether these parameters could serve as prognostic markers. AIM: To study whether serum 25(OH)D, albumin, and LL-37 level could give prognostic value of long-term survival in the older adults with multimorbidity and acute respiratory infection. METHODS: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory markers included serum levels of 25(OH)D, albumin and LL-37, C-reactive protein (CRP), white blood cell count (WBC) and polymerase chain reaction diagnostics for 14 respiratory viruses. Pneumonia was confirmed by chest radiographs. Respiratory illness severity, death at ward, length of hospital stays, and 5-year survival were used as outcomes. RESULTS: In total, 289 older adult patients with mean age of 83 years were included in the study. Serum 25(OH)D deficiency (< 50 nmol/liter) was present in 59% and hypoalbuminemia (< 3.5 g/dL) in 55% of the study patients. Low serum albumin level was associated to one, two- and five-year mortality after hospital stay (all P < .05). In addition, it was associated with pneumonia, dyspnea, over 13-night long stay at ward and death at ward (all P < .05). No associations were seen between serum 25(OH)D and LL-37 levels and disease severity, short-term clinical outcome, or long-term survival. Associations between serum 25(OH)D, albumin, and LL-37 levels and respiratory virus presence were not seen. CONCLUSIONS: Serum albumin level on admission seems to give valuable information about the patients' general health and recovery potential in treating older adults with respiratory symptoms. Serum 25(OH)D and LL-37 had no associations with disease severity or long- and short-term prognosis among older adults hospitalized with respiratory symptoms.

Prevalence and prognostic significance of depressive symptoms in a geriatric post-hip fracture assessment.

OBJECTIVES: To investigate the prevalence and prognostic significance of post-hip fracture depressive symptoms. METHODS: A naturalistic clinical cohort study. Data were collected on admission to hospital, geriatric assessment 4-6 months post-fracture and by telephone interview one-year post fracture. Depressive symptoms were assessed at the geriatric assessment using the 15-item Geriatric Depression Scale (GDS-15). Logistic regression analyses with multivariable models were conducted to examine the association of depressive symptoms with changes in mobility and living arrangements and Cox proportional hazards models for mortality between the geriatric assessment and one-year follow-up. RESULTS: Of the 1070 patients, 22% (n = 238) had mild and 6% (n = 67) moderate to severe depressive symptoms. Patients with depressive symptoms had poorer nutritional status at baseline, lower scores on the cognitive and physical performance tests and poorer functional abilities in the geriatric assessment than those without. No association was observed between depressive symptoms and any of the outcomes at one-year follow-up. Poor nutritional status and physical functioning remained significant prognostic indicators. CONCLUSION: Post-hip fracture depressive symptoms are common and deserve attention during post-hip fracture recovery and rehabilitation. Nonetheless, depressive symptoms have no impact on the change in mobility or living arrangements or mortality. These latter outcomes are mainly explained by poor nutritional status and functioning.

The Association of the Brief Dementia Risk Index and Incident Dementia among Finnish 70-Year-Olds: A 5-Year Follow-Up Study.

BACKGROUND: An accurate identification of older individuals at increased risk of developing dementia is very important. Various dementia risk prediction models have been developed, but not all models are applicable among older population. OBJECTIVES: To examine the association of the Brief Dementia Risk Index (BDRI) and incidence of dementia among community-dwelling Finnish older adults. METHODS: Participants were community-dwelling nondemented 70-year-olds examined in 2011 (n = 943). Cox regression model with death as a competing risk was used to analyze the association of BDRI and incident dementia (ICD-10 codes F00-03 and G30) during the 5-year follow-up (n = 883). RESULTS: The rate of dementia incidence was 4.9% during the follow-up. Having at least moderate risk according to BDRI significantly predicted incident dementia (hazard ratio 3.18, 95% confidence interval: 1.71-5.92, p < 0.001), also after adjustment with education level (2.93, 1.52-5.64, p = 0.001). No interaction between gender and BDRI was found. CONCLUSION: BDRI could be an applicable tool for identification of older individuals at increased risk of developing dementia in clinical settings.

A practical laboratory index to predict institutionalization and mortality - an 18-year population-based follow-up study.

BACKGROUND: Previously, several indexes based on a large number of clinical and laboratory tests to predict mortality and frailty have been produced. However, there is still a need for an easily applicable screening tool for every-day clinical practice. METHODS: A prospective study with 10- and 18-year follow-ups. Fourteen common laboratory tests were combined to an index. Cox regression model was used to analyse the association of the laboratory index with institutionalization and mortality. RESULTS: The mean age of the participants (n = 1153) was 73.6 (SD 6.8, range 64.0-100.0) years. Altogether, 151 (14.8%) and 305 (29.9%) subjects were institutionalized and 422 (36.6%) and 806 (69.9%) subjects deceased during the 10- and 18-year follow-ups, respectively. Higher LI (laboratory index) scores predicted increased mortality. Mortality rates increased as LI scores increased both in unadjusted and in age- and gender-adjusted models during both follow-ups. The LI did not significantly predict institutionalization either during the 10- or 18-year follow-ups. CONCLUSIONS: A practical index based on routine laboratory tests can be used to predict mortality among older people. An LI could be automatically counted from routine laboratory results and thus an easily applicable screening instrument in clinical settings.

Subjective and objective health predicting mortality and institutionalization: an 18-year population-based follow-up study among community-dwelling Finnish older adults.

