Blood pressure in dementia, mild cognitive impairment, and subjective cognitive decline related to time of death

Objective: It is unknown whether systolic blood pressure (SBP) drop is part of the normal aging process or due to the onset of dementia for some people. SBP drop is referring to the decrease in blood pressure often seen before death. Thus, the aim of this study was to examine whether SBP at time of diagnosis of dementia, mild cognitive impairment, or subjective cognitive decline was associated with years prior to death, and whether these associations were modified by diagnoses, age, and sex. Methods: Participants were 2,236 patients from the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog), who died during follow-up (2009-2017) for whom we had valid blood pressure measurements. Mean age at diagnosis was 77.5 years (SD 8.3), and patients were followed for an average of 3.9 years (SD 2.2, maximum 10.5 years). The patients had subjective cognitive decline (95), mild cognitive impairment (573), dementia (1,401), or no diagnoses related to cognitive deficits (167). SBP as dependent variable was regressed against years prior to death. Results: In men, SBP was 1.8 mmHg lower per year closer to death (p < .01), and this trend was linear without any acceleration. This association between years prior to death and SBP in men was not modified by age, year of diagnosis, or diagnosis. There was no such association in women. Conclusion: SBP was significantly lower for those diagnosed close to death in men, but not in women. This association was not modified by either age or onset of diagnosis. Thus, the lowering of SBP is more related to closeness to death and sex than to dementia or age. The downward trend was linear all 10 years prior to death, with no acceleration closer to death.publishedVersio

Blood Pressure in Different Dementia Disorders, Mild Cognitive Impairment, and Subjective Cognitive Decline

The aim of the study was to investigate whether blood pressure (BP) differed among people with different dementia diagnoses, mild cognitive impairment, and subjective cognitive decline and whether BP differences were observed across age and sex. Our study population comprised clinical data from 6,236 patients (53.5% women) aged 45–97 years (Mean = 73.9, SD = 9.6) referred to dementia assessment in 42 outpatient clinics across Norway during 2009–2019. Patients with the following diagnoses were included: Subjective cognitive decline (SCD), Mild cognitive impairment (MCI), dementia due to Alzheimer’s disease (AD), Vascular dementia (VaD), mixed AD and VaD, and dementia in Parkinson’s disease/Lewy body disease (PDD/LBD). For all diagnostic groups, SBP increased with age until about 80 years, after which it trended downward, whereas DBP declined after 60 years of age for all diagnostic groups. Patients aged 65 years and younger with SCD had lower SBP compared to AD patients at the same age, but SBP increased rapidly with increasing age, resulting in a substantially higher SBP at 80 + years compared with all other diagnostic groups. No other differences in SBP or diastolic blood pressure (DBP) were found among patients with the different dementia diagnosis. Neither SBP nor DBP differed between MCI and AD groups. An interaction between age and gender was found for SBP at younger ages, as women started out with a lower pressure than men did but ended up with higher SBP. Conclusion: Among 80+ patients, blood pressure did not differ as a function of the various dementia disorders. The SBP for the SCD patients of various age groups differed from all other diagnostic groups, indicating either that internal regulation of BP in older people is a risk factor for dementia or that brain damage causing dementia or MCI may led to changes in blood pressure. Brain aging seems to influence SBP differently in men and womenpublishedVersio

Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status

The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied.publishedVersio

Regression models for linking patterns of growth to a later outcome:Infant growth and childhood overweight

