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AIMS AND OBJECTIVES This study evaluated the impact of a consultant-led Acute Care at Home service in comparison with conventional hospital admission to a care of elderly ward. BACKGROUND Globally, there has been an increased demand for healthcare services caused by population growth and a rise in chronic conditions and an ageing population. Acute Care at Home services offer acute, hospital-level care in a person's own home. Five services have been commissioned across Northern Ireland since 2014 with limited research investigating their feasibility and effectiveness. DESIGN Quantitative design, using service evaluation methodology. METHODS A 1-year retrospective chart review was undertaken exploring admission demographics and post-discharge clinical outcomes of patients admitted to a Northern Ireland, Care of the Elderly ward (n = 191) and a consultant-led Acute Care at Home Service (n = 314) between April 2018-March 2019. Data were analysed using descriptive and inferential data analysis methods including frequencies, independent t tests and chi-square analysis. Outcome measurements included length of stay, 30-day, 3- and 6-month readmission and mortality rates, functional ability and residence on discharge. STROBE checklist was used in reporting this study. RESULTS Acute Care at Home services are associated with higher readmission and mortality rates at 30 days, 3 and 6 months. Fewer patients die while under Acute Care at Home care. Patients admitted to the Acute Care at Home services experience a reduced length of stay and decreased escalation in domiciliary care packages and are less likely to require subacute rehabilitation on discharge. There is no difference in gender, age and early warnings score between the two cohorts. CONCLUSION The Acute Care at Home service is a viable alternative to hospital for older patients. It prevents functional decline and the need for domiciliary care or nursing home placement. It is likely that the Acute Care at Home service has higher mortality and readmissions rates due to treating a higher proportion of dependent, frail older adults. RELEVANCE TO CLINICAL PRACTICE Acute Care at Home services continue to evolve worldwide. This service evaluation has confirmed that Acute Care at Home services are safe and cost-effective alternatives to traditional older people hospital services. Such services offer patient choice, reduce length of stay and costs and prevent functional decline of older adults. This study accentuates the need to expand Acute Care at Home provision and capacity throughout Northern Ireland.

Background Dementia is caused by a variety of neurodegenerative diseases and is associated with a decline in memory and other cognitive abilities, while inflicting an enormous socioeconomic burden. The complexity of dementia and its associated comorbidities presents immense challenges for dementia research and care, particularly in clinical decision-making. Main body Despite the lack of disease-modifying therapies, there is an increasing and urgent need to make timely and accurate clinical decisions in dementia diagnosis and prognosis to allow appropriate care and treatment. However, the dementia care pathway is currently suboptimal. We propose that through computational approaches, understanding of dementia aetiology could be improved, and dementia assessments could be more standardised, objective and efficient. In particular, we suggest that these will involve appropriate data infrastructure, the use of data-driven computational neurology approaches and the development of practical clinical decision support systems. We also discuss the technical, structural, economic, political and policy-making challenges that accompany such implementations. Conclusion The data-driven era for dementia research has arrived with the potential to transform the healthcare system, creating a more efficient, transparent and personalised service for dementia.

BackgroundClinical Dementia Rating Sum of Boxes (CDRSOB) scale is known to be highly indicative of cognitive-functional status, but it is unclear whether it is consistent with clinician diagnosis in evaluating drug class associations with risk of progression to mild cognitive impairment (MCI) and dementia. MethodsWe employed multivariate logistic regression on longitudinal NACC data, to identify drug classes associated with disease progression risk, using clinician diagnosis and CDRSOB as the outcome. ResultsNon-steroidal anti-inflammatory drugs, anxiolytics, antidiabetics, and Parkinsons medications were significantly associated with decreased progression to mild cognitive impairment (MCI)/dementia, and antihypertensives and Alzheimers medications significantly associated with increased progression risk. Associations were however dependant on the diagnostic measure used, e.g., antihypertensives were associated with increased Healthy-to-Dementia risk using clinical diagnosis as the outcome (OR:2.05, FDR p