BACKGROUND: Objective health measures, such as registered illnesses or frailty, predict mortality and institutionalization in older adults. Also, self-reported assessment of health by simple self-rated health (SRH) has been shown to predict mortality and institutionalization. The aim of this study was to assess the association of objective and subjective health with mortality and institutionalization in Finnish community-dwelling older adults. METHODS: In this prospective study with 10- and 18-year follow-ups, objective health was measured by registered illnesses and subjective health was evaluated by simple SRH, self-reported walking ability (400 m) and self-reported satisfaction in life. The participants were categorized into four groups according to their objective and subjective health: 1. subjectively and objectively healthy, 2. subjectively healthy and objectively unhealthy, 3. subjectively unhealthy and objectively healthy and 4. subjectively and objectively unhealthy. Cox regression model was used in the analyses. Death was used as a competing factor in the institutionalization analyses. RESULTS: The mean age of the participants (n = 1259) was 73.5 years (range 64.0-100.0). During the 10- and 18-year follow-ups, 466 (37%) and 877 (70%) died, respectively. In the institutionalization analyses (n = 1106), 162 (15%) and 328 (30%) participants were institutionalized during the 10- and 18-year follow-ups, respectively. In both follow-ups, being subjectively and objectively unhealthy, compared to being subjectively and objectively healthy, was significantly associated with a higher risk of institutionalization in unadjusted models and with death both in unadjusted and adjusted models. CONCLUSIONS: The categorization of objective and subjective health into four health groups was good at predicting the risk of death during 10- and 18-year follow-ups, and seemed to also predict the risk of institutionalization in the unadjusted models during both follow-ups. Poor subjective health had an additive effect on poor objective health in predicting mortality and could therefore be used as part of an older individual's health evaluation when screening for future adverse outcomes.

Frailty, walking ability and self-rated health in predicting institutionalization: an 18-year follow-up study among Finnish community-dwelling older people.

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.

NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes.

Alzheimer's disease (AD) is a common dementia affecting a vast number of individuals and significantly impairing quality of life. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for AD. Astrocytes, the most common cell type of the central nervous system, have been shown to play a role in the major AD pathologies, including accumulation of amyloid plaques, neuroinflammation, and oxidative stress. Here, we show that inflammatory stimulation leads to metabolic activation of human astrocytes and reduces amyloid secretion. On the other hand, the activation of oxidative metabolism leads to increased reactive oxygen species production especially in AD astrocytes. While healthy astrocytes increase glutathione (GSH) release to protect the cells, Presenilin-1-mutated AD patient astrocytes do not. Thus, chronic inflammation is likely to induce oxidative damage in AD astrocytes. Activation of NRF2, the major regulator of cellular antioxidant defenses, encoded by the NFE2L2 gene, poses several beneficial effects on AD astrocytes. We report here that the activation of NRF2 pathway reduces amyloid secretion, normalizes cytokine release, and increases GSH secretion in AD astrocytes. NRF2 induction also activates the metabolism of astrocytes and increases the utilization of glycolysis. Taken together, targeting NRF2 in astrocytes could be a potent therapeutic strategy in AD.

Self-rated health and objective health status as predictors of all-cause mortality among older people: a prospective study with a 5-, 10-, and 27-year follow-up.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Secular changes in dementia risk indices among 70-year-olds: a comparison of two Finnish cohorts born 20 years apart.

AIMS: To compare dementia risk indices among two separate cohorts of 70-year-olds born 20 year apart. METHODS: Community-dwelling 70-year-old Finns were examined with similar examinations in 1991 (n = 1032) and in 2011 (n = 960). Dementia risk was assessed with the CAIDE Dementia Risk Score (CAIDE) (n = 1516), the Brief Dementia Risk Index (BDRI) (n = 1598) and the Dementia Screening Indicator (DSI) (n = 1462). RESULTS: The proportion of subjects with moderate or high risk for dementia was significantly higher in earlier than in later born cohort according to CAIDE (99% and 94%, respectively, p < 0.001) and BDRI (41% and 15%, p < 0.001), but not according to DSI (5% and 6%, p = 0.184). The total scores of the earlier born cohort were significantly higher than those of the later born cohort according to all three indices. CONCLUSIONS: According to dementia risk indices, it seems that dementia risk has decreased among community-dwelling 70-year-old subjects during the last decades in Finland.

Respiratory tract virus infections in the elderly with pneumonia.

BACKGROUND: In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia. METHODS: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints. RESULTS: Median age of the patients was 83 years (range 76-90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 109/L (P = .006) and a CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and symptoms or prognosis of radiographically-verified pneumonia episodes. CONCLUSION: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with pneumonia outside the epidemic seasons.

Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGFß expression.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial fatal progressive degenerative disorder. One of the pathological hallmarks of CADASIL is a dramatic reduction of vascular smooth muscle cells (VSMCs) in cerebral arteries. Using VSMCs from the vasculature of the human umbilical cord, placenta and cerebrum of CADASIL patients, we found that CADASIL VSMCs had a lower proliferation rate compared to control VSMCs. Exposure of control VSMCs and endothelial cells (ECs) to media derived from CADASIL VSMCs lowered the proliferation rate of all cells examined. By quantitative RT-PCR analysis, we observed increased Transforming growth factor-ß (TGFß) gene expression in CADASIL VSMCs. Adding TGFß-neutralizing antibody restored the proliferation rate of CADASIL VSMCs. We assessed proliferation differences in the presence or absence of TGFß-neutralizing antibody in ECs co-cultured with VSMCs. ECs co-cultured with CADASIL VSMCs exhibited a lower proliferation rate than those co-cultured with control VSMCs, and neutralization of TGFß normalized the proliferation rate of ECs co-cultured with CADASIL VSMCs. We suggest that increased TGFß expression in CADASIL VSMCs is involved in the reduced VSMC proliferation in CADASIL and may play a role in situ in altered proliferation of neighbouring cells in the vasculature.