Abstract Background Regression models are widely used to link serial measures of anthropometric size or changes in size to a later outcome. Different parameterisations of these models enable one to target different questions about the effect of growth, however, their interpretation can be challenging. Our objective was to formulate and classify several sets of parameterisations by their underlying growth pattern contrast, and to discuss their utility using an expository example. Methods We describe and classify five sets of model parameterisations in accordance with their underlying growth pattern contrast (conditional growth; being bigger v being smaller; becoming bigger and staying bigger; growing faster v being bigger; becoming and staying bigger versus being bigger). The contrasts are estimated by including different sets of repeated measures of size and changes in size in a regression model. We illustrate these models in the setting of linking infant growth (measured on 6 occasions: birth, 6 weeks, 3, 6, 12 and 24 months) in weight-for-height-for-age z-scores to later childhood overweight at 8y using complete cases from the Norwegian Childhood Growth study (n = 900). Results In our expository example, conditional growth during all periods, becoming bigger in any interval and staying bigger through infancy, and being bigger from birth were all associated with higher odds of later overweight. The highest odds of later overweight occurred for individuals who experienced high conditional growth or became bigger in the 3 to 6 month period and stayed bigger, and those who were bigger from birth to 24 months. Comparisons between periods and between growth patterns require large sample sizes and need to consider how to scale associations to make comparisons fair; with respect to the latter, we show one approach. Conclusion Studies interested in detrimental growth patterns may gain extra insight from reporting several sets of growth pattern contrasts, and hence an approach that incorporates several sets of model parameterisations. Co-efficients from these models require careful interpretation, taking account of the other variables that are conditioned on

Comparing associations of handgrip strength and chair stand performance with all-cause mortality—implications for defining probable sarcopenia: the Tromsø Study 2015–2020

Background Widely adopted criteria suggest using either low handgrip strength or poor chair stand performance to identify probable sarcopenia. However, there are limited direct comparisons of these measures in relation to important clinical endpoints. We aimed to compare associations between these two measures of probable sarcopenia and all-cause mortality. Methods Analyses included 7838 community-dwelling participants (55% women) aged 40–84 years from the seventh survey of the Tromsø Study (2015–2016), with handgrip strength assessed using a Jamar + Digital Dynamometer and a five-repetition chair stand test (5-CST) also undertaken. We generated sex-specific T-scores and categorised these as “not low”, “low”, and “very low” handgrip strength or 5-CST performance. Cox Proportional Hazard regression models were used to investigate associations between these two categorised performance scores and time to death (up to November 2020 ascertained from the Norwegian Cause of Death registry), adjusted for potential confounders including lifestyle factors and specific diseases. Results A total of 233 deaths occurred (median follow-up 4.7 years) with 1- and 5-year mortality rates at 3.1 (95% confidence interval [CI] 2.1, 4.6) and 6.3 (95% CI 5.5, 7.2) per 1000 person-years, respectively. There was poor agreement between the handgrip strength and 5-CST categories for men (Cohen’s kappa [κ] = 0.19) or women (κ = 0.20). Fully adjusted models including handgrip strength and 5-CST performance mutually adjusted for each other, showed higher mortality rates among participants with low (hazard ratio [HR] 1.22, 95% CI 0.87, 1.71) and very low (HR 1.68, 95% CI 1.02, 2.75) handgrip strength compared with the not low category. Similar associations, although stronger, were seen for low (HR 1.88, 95% CI 1.38, 2.56) and very low (HR 2.64, 95% CI 1.73, 4.03) 5-CST performance compared with the not low category. Conclusions We found poor agreement between T-score categories for handgrip strength and 5-CST performance and independent associations with mortality. Our findings suggest that these tests identify different people at risk when case-finding probable sarcopenia. As discussions on an international consensus for sarcopenia definitions proceed, testing both handgrip strength and chair stand performance should be recommended rather than viewing these as interchangeable assessments

Hand grip strength and risk of incident venous thromboembolism: The Tromsø study

Background Hand grip strength (HGS), a common proxy of whole-body muscular strength, is associated with a wide range of adverse health outcomes and mortality. However, there are limited data on the association between HGS and risk of venous thromboembolism (VTE). Objectives We aimed to investigate the association between HGS and risk of incident VTE in a population-based cohort. Methods Participants (n = 13,704) from the fourth to seventh surveys of the Tromsø study (Tromsø4–Tromsø7, enrollment: 1994–2016) were followed throughout 2020, and all incident VTEs were recorded. HGS of the nondominant hand was measured using a Martin Vigorimeter (Tromsø4–Tromsø6) and a Jamar Digital Dynamometer (Tromsø7). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) according to weak HGS (less than 25th percentile) versus normal HGS (25th percentile or greater) were estimated using Cox regression models and adjusted for age, sex, body height, body mass index, physical activity, cardiovascular disease, and cancer. Results During a median of 6.5 years of follow-up, 545 incident VTEs occurred. Participants with weak HGS had a 27% higher risk of VTE (HR, 1.27; 95% CI, 1.03–1.57) compared to those with normal HGS. Subgroup analyses revealed that the point estimates were higher for unprovoked VTE (HR, 1.35; 95% CI, 0.96–1.91) and deep vein thrombosis (DVT; HR, 1.52; 95% CI, 1.14–2.01). Similar results were found in analyses restricted to men, women, and elderly (aged greater than 75 years). Conclusion A weak HGS was associated with increased risk of VTE, and particularly unprovoked VTE and isolated DVT. Our findings suggest that weak muscle strength may be a risk factor for VTE

