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Objectives: Previous findings suggest a vascular foundation underlying apathy, but transdiagnostic and prospective evidence on vascular apathy is scarce. This study examines the association between vascular disease and the presence and development of apathy symptoms in the very old.Methods: Four cohorts of the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium were included in a two-staged, individual participant data meta-analysis using generalized linear mixed models, Vascular disease was defined as a history of any clinical atherosclerotic pathology (angina pectoris, myocardial infarction, intermittent claudication, transient ischemic attack, stroke or related surgeries) and was related to apathy symptoms as repeatedly measured by the Geriatric Depression Scale (GDS-3A >= 2) over a maximum of 5 years.Results: Of all 1868 participants (median age 85 years old), 53.9% had vascular disease and 44.3% experienced apathy symptoms. Participants with vascular disease had a 76% higher risk of apathy symptoms at baseline (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.32-2.35), irrespective of depressive symptoms and only partially explained by stroke. Conversely, there was no association of vascular disease with the occurrence of apathy symptoms longitudinally, both in those with apathy at baseline (OR 1.00, 95% CI 0.84-1.20) and without (OR 0.96, 95% CI 0.841.09).Conclusions: Vascular disease in the very old is associated with apathy symptoms cross-sectionally, but not proven longitudinally, independent of depressive symptoms. These findings query a vascular cause underlying apathy symptoms. However, the consistency of our cross-sectional findings in direction and magnitude across the TULIPS-consortium do emphasize international relevance of the interplay of vascular factors and apathy in advanced age, which meaning needs further unravelling.

Objectives: While randomized controlled trials have proven the benefits of blood pressure (BP) lowering in participating octogenarians, population-based observational studies suggest an association between low systolic blood pressure (SBP) and faster overall decline. This study investigates the effects of BP-lowering treatment, a history of cardiovascular diseases (CVD), and cognitive and physical fitness on the associations between SBP and health outcomes in the very old. Methods: Five cohorts from the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included in a two-step individual participant data meta-analysis (IPDMA). We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality and estimates of linear mixed models for change in cognitive and functional decline. Models were stratified by BP-lowering treatment, history of CVD, Mini-Mental State Examination scores, grip strength (GS) and body mass index (BMI). Results: Of all 2480 participants (59.9% females, median 85 years), median baseline SBP was 149 mmHg, 64.3% used BP-lowering drugs and 47.3% had a history of CVD. Overall, higher SBP was associated with lower all-cause mortality (pooled HR 0.91 [95% confidence interval 0.88-0.95] per 10 mmHg). Associations remained irrespective of BP-lowering treatment, history of CVD and BMI, but were absent in octogenarians with above-median MMSE and GS. In pooled cohorts, SBP was not associated with cognitive and functional decline. Conclusion: While in the very old with low cognitive or physical fitness a higher SBP was associated with a lower all-cause mortality, this association was not evident in fit octogenarians. SBP was not consistently associated with cognitive and functional decline.

BackgroundIn non-randomized studies (NRSs) where a continuous outcome variable (e.g., depressive symptoms) is assessed at baseline and follow-up, it is common to observe imbalance of the baseline values between the treatment/exposure group and control group. This may bias the study and consequently a meta-analysis (MA) estimate. These estimates may differ across statistical methods used to deal with this issue. Analysis of individual participant data (IPD) allows standardization of methods across studies. We aimed to identify methods used in published IPD-MAs of NRSs for continuous outcomes, and to compare different methods to account for baseline values of outcome variables in IPD-MA of NRSs using two empirical examples from the Thyroid Studies Collaboration (TSC).MethodsFor the first aim we systematically searched in MEDLINE, EMBASE, and Cochrane from inception to February 2021 to identify published IPD-MAs of NRSs that adjusted for baseline outcome measures in the analysis of continuous outcomes. For the second aim, we applied analysis of covariance (ANCOVA), change score, propensity score and the naïve approach (ignores the baseline outcome data) in IPD-MA from NRSs on the association between subclinical hyperthyroidism and depressive symptoms and renal function. We estimated the study and meta-analytic mean difference (MD) and relative standard error (SE). We used both fixed- and random-effects MA.ResultsTen of 18 (56%) of the included studies used the change score method, seven (39%) studies used ANCOVA and one the propensity score (5%). The study estimates were similar across the methods in studies in which groups were balanced at baseline with regard to outcome variables but differed in studies with baseline imbalance. In our empirical examples, ANCOVA and change score showed study results on the same direction, not the propensity score. In our applications, ANCOVA provided more precise estimates, both at study and meta-analytical level, in comparison to other methods. Heterogeneity was higher when change score was used as outcome, moderate for ANCOVA and null with the propensity score.ConclusionANCOVA provided the most precise estimates at both study and meta-analytic level and thus seems preferable in the meta-analysis of IPD from non-randomized studies. For the studies that were well-balanced between groups, change score, and ANCOVA performed similarly.