Purpose Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed to adolescents for moderate pain related to minor trauma or dental, surgical, or medical procedures. Pharmacokinetic and pharmacodynamic differences between these opioids could affect their relative safety. We aimed to compare occurrence of opioid-related adverse events in adolescents without cancer or other severe conditions taking hydrocodone, codeine, oxycodone, and tramadol. Methods Retrospective cohort study of 201 940 Tennessee Medicaid enrollees 12 to 17 years of age without cancer, other severe conditions, or evidence of substance abuse with 529 731 filled prescriptions for study opioids. Adverse events were defined as an emergency department visit, hospital admission, or death related to opioid use, confirmed by medical record review. Serious events had opioid-related escalation of care, hospitalization, or death. Propensity-score adjusted hazard ratios (HRs) were calculated with hydrocodone as the reference category. Results The incidence of opioid-related adverse events per 10 000 person-years of opioid exposure was 97.5 for hydrocodone (127 events/13 026 person-years), 91.2 for codeine (58/6,359), 229.7 for oxycodone (43/1,872), and 317.7 for tramadol (47/1479). The HRs for tramadol in comparison with hydrocodone for all and serious events were 2.98 (2.03-4.39) and 2.94 (1.81-4.75), respectively. Increased risk for tramadol was consistently present when the adverse events were restricted to those with neurologic-respiratory depression/other symptoms of possible overdose. Conclusion In adolescents without cancer or other severe conditions prescribed short-acting opioids, the incidence of both all opioid-related adverse events and more serious events with opioid-related escalation of care, hospitalization, or death was consistently greater for tramadol than for hydrocodone.

BACKGROUND: This is an update of a Cochrane Review first published in 2006 (McGuinness 2006), and previously updated in 2009 (McGuinness 2009). Hypertension is a risk factor for dementia. Observational studies suggest antihypertensive treatment is associated with lower incidences of cognitive impairment and dementia. There is already clear evidence to support the treatment of hypertension after stroke.OBJECTIVES: To assess whether pharmacological treatment of hypertension can prevent cognitive impairment or dementia in people who have no history of cerebrovascular disease.SEARCH METHODS: We searched the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, CENTRAL, MEDLINE, Embase, three other databases, as well as many trials registries and grey literature sources, most recently on 7 July 2020.SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which pharmacological interventions to treat hypertension were given for at least 12 months. We excluded trials of pharmacological interventions to lower blood pressure in non-hypertensive participants. We also excluded trials conducted solely in people with stroke.DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected information regarding incidence of dementia, cognitive decline, change in blood pressure, adverse effects and quality of life. We assessed the certainty of evidence using GRADE.MAIN RESULTS: We included 12 studies, totaling 30,412 participants, in this review. Eight studies compared active treatment with placebo. Of the four non-placebo-controlled studies, two compared intensive versus standard blood pressure reduction. The two final included studies compared different classes of antihypertensive drug. Study durations varied from one to five years. The combined result of four placebo-controlled trials that reported incident dementia indicated no evidence of a difference in the risk of dementia between the antihypertensive treatment group and the placebo group (236/7767 versus 259/7660, odds ratio (OR) 0.89, 95% confidence interval (CI) 0.72 to 1.09; very low certainty evidence, downgraded due to study limitations and indirectness). The combined results from five placebo-controlled trials that reported change in Mini-Mental State Examination (MMSE) may indicate a modest benefit from antihypertensive treatment (mean difference (MD) 0.20, 95% CI 0.10 to 0.29; very low certainty evidence, downgraded due to study limitations, indirectness and imprecision). The certainty of evidence for both cognitive outcomes was downgraded on the basis of study limitations and indirectness. Study durations were too short, overall, to expect a significant difference in dementia rates between groups. Dementia and cognitive decline were secondary outcomes for most studies. Additional sources of bias include: the use of antihypertensive medication by the placebo group in the placebo-controlled trials; failure to reach recruitment targets; and early termination of studies on safety grounds. Meta-analysis of the placebo-controlled trials reporting results found a mean change in systolic blood pressure of -9.25 mmHg (95% CI -9.73, -8.78) between treatment (n = 8973) and placebo (n = 8820) groups, and a mean change in diastolic blood pressure of -2.47 mmHg (95% CI -2.70, -2.24) between treatment (n = 7700) and placebo (n = 7509) groups (both low certainty evidence downgraded on the basis of study limitations and inconsistency). Three trials - SHEP 1991, LOMIR MCT IL 1996 and MRC 1996 - reported more withdrawals due to adverse events in active treatment groups than placebo groups. Participants on active treatment in Syst Eur 1998 were less likely to discontinue treatment due to side effects, and participants on active treatment in HYVET 2008 reported fewer 'serious adverse events' than in the placebo group. There was no evidence of a difference in withdrawals rates between groups in SCOPE 2003, and results were unclear for Perez Stable 2000 and Zhang 2018. Heterogeneity precluded meta-analysis. Five of the placebo-controlled trials provided quality of life (QOL) data. Heterogeneity again precluded meta-analysis. SHEP 1991, Syst Eur 1998 and HYVET 2008 reported no evidence of a difference in QOL measures between active treatment and placebo groups over time. The SCOPE 2003 sub-study (Degl'Innocenti 2004) showed a smaller drop in QOL measures in the active treatment compared to the placebo group. LOMIR MCT IL 1996 reported an improvement in a QOL measure at twelve months in one active treatment group and deterioration in another.AUTHORS' CONCLUSIONS: High certainty randomised controlled trial evidence regarding the effect of hypertension treatment on dementia and cognitive decline does not yet exist. The studies included in this review provide low certainty evidence (downgraded primarily due to study limitations and indirectness) that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, leads to less cognitive decline compared to controls. This difference is below the level considered clinically significant. The studies included in this review also provide very low certainty evidence that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, prevents dementia.

