A qualitative study to inform adaptations to a brain health intervention for older adults with type 2 diabetes living in rural regions of Ireland.

AIMS: Type 2 diabetes is a risk factor for late-life dementia, but dementia prevention strategies have yet to be comprehensively evaluated in people with diabetes. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated cognitive benefits of a 2-year multidomain lifestyle intervention. However, given the intensive nature of FINGER, there is uncertainty about whether it can be implemented in other high-risk populations. Our aim was to explore attitudes towards dementia risk, and barriers to an intervention based on the FINGER model in older adults with type 2 diabetes living in rural areas of Ireland. METHODS: Focus groups were conducted with 21 adults (11 men and 10 women) aged 60+ years with type 2 diabetes living in border regions of north and south Ireland. Data were analysed using thematic analysis. RESULTS: There was limited understanding of diabetes as a risk factor for late-life dementia. The main barriers to engagement with the multidomain intervention were eating foods that were not compatible with cultural norms, time and travel constraints, and perceived lack of self-efficacy and self-motivation for adopting the desired diet, exercise and computerised cognitive training (CCT) behaviours. Facilitators for intervention acceptability included the provision of culturally tailored and personalised education, support from a trusted source, and inclusion of goal setting and self-monitoring behavioural strategies. CONCLUSIONS: While there was high acceptability for a brain health intervention, several barriers including cultural food norms and low self-efficacy for adopting the diet, exercise and CCT components would need to be considered in the intervention design. Findings from this study will be used to inform local decisions regarding the adaptation of FINGER for people with type 2 diabetes. The feasibility of the adapted multidomain intervention will then be evaluated in a future pilot trial.

Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA): health assessment protocol, participant profile and patterns of participation.

BACKGROUND: The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) is a prospective, longitudinal study of a representative cohort of older adults living in Northern Ireland, United Kingdom. Its aim is to explore the social, behavioural, economic and biological factors of ageing and how these factors change as people age. The study has been designed to maximize comparability with other international studies of ageing thereby facilitating cross-country comparisons. This paper provides an overview of the design and methodology of the health assessment which was carried out as part of Wave 1. METHODS: Three thousand, six hundred and fifty five community dwelling adults, aged 50 years and over participated in the health assessment as part of Wave 1 of NICOLA. The health assessment included a battery of measurements across various domains that addressed key indicators of ageing namely: physical function, vision and hearing, cognitive function, and cardiovascular health. This manuscript describes the scientific rationale for the choice of assessments, provides an overview of the core objective measures carried out in the health assessment and describes the differences in characteristics of participants who took part in the health assessment compared to those who did not take part. RESULTS: The manuscript highlights the importance of incorporating objective measures of health in population based studies as a means of complementing subjective measures and as a way to advance our understanding of the ageing process. The findings contextualize NICOLA as a data resource within Dementias Platform UK (DPUK), the Gateway to Global Ageing (G2G) and other existing networks of population based longitudinal studies of ageing. CONCLUSION: This manuscript can help inform design considerations for other population based studies of ageing and facilitate cross-country comparative analysis of key life-course factors affecting healthy ageing such as educational attainment, diet, the accumulation of chronic conditions (including Alzheimer's disease, dementia and cardiovascular disease) as well as welfare and retirement policies.

Food insecurity and brain health in adults: A systematic review.

Food insecurity has been associated with adverse effects on physical health and well-being in both high and low-income countries, but effects on brain health are not clear. The purpose of this systematic review was to determine the relationship between food insecurity and important brain health outcomes in adults including depression, stroke, cognitive impairment and dementia. Electronic databases were searched to find studies which investigated relations between food insecurity and predefined brain health outcomes. Thirty studies met the inclusion criteria for review of which 23 were conducted in high income countries and seven in low- or middle-income countries. Most studies (n = 24) were cross-sectional, five were prospective and 1 was a case-control design. Seven studies reporting outcomes relating to cognitive performance and 24 relating to depression. No studies investigated relations between food insecurity and stroke or dementia. There was substantial heterogeneity in the populations studied as well as measures of food insecurity and outcomes which made comparisons between studies difficult. Overall, the findings highlighted that individuals who were food insecure had increased likelihood of depressive symptoms and poorer global cognition than those who were food secure. It is possible that social support and food aid programmes attenuate the effects of food insecurity on depressive symptoms. Future research is needed to determine whether interventions to alleviate food insecurity can benefit brain health in vulnerable populations.