Background Daily functioning is known to decline after a hip fracture, but studies of self-reported functioning before the fracture suggest this decline begins before the fracture. Objective Determine whether change in functioning in the year before a hip fracture in very old (80+) differs from change in those without a hip fracture. Design Two-stage individual patient data meta-analysis including data from the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium. Setting Four population-based longitudinal cohorts from the Netherlands, New Zealand and the UK. Subjects Participants aged 80+ years. Methods Participants were followed for 5 years, during which (instrumental) activities of daily living [(I)ADL] scores and incident hip fractures were registered at regular intervals. Z-scores of the last (I)ADL score and the change in (I)ADL in the year before a hip fracture were compared to the scores of controls, adjusted for age and sex. Results Of the 2,357 participants at baseline, the 161 who sustained a hip fracture during follow-up had a worse (I)ADL score before the fracture (0.40 standard deviations, 95% CI 0.19 to 0.61, P = 0.0002) and a larger decline in (I)ADL in the year before fracture (−0.11 standard deviations, 95% CI −0.22 to 0.004, P = 0.06) compared to those who did not sustain a hip fracture. Conclusions In the very old a decline in daily functioning already starts before a hip fracture. Therefore, a hip fracture is a sign of ongoing decline and what full recovery is should be seen in light of the pre-fracture decline.

BACKGROUND Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). OBJECTIVE To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. METHODS We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. RESULTS Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. CONCLUSIONS Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

Objective To determine the physical and mental health of very old people (aged 80+) with anaemia. Methods Individual level meta-analysis from five cohorts of octogenarians (n = 2,392): LiLACS NZ Māori, LiLACS NZ non-Māori, Leiden 85-plus Study, Newcastle 85+ Study, and TOOTH. Mixed models of change in functional ability, cognitive function, depressive symptoms, and self-rated health over time were separately fitted for each cohort. We combined individual cohort estimates of differences according to the presence of anaemia at baseline, adjusting for age at entry, sex, and time elapsed. Combined estimates are presented as differences in standard deviation units (i.e. standardised mean differences–SMDs). Results The combined prevalence of anaemia was 30.2%. Throughout follow-up, participants with anaemia, on average, had: worse functional ability (SMD −0.42 of a standard deviation across cohorts; CI -0.59,-0.25); worse cognitive scores (SMD -0.27; CI -0.39,-0.15); worse depression scores (SMD -0.20; CI -0.31,-0.08); and lower ratings of their own health (SMD -0.36; CI -0.47,-0.25). Differential rates of change observed were: larger declines in functional ability for those with anaemia (SMD −0.12 over five years; CI -0.21,-0.03) and smaller mean difference in depression scores over time between those with and without anaemia (SMD 0.18 over five years; CI 0.05,0.30). Conclusion Anaemia in the very old is a common condition associated with worse functional ability, cognitive function, depressive symptoms, and self-rated health, and a more rapid decline in functional ability over time. The question remains as to whether anaemia itself contributes to worse outcomes or is simply a marker of chronic diseases and nutrient deficiencies.

TOPIC: Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. While the bidirectional association of VI and CIM has been hypothesized, findings have been equivocal. Hence, we conduct a systematic review and meta-analysis to examine the bidirectional relationship between VI and CIM. CLINICAL RELEVANCE: 60% risk of CIM has not been well-elucidated in the literature. A bidirectional relationship between CIM and VI may provide opportunities for developing public health strategies for early detection and management of risk factors for both VI and CIM in older people. METHODS: Pubmed, Embase and Cochrane Central registers were systematically searched for observational studies, published from inception until 6 April 2020, in adults aged ? 40 years reporting objectively measured VI, and CIM assessment using clinically validated cognitive screening tests or diagnostic evaluation. Meta-analyses on cross-sectional and longitudinal associations between VI and CIM outcomes (any CIM assessed using screening tests, and clinically diagnosed dementia) were examined. Random effect models were used to generate pooled odds ratios (OR), and 95% confidence interval (CI). Publication bias and heterogeneity were examined using Egger's test, meta-regression, and trim-and-fill methods. RESULTS: Forty studies were included (N=47,913,570). Meta-analyses confirmed that persons with VI were more likely to have CIM, with significantly higher odds [OR (95%CI)] of: (i) any CIM [cross-sectional: 2.38 (1.84-3.07); longitudinal: 1.66 (1.46-1.89)], and (ii) clinically diagnosed dementia [(cross-sectional: 2.43 (1.48-4.01); longitudinal: 2.09 (1.37-3.21)], compared to persons without VI. Significant heterogeneity was partially explained by differences in age, sex and follow-up duration. There was also some evidence that individuals with CIM, relative to cognitively intact persons, were more likely to have VI, with most papers (8/9, 89%) reporting significantly positive associations, however meta-analyses on this association could not be conducted due to insufficient data. CONCLUSIONS: Overall, our work suggests that VI is a risk factor of CIM while further work is needed to confirm the association of CIM as a risk factor for VI. Strategies for early detection and management of both visual and cognitive impairment in older people may minimize individual clinical and public health consequences.