The increasing prevalence of dementia in older adults warrants attention to the identification of practices that can delay or reduce likelihood of progression to early forms of cognitive impairment, in particular, to mild cognitive impairment (MCI) which is often considered a transitional stage between healthy aging and dementia. In this study, we investigated the effect of hearing impairment and hearing aid usage on cognitive decline and progression to MCI in cognitively healthy individuals. We used data from a large referral-based cohort obtained from the National Alzheimer’s Coordinating Center. The baseline sample included 5721 cognitively normal subjects aged ≥ 40. We found that hearing impairment was associated with increased risk of progression to MCI (hazard ratio [HR] = 1.40, 95%CI, 1.16-1.68, false discovery rate [FDR] P < 0.001) and an accelerated rate of cognitive decline (P < 0.001). Among hearing-impaired participants, hearing aid users were less likely to develop MCI (HR, 0.33; 95% CI, 0.23-0.47; FDR P < 0.001) and experienced slower cognitive decline (P = 0.004) when compared to those not using hearing aids. We found no statistically significant differences in risk of conversion to MCI between individuals with normal hearing and hearing-impaired adults using hearing aids (HR, 1.23; 95% CI, 0.99-1.50; FDR P = 0.08). Our findings highlight the need for a randomized clinical trial that will allow us to investigate whether there is a causal relationship between hearing loss, hearing aid use, and conversion to MCI. Such knowledge could provide new and novel insights into prevention of cognitive impairment and dementia.