Physical capability, physical activity, and their association with femoral bone mineral density in adults aged 40 years and older: The Tromsø study 2015–2016

Summary: Since muscles can influence bone growth and vice versa, we examined if level of physical activity and physical capability tests can predict areal bone mineral density (aBMD). Both high activity level and good test performance were associated with higher aBMD, especially in women. Introduction: Muscle influences bone formation and vice versa. Tests of physical capability and level of physical activity reflect various muscle qualities. We assessed the associations between total hip aBMD and physical activity as well as a range of standardized physical capability tests in an adult general population. Methods: A total of 3 533 women and men aged 40-84 years, participating in the population-based cross-sectional Tromsø study in Norway in 2015-2016, were included. Linear regression was used to assess associations between aBMD and physical activity and the physical capability tests grip strength, Timed Up and Go (TUG), Short Physical Performance Battery (SPPB), and standing balance. Non-linear associations were examined in cubic spline models. Standardized regression coefficients were calculated to compare effect sizes across physical capability measures. Results: In fully adjusted models, higher physical activity was positively associated with total hip aBMD in both sexes compared to a sedentary lifestyle. All tests of physical capability were associated with aBMD in women, SPPB showing the strongest association although effect sizes were too small to indicate clinically significant differences (1 point increase corresponded to an aBMD increase of 0.009 g/cm2, CI = 0.005 to 0.012). In men, SPPB and its subtests were associated with aBMD with chair rises showing the strongest association (1 s increase in execution time corresponded to an aBMD decrease of 0.005 g/cm2, CI = 0.008 to 0.002). Conclusion: Physical activity was associated with aBMD, and tests of physical capability can account for some of the aBMD variations in adults aged 40 years and older, especially in women

Frailty phenotype and its association with all-cause mortality in community-dwelling Norwegian women and men aged 70 years and older: The Tromsø Study 2001-2016.

AIM: There is a lack of studies on the prevalence of frailty, and the association between frailty and mortality in a Norwegian general population. Findings regarding sex differences in the association between frailty and mortality have been inconsistent. The aim of the present study was to investigate the association between the frailty phenotype and all-cause mortality in men and women in a Norwegian cohort study. METHODS: We followed 712 participants (52% women) aged ≥70 years participating in the population-based Tromsø 5 Study in 2001-2002 for all-cause mortality up to 2016. The frailty status at baseline was defined by a modified version of Fried's frailty criteria. Cox regression models were used to analyze the association between frailty and mortality with adjustment for age, sex, disability, comorbidity, smoking status and years of education. RESULTS: In total, 3.8% (n = 27) of participants were frail (women 4.4%, men 3.2%) and 38.1% (n = 271) were pre-frail (women 45.8%, men 29.9%). During follow-up (mean 10.1 years), 501 (70%) participants died. We found an increased risk of mortality for frail older adults (multivariable-adjusted HR 4.16, 95% CI 2.40-7.22) compared with non-frail older adults. In sex-stratified analysis, the adjusted HR was 7.09 (95% CI 3.03-16.58) for frail men and 2.93 (95% CI 1.38-6.22) for frail women. Results for pre-frailty showed an overall weaker association with mortality. CONCLUSIONS: While frailty was more prevalent in women than in men, the findings suggest that the association between frailty and mortality is stronger in men than in women. Geriatr Gerontol Int 2018; 18: 1200-1205

Long-term trends of inequalities in mortality in 6 European countries

We aimed to assess whether trends in inequalities in mortality during the period 1970--2010 differed between Finland, Norway, England and Wales, France, Italy (Turin) and Hungary.Peer reviewe