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I 2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I 2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Background Multimorbidity and polypharmacy are very common in older adults in primary care. Ideally, general practitioners (GPs), should regularly review medication lists to identify inappropriate medication(s) and, where appropriate, deprescribe. However, it remains challenging to deprescribe given time constraints and few recommendations from guidelines. Further, patient related barriers and enablers to deprescribing have to be accounted for. The aim of this study was to identify barriers and enablers to deprescribing as reported by older adults with polypharmacy and multimorbidity. Methods We conducted a survey among participants aged ≥70 years, with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 chronic medications). We invited Swiss GPs, to recruit eligible patients who then completed a paper-based survey on demographics, medications and chronic conditions. We used the revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire and added twelve additional Likert scale questions and two open-ended questions to assess barriers and enablers towards deprescribing, which we coded and categorized into meaningful themes. Result Sixty four Swiss GPs consented to recruit 5–6 patients each and returned 300 participant responses. Participants were 79.1 years (SD 5.7), 47% female, 34% lived alone, and 86% managed their medications themselves. Sixty-seven percent of participants took 5–9 regular medicines and 24% took ≥10 medicines. The majority of participants (77%) were willing to deprescribe one or more of their medicines if their doctor said it was possible. There was no association with sex, age or the number of medicines and willingness to deprescribe. After adjustment for baseline characteristics, there was a strong positive association between willingness to deprescribe and saying that because they have a good relationship with their GP, they would feel that deprescribing was safe OR 11.3 (95% CI: 4.64–27.3) and agreeing that they would be willing to deprescribe if new studies showed an avoidable risk OR 8.0 (95% CI 3.79–16.9). From the open questions, the most mentioned barriers towards deprescribing were patients feeling well on their current medicines and being convinced that they need all their medicines. Conclusions Most older adults with polypharmacy are willing to deprescribe. GPs may be able to increase deprescribing by building trust with their patients and communicating evidence about the risks of medication use. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-020-01843-x.

BackgroundThe best management of hypertension in frail oldest-old (≥80 years of age) remains unclear and we still lack guidelines that provide specific recommendations. Our study aims to investigate guideline use in general practitioners (GPs) and to examine if guideline use relates to different decisions when managing hypertension in frail oldest-old.Design/settingCross-sectional study among currently active GPs from 29 countries using a case-vignettes survey.MethodsGPs participated in a survey with case-vignettes of frail oldest-olds varying in systolic blood pressure (SBP) levels and cardiovascular disease (CVD). GPs from 26 European countries and from Brazil, Israel and New Zealand were invited. We compared the percentage of GPs reporting using guidelines per country and further stratified on the most frequently mentioned guidelines. To adjust for patient characteristics (SBP, CVD and GPs' sex, years of experience, prevalence of oldest-old and location of their practice), we used a mixed-effects regression model accounting for clustering within countries.ResultsOverall, 2,543 GPs from 29 countries were included. 59.4% of them reported to use guidelines. Higher guideline use was found in female (p = 0.031) and less-experienced GPs (pConclusionMany GPs reported using guidelines to manage hypertension in frail oldest-old patients, however guideline users did not decide differently from non-users concerning hypertension treatment decisions. Instead of focusing on the fact if GPs use guidelines or not, we as a scientific community should put an emphasis on what guidelines suggest in frail and oldest-old patients.