INTRODUCTIONHearing aid usage has been linked to improvements in cognition, communication, and socialization, but the extent to which it can affect the incidence and progression of dementia is unknown. Such research is vital given the high prevalence of dementia and hearing impairment in older adults, and the fact that both conditions often coexist. In this study, we examined for the first time the effect of the use of hearing aids on the conversion from mild cognitive impairment (MCI) to dementia and progression of dementia.METHODSWe used a large referral-based cohort of 2114 hearing-impaired patients obtained from the National Alzheimer’s Coordinating Center. Survival analyses using multivariable Cox proportional hazards regression model and weighted Cox regression model with censored data were performed to assess the effect of hearing aid use on the risk of conversion from MCI to dementia and risk of death in hearing-impaired participants. Disease progression was assessed with CDR® Dementia Staging Instrument Sum of Boxes (CDRSB) scores. Three types of sensitivity analyses were performed to validate the robustness of the results.RESULTSMCI participants that used hearing aids were at significantly lower risk of developing all-cause dementia compared to those not using hearing aids (hazard ratio [HR] 0.73, 95%CI, 0.61-0.89; false discovery rate [FDR] P=0.004). The mean annual rate of change (standard deviation) in CDRSB scores for hearing aid users with MCI was 1.3 (1.45) points and significantly lower than for individuals not wearing hearing aids with a 1.7 (1.95) point increase in CDRSB per year (P=0.02). No association between hearing aid use and risk of death was observed. Our findings were robust subject to sensitivity analyses.DISCUSSIONAmong hearing-impaired adults, hearing aid use was independently associated with reduced dementia risk. The causality between hearing aid use and incident dementia should be further tested.HighlightsHigh prevalence of dementia and hearing impairment in older adultsHearing aid (HA) use associated with a lower risk of incident dementiaSlower cognitive decline in users than non-users of HA with mild cognitive impairmentThe relationship between hearing impairment and dementia should be further tested

The symptoms of (PD) often begins on one side of the body before separating bilaterally. Early symptoms of PD are rest tremors, bradykinesia and rigidity. Common signs are a decrease in arm swing, shuffling foot movement and slowness arising from a chair. Rigidity of muscles commonly affects a patient limbs, neck and shoulder PD is currently diagnosed after the neuro degenerative process has started. To optimize and improve PD quality of care, it should be diagnosed early in its onset once symptoms are not yet evident. The current gold standard for patient assessment of PD is the completion of symptom diaries. These diaries are subjective and usually do not accurately reflect what is taking place throughout the day. It is exceedingly difficult for an untrained observer such as family members to provide accurate description of movement characteristic in PD. An alternative way to exercise the abnormal movement in PD is to use a wearable technology system which could aid early detection of the disease and help clinicians manage medication when symptoms fluctuate throughout the day. This paper will evaluate the effectiveness of a wearable multi-sensor kinematic system capable of detecting the tell-tale signs of PD when performing tailored exercise routines. Each exercise routine will examine movement for potential PD symptoms and report finding for deeper clinician analysis.

Sporadic early-onset Alzheimer’s disease (sEOAD) exhibits the symptoms of late-onset Alzheimer’s disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer’s disease (AD) identifies APOE ε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases was genotyped on the NeuroX array, and PRSs were generated using PRSice. The target data set consisted of 408 sEOAD cases and 436 controls. The base data set was collated by the International Genomics of Alzheimer’s Project consortium, with association data from 17,008 late-onset Alzheimer’s disease cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRSs were generated using all common single nucleotide polymorphisms between the base and target data set, PRS were also generated using only single nucleotide polymorphisms within a 500 kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap among the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy.

Editor – Akintade and Pierres provide a useful review of the evaluation of cognitive impairment in their Acute Medical Care (AMC) report in July’s Clinical Medicine .[1][1] However, the patient described in their report does not have dementia with Lewy bodies (DLB). Akintade and Pierres cite

Alcohol is a commonly abused substance, and it is important that healthcare facilities properly manage alcohol withdrawal. Studies have found that the most efficient way to manage alcohol withdrawal is to use a symptom-triggered approach and only administer medications if symptoms surpass a specific threshold determined by a clinician administered rating scale. Alternatively, a standard fixed-dose medication regimen can be utilized. This study assessed if a new symptom-triggered protocol, utilizing the Clinical Institute Withdrawal for Alcohol, Revised (CIWA-Ar) scale for the assessment of symptoms, resulted in the anticipated patient outcomes of decreased length of hospital stay, less benzodiazepine administered per patient, and a shorter administration time from first dose of benzodiazepine given to last dose, when compared to the previous standard of care. A retrospective chart review was performed for 70 patients who had been treated for alcohol withdrawal. Patients who were treated with the symptom-triggered protocol had a decreased length of hospital stay when compared to the previous standard of care (−2.62 days, p = 0.0054). Both secondary efficacy outcomes were also statistically significant in favor of the symptom-triggered group. This retrospective chart review adds to the body of evidence supporting the use of symptom-triggered protocols as opposed to fixed-dose protocols in the management of alcohol withdrawal.

Aim: Substantial evidence links atherosclerosis and Alzheimer’s disease (AD). Apolipoproteins, such as apolipoprotein E, have a causal relationship with both diseases. The rs11136000 SNP within the CLU gene, which encodes clusterin (apolipoprotein J), is also associated with increased AD risk. The aim of this study was to investigate the relationship between plasma clusterin and the rs11136000 genotype in mild cognitive impairment (MCI) and AD. Methods: Plasma and DNA samples were collected from control, MCI and AD subjects (n=142, 111, 154, respectively). Plasma clusterin was determined by ELISA and DNA samples were genotyped for rs11136000 by TaqMan assay. Results: Plasma clusterin levels were higher in MCI and AD subjects vs. controls (222.3±61.3 and 193.6±58.2 vs. 178.6±52.3 g/ml, respectively; p

Introduction: We present the results of a pilot study to test the feasibility of a brachytherapy dosimetry audit. Methods: The feasibility study was conducted at seven sites from four Australian states in both public and private centres. A purpose-built cylindrical water phantom was imaged using the local imaging protocol and a treatment plan was generated to deliver 1 Gy to the central (1 of 3) thermoluminescent dosimeter (TLD) from six dwell positions. Results: All centres completed the audit, consisting of three consecutive irradiations, within a 2-h time period, with the exception of one centre that uses a pulsed dose rate brachytherapy unit. All TLD results were within 4.5% of the predicted value, with the exception of one subset where the dwell position step size was incorrectly applied. Conclusions: While the limited data collected in the study demonstrated considerable heterogeneity in clinical practice, the study proved a brachytherapy dosimetry audit to be feasible. Future studies should include verification of source strength using a Standard Dosimetry Laboratory calibrated chamber, a phantom that more closely mimics the clinical situation, a more comprehensive review of safety and quality assurance (QA) procedures including source dwell time and position accuracy, and a review of patient treatment QA procedures such as applicator position verification.

Dementia currently exacts a substantial economic burden on societies, health and social care systems and carers in addition to the devastating personal and emotional cost to patients and families (1,2). This burden is predicted to increase substantially in the coming decades and is the major public health issue of this century (1). Currently available therapies are symptomatic only (3), with little or no prospect of disease-modifying treatments entering routine clinical use in the short to medium term. Strategies to prevent or delay the onset of dementia or retard its' progression are, therefore, urgently required and will be of extreme importance to individuals and societies. Currently available medications that could achieve these goals would have many advantages ― potential for immediate use; established safety profile; familiarity to clinicians; relatively low cost giving favourable cost-effectiveness breakdown.

Bernadette McGuinness, David Wilson, Stephen Todd and Peter Passmore provide an introduction to the use of acetylcholinesterase inhibitors in Alzheimer's disease. They look at the potential benefits and limitations of the drugs, highlight the importance of regular review, and provide guidance about maximising the benefits of treatment, and deciding when to discontinue or switch medications.

Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the Abeta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.