Background: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely Presenting Older Patient (APOP) screening tool associates with clinical outcomes in this patient group.Methods: Patients aged >= 70 years who visited the Emergency Department (ED) and were acutely hospitalised for internal medicine were followed prospectively. The APOP screener assesses demographics, physical and cognitive function at ED presentation, and predicts 3-month mortality and functional decline in the older ED population. Patients with a predicted risk >= 45% were considered 'high risk'. Clinical outcome was hospital length of stay (LOS), and adverse outcomes were mortality and functional decline, 3 and 12 months after hospitalisation.Results: We included 319 patients, with a median age of 80 (IQR 74-85) years, of whom 94 (29.5%) were categorised as 'high risk' by the APOP screener. These patients had a longer hospital LOS compared to 'low risk' patients (5 (IQR 3-10) vs. 3 (IQR 1-7) days, respectively; p = 0.006). At 3 months, adverse outcomes were more frequent in 'high risk' patients compared to 'low risk' patients (59.6% vs. 34.7%, respectively; p < 0.001). At 12 months, adverse outcomes (67.0% vs. 46.2%, respectively; p = 0.001) and mortality (48.9% vs. 28.0%, respectively; p < 0.001) were greater in 'high risk' compared to 'low risk' patients.Conclusion: The APOP screener identifies acutely hospitalised internal medicine patients at high risk for poor short and long-term outcomes. Early risk stratification at admission could aid in individualised treatment decisions to optimise outcomes for older patients.

IntroductionMultimorbidity and polypharmacy are current challenges when caring for the older population. Both have led to an increase of potentially inappropriate medication (PIM), illustrating the need to assess patients' attitudes towards deprescribing. We aimed to assess the prevalence of PIM use and whether this was associated with patient factors and willingness to deprescribe.MethodWe analysed data from the LESS Study, a cross-sectional study on self-reported medication and on barriers and enablers towards the willingness to deprescribe (rPATD questionnaire). The survey was conducted among multimorbid (≥3 chronic conditions) participants ≥70 years with polypharmacy (≥5 long-term medications). A subset of the Beers 2019 criteria was applied for the assessment of medication appropriateness.ResultsData from 300 patients were analysed. The mean age was 79.1 years (SD 5.7). 53% had at least one PIM (men: 47.8%%, women: 60.4%%; p = 0.007). A higher number of medications was associated with PIM use (p = 0.002). We found high willingness to deprescribe in both participants with and without PIM. Willingness to deprescribe was not associated with PIM use (p = 0.25), nor number of PIMs (p = 0.81).ConclusionThe willingness of older adults with polypharmacy towards deprescribing was not associated with PIM use in this study. These results suggest that patients may not be aware if they are taking PIMs. This implies the need for raising patients' awareness about PIMs through education, especially in females, in order to implement deprescribing in daily practice.

Importance Subclinical hypothyroidism has been associated with heart failure, but no conclusive clinical trial assessed whether treating subclinical hypothyroidism with levothyroxine has an impact on cardiac function. Objective To assess the impact of levothyroxine treatment on cardiac function in subclinical hypothyroidism. Design This is a randomized, double-blind placebo-controlled, multicenter Swiss substudy within the TRUST trial. Participants Participants aged ≥65 years with subclinical hypothyroidism. Intervention Levothyroxine to achieve TSH normalization, or placebo including mock titrations. Main outcome measures Primary outcomes, assessed by echocardiography at the end of the trial were the left ventricular ejection fraction (LVEF, normal defined as >50%) for systolic function and the ratio between mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (e' (E/e' ratio) for diastolic function. Secondary outcomes included transmitral E and A waves, e' lateral/septal, left atrial (LA) volume index and systolic pulmonary artery pressure. Results Of 217 randomized Swiss participants of the TRUST trial, 185 (mean age 74.1 years, 47% women, mean TSH at baseline 6.35 ± SD 1.95 mIU/L) underwent echocardiography. After a median treatment duration of 18.4 months, the mean TSH among participants randomized to levothyroxine (n=95) decreased to 3.55 mIU/L, whereas it remained elevated in the placebo group (n=89; 5.29 mIU/L). The mean LVEF was similar in both arms (adjusted between-group difference 0.4%, 95% CI −1.8% to 2.5%, P=0.72) and no significant differences were found for the E/e' ratio (adjusted between-group difference 0.4, 95% CI −0.7 to 1.4, P=0.47). In intention-to-treat and per-protocol analyses, no clinically significant differences were found for secondary diastolic function parameters: e' lateral 8 vs. 8 cm/s, P=0.54; e' septal 6 vs. 6 cm/s, P=0.75; LA volume index 34 vs. 33 ml/m2, P=0.57; E/A ratio 0.8 vs. 0.8, P=0.94; E deceleration time 225 vs. 216 ms, P=0.27, except for systolic pulmonary artery pressure (37 mm Hg in the levothyoxine group vs. 33 mm Hg in the placebo group, P=0.02 intention-to-treat and P=0.06 per protocol) Conclusion Treatment of subclinical hypothyroidism with levothyroxine was not associated with benefits regarding systolic and diastolic heart function in older adults with subclinical hypothyroidism.