β-Secretase activity is the rate-limiting step in Aβ peptide production from amyloid precursor protein. Aβ is a major component of Alzheimer's disease (AD) cortical amyloid plaques. β-Secretase activity is elevated in post mortem brain tissue in AD. The current study investigated whether β-secretase activity was also elevated in peripheral blood platelets. We developed a novel fluorimetric β-secretase activity assay to investigate platelets isolated from individuals with AD ( n = 86), and age-matched controls ( n = 115). Platelet membrane β-secretase activity (expressed as initial rate) varied over fourfold between individuals, raising important questions about in vivo regulation of this proteolytic activity. Nonetheless, we identified a significant 17% increase in platelet membrane β-secretase activity in individuals with AD compared to controls ( p = 0.0003, unpaired t -test). Platelet membrane β-secretase activity did not correlate with mini-mental state examination (MMSE) score in the AD group (mean MMSE = 17.7, range 1–23), indicating that the increase did not occur as a secondary result of the disease process, and may even have preceded symptom onset.

Background/Aims: We have recently reported that platelet activity of the rate-limiting enzyme for β-amyloid peptide production is elevated in established Alzheimer’s disease. Laboratory investigation of the very early stages of dementia provides an opportunity to investigate pathological mechanisms before advanced disease hinders interpretation. Mild cognitive impairment (MCI) exists prior to obvious dementia, and is associated with increased risk of conversion to overt disease. Methods: We developed and used a fluorimetric assay to quantify platelet membrane β-secretase activity in 52 patients with MCI and 75 controls. Results: Platelet membrane β-secretase activity was 24% higher in individuals with MCI compared to controls (p = 0.001, unpaired t test with Welch correction). Conclusion: Elevated platelet β-secretase activity in subjects with MCI is an area for further study in relation to the etiology and diagnosis of MCI.

Background: Reporting of cause of death in patients with Alzheimer’s disease (AD) has changed over the past few decades but concerns persist over the accuracy of death certificate completion in this setting. Objectives: To examine the causes of death in AD and examine how this compares with those affecting the normal population. Methods: Death certificates were obtained for 85 AD patients and 52 control subjects from a cohort of 396 participants. Underlying causes of death and other conditions mentioned on the death certificates of the AD patients were analysed and compared with the Northern Ireland population age-and-sex adjusted mortality rates and subsequently to the death certificates of control subjects. Results : AD and pneumonia were causes of significant excess mortality and the most common underlying causes of death in the AD patient group (23.53 and 17.65%, respectively). When compared with the control subjects, AD and gastrointestinal diseases were found to be more prevalent. AD was recorded on 63.5% of death certificates of AD subjects who died during follow-up. Conclusion: The cause of death documented for AD patients may be affected by the physician’s knowledge of the patient or reflects the approach to management of patients with end-stage dementia.

BACKGROUND: This is an update of a Cochrane Review first published in 2006 (McGuinness 2006), and previously updated in 2009 (McGuinness 2009). Hypertension is a risk factor for dementia. Observational studies suggest antihypertensive treatment is associated with lower incidences of cognitive impairment and dementia. There is already clear evidence to support the treatment of hypertension after stroke. OBJECTIVES: To assess whether pharmacological treatment of hypertension can prevent cognitive impairment or dementia in people who have no history of cerebrovascular disease. SEARCH METHODS: We searched the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, CENTRAL, MEDLINE, Embase, three other databases, as well as many trials registries and grey literature sources, most recently on 7 July 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which pharmacological interventions to treat hypertension were given for at least 12 months. We excluded trials of pharmacological interventions to lower blood pressure in non‐hypertensive participants. We also excluded trials conducted solely in people with stroke. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected information regarding incidence of dementia, cognitive decline, change in blood pressure, adverse effects and quality of life. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 studies, totaling 30,412 participants, in this review. Eight studies compared active treatment with placebo. Of the four non‐placebo‐controlled studies, two compared intensive versus standard blood pressure reduction. The two final included studies compared different classes of antihypertensive drug. Study durations varied from one to five years. The combined result of four placebo‐controlled trials that reported incident dementia indicated no evidence of a difference in the risk of dementia between the antihypertensive treatment group and the placebo group (236/7767 versus 259/7660, odds ratio (OR) 0.89, 95% confidence interval (CI) 0.72 to 1.09; very low certainty evidence, downgraded due to study limitations and indirectness). The combined results from five placebo‐controlled trials that reported change in Mini‐Mental State Examination (MMSE) may indicate a modest benefit from antihypertensive treatment (mean difference (MD) 0.20, 95% CI 0.10 to 0.29; very low certainty evidence, downgraded due to study limitations, indirectness and imprecision). The certainty of evidence for both cognitive outcomes was downgraded on the basis of study limitations and indirectness. Study durations were too short, overall, to expect a significant difference in dementia rates between groups. Dementia and cognitive decline were secondary outcomes for most studies. Additional sources of bias include: the use of antihypertensive medication by the placebo group in the placebo‐controlled trials; failure to reach recruitment targets; and early termination of studies on safety grounds. Meta‐analysis of the placebo‐controlled trials reporting results found a mean change in systolic blood pressure of ‐9.25 mmHg (95% CI ‐9.73, ‐8.78) between treatment (n = 8973) and placebo (n = 8820) groups, and a mean change in diastolic blood pressure of ‐2.47 mmHg (95% CI ‐2.70, ‐2.24) between treatment (n = 7700) and placebo (n = 7509) groups (both low certainty evidence downgraded on the basis of study limitations and inconsistency). Three trials ‐ SHEP 1991, LOMIR MCT IL 1996 and MRC 1996 ‐ reported more withdrawals due to adverse events in active treatment groups than placebo groups. Participants on active treatment in Syst Eur 1998 were less likely to discontinue treatment due to side effects, and participants on active treatment in HYVET 2008 reported fewer 'serious adverse events' than in the placebo group. There was no evidence of a difference in withdrawals rates between groups in SCOPE 2003, and results were unclear for Perez Stable 2000 and Zhang 2018. Heterogeneity precluded meta‐analysis. Five of the placebo‐controlled trials provided quality of life (QOL) data. Heterogeneity again precluded meta‐analysis. SHEP 1991, Syst Eur 1998 and HYVET 2008 reported no evidence of a difference in QOL measures between active treatment and placebo groups over time. The SCOPE 2003 sub‐study (Degl'Innocenti 2004) showed a smaller drop in QOL measures in the active treatment compared to the placebo group. LOMIR MCT IL 1996 reported an improvement in a QOL measure at twelve months in one active treatment group and deterioration in another. AUTHORS' CONCLUSIONS: High certainty randomised controlled trial evidence regarding the effect of hypertension treatment on dementia and cognitive decline does not yet exist. The studies included in this review provide low certainty evidence (downgraded primarily due to study limitations and indirectness) that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, leads to less cognitive decline compared to controls. This difference is below the level considered clinically significant. The studies included in this review also provide very low certainty evidence that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, prevents dementia.

Introduction Although there is evidence for distinct behavioural sub-phenotypes in Alzheimer's disease (AD), their inter-relationships and the effect of clinical variables on their expression have been little investigated. Methods We have analysed a sample of 1850 probable AD patients from the UK and Greece with 10 item Neuropsychiatric Inventory (NPI) data. We applied aMultipleIndicatorsMultipleCauses (MIMIC) approach to investigate the effect of MMSE, disease duration, gender, age and age of onset on the structure of a four-factor model consisting of “psychosis”, “moods”, “agitation” and “behavioural dyscontrol”. Results Specific clinical variables predicted the expression of individual factors. When the inter-relationship of factors is modelled, some previously significant associations are lost. For example, lower MMSE scores predict psychosis, agitation and behavioural dyscontrol factors, but psychosis and mood predict the agitation factor. Taking these associations into account MMSE scores did not predict agitation. Conclusions The complexity of the inter-relations between symptoms, factors and clinical variables is efficiently captured by this MIMICmodel.

Hypertension and cognitive impairment are prevalent in older people. Hypertension is a direct risk factor for vascular dementia, and recent studies suggest hypertension also impacts on the prevalence of Alzheimer’s disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. To assess the effects of blood pressure (BP) lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. Trials were identified through a search of the Cochrane Dementia and Cognitive Impairment Group’s Specialised Register which contains records from CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL. Relevant journals were searched, drug companies, colleagues and researchers were contacted, and reference lists of all trials identified were screened. Randomised, double blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower BP were given for at least 6 months. Two independent reviewers assessed trial …

Although epidemiological studies suggest that type 2 diabetes mellitus (T2DM) increases the risk of late-onset Alzheimer's disease (LOAD), the biological basis of this relationship is not well understood. The aim of this study was to examine the genetic comorbidity between the 2 disorders and to investigate whether genetic liability to T2DM, estimated by a genotype risk scores based on T2DM associated loci, is associated with increased risk of LOAD. This study was performed in 2 stages. In stage 1, we combined genotypes for the top 15 T2DM-associated polymorphisms drawn from approximately 3000 individuals (1349 cases and 1351 control subjects) with extracted and/or imputed data from 6 genome-wide studies (>10,000 individuals; 4507 cases, 2183 controls, 4989 population controls) to form a genotype risk score and examined if this was associated with increased LOAD risk in a combined meta-analysis. In stage 2, we investigated the association of LOAD with an expanded T2DM score made of 45 well-established variants drawn from the 6 genome-wide studies. Results were combined in a meta-analysis. Both stage 1 and stage 2 T2DM risk scores were not associated with LOAD risk (odds ratio = 0.988; 95% confidence interval, 0.972-1.004; p = 0.144 and odds ratio = 0.993; 95% confidence interval, 0.983-1.003; p = 0.149 per allele, respectively). Contrary to expectation, genotype risk scores based on established T2DM candidates were not associated with increased risk of LOAD. The observed epidemiological associations between T2DM and LOAD could therefore be a consequence of secondary disease processes, pleiotropic mechanisms, and/or common environmental risk factors. Future work should focus on well-characterized longitudinal cohorts with extensive phenotypic and genetic data relevant to both LOAD and T2DM.

2099 Background: Although meningioma is the most common tumor in the central nervous system (CNS), the incidence, epidemiology, and clinical outcomes have historically been poorly defined. Our analysis follows the implementation of Public Law 107–260, the Benign Brain Tumor Cancer Registries Act mandating collection of non-malignant meningiomas. Methods: Surveillance Epidemiology End Results Program (SEER) 18 registries research data on cases diagnosed during 2004-2009 with meningioma (ICD-O-3 histology codes 9530-9534 & 9537-9539) in brain or CNS primary site (C70.0-72.9, 75.1-75.3 ) were analyzed. Population-based statistics were generated using SEER*Stat 8.0.1 software. Results: A total of 35,302 cases (34,718 non-malignant; 584 malignant) were available providing a rate of 7.18/100,000, with meningioma, NOS (9530/0) the most common histology. Rates increased with age (0.13/100,000, 0-19 years; 37.78/100,000, 75+ years). The annual percentage change in incidence rates showed a statistically significant increase of 2.57% over 2004-2009. Significant increases were also observed for males, females, whites, blacks, non-Hispanics, and older age groups. The gender ratio M:F was 0.35 in the 0-49 age group and 0.48 in the 50+ age. Primary site location included cerebral meninges (83%) with almost 5% in the spinal meninges. 51% of cases were diagnosed pathologically versus imaging. However, diagnosis among 85% of spinal cases was surgically based. Older age and females were less likely to have a surgical diagnosis. 3.4% received radiation therapy (RT) with 97% receiving RT following surgery. For grade III or malignant cases, 22% received RT, and in grade 1 and 2 nearly 97% of cases did not receive RT, with older age groups less likely to receive RT. Overall survival was high, except for grade 3 or malignant cases where 5 year relative survival was 61.7%. Conclusions: Our analysis following Public Law 107–260 demonstrates an increasing incidence of meningiomas and provides new information, including a decrease in the gender difference with age. Clinical diagnosis is common and higher in women and older adults. Use of RT is low, even in malignant meningiomas, and employed following surgery. These observations were similar for white and black cases.