A systematic review of interventions to reduce anticholinergic burden in older people with dementia in primary care.

OBJECTIVE: This systematic review aimed to assess the types and effectiveness of interventions that sought to reduce anticholinergic burden (ACB) in people with dementia (PwD) in primary care. METHODS: One trial registry and eight electronic databases were systematically searched to identify eligible English language studies from inception until December 2021. To be eligible for inclusion, studies had to be randomised controlled trials (RCTs) or non-randomised studies (NRS), including controlled before-and-after studies and interrupted time-series studies, of interventions to reduce ACB in PwD aged ≥65 years (either community-dwelling or care home residents). All outcomes were to be considered. Quality was to be assessed using the Cochrane Risk of Bias tool for RCTs and ROBINS-I tool for NRS. If data could not be pooled for meta-analysis, a narrative synthesis was to be conducted. RESULTS: In total, 1880 records were found, with 1594 records remaining after removal of duplicates. Following title/abstract screening, 13 full-text articles were assessed for eligibility. None of these studies met the inclusion criteria for this review. Reasons for exclusion were incorrect study design, ineligible study population, lack of focus on reducing ACB, and studies conducted outside the primary care setting. CONCLUSIONS: This 'empty' systematic review highlights the lack of interventions to reduce ACB in PwD within primary care, despite this being highlighted as a priority area for research in recent clinical guidance. Future research should focus on development and testing of interventions to reduce ACB in this patient population through high-quality clinical trials.

Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study.

OBJECTIVE: To explore the role of chronic inflammation in rheumatoid arthritis (RA) on cognition. METHODS AND ANALYSIS: Six hundred sixty-one men and women aged ≥55 years who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA were recruited from three healthcare trusts in the United Kingdom (UK) between May 2018 and March 2020. Study participants took part in interviews which captured sociodemographic information, followed by an assessment of cognition. RA specific clinical characteristics were obtained from hospital medical records. Participants were cognitively assessed using the Montreal Cognitive Assessment (MoCA) and were classified as cognitively impaired if they scored ≤27/30 points. Linear regression analyses were conducted to identify which demographic and clinical variables were potential predictors of cognitive impairment. RESULTS: The average age of participants was 67.6 years and 67% (444/661) were women. 72% (458/634; 95% CI 0.69 to 0.76) of participants were classified as cognitively impaired (MoCA≤27). Greater cognitive impairment was associated with older age (p = .006), being male (p = .041) and higher disease activity score (DAS28) (with moderate (DAS28 > 3.1) (p = 0.008) and high (DAS28 > 5.1) (p = 0.008)) compared to those in remission (DAS28 ≤ 2.6). There was no association between MoCA score and education, disease duration, RF status, anti-cyclic citrullinated peptide (anti-CCP) status, RA medication type or use of glucocorticoids or non-steroidal anti-inflammatory drugs (p > 0.05). CONCLUSION: This study suggests that cognitive impairment is highly prevalent in older adults with RA. This impairment appears to be associated with higher RA disease activity and supports the concept that chronic systemic inflammation might accelerate cognitive decline. This underlines the importance of controlling the inflammatory response.

Association of renal impairment with cognitive dysfunction in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA).

INTRODUCTION: Chronic kidney disease (CKD) is a recognized risk factor for cognitive impairment. Identification of those at greatest risk of cognitive impairment may facilitate earlier therapeutic intervention. This study evaluated associations between estimated glomerular filtration rate (eGFR) and cognitive function in the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: Data were available for 3412 participants ≥50 years of age living in non-institutionalized settings who attended a health assessment between February 2014 and March 2016. Measures of serum creatinine (SCr) and cystatin C (cys-C) were used for eGFR. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). RESULTS: Following adjustment for potential confounders, a single unit decrease in eGFR was significantly associated with reduced cognitive function defined by an MMSE ≤24/30 {eGFR calculated using serum cys-C [eGFRcys]: ß = -0.01 [95% confidence interval (CI) -0.001 to -0.01], P = 0.01} and MoCA <26/30 [ß = -0.01 (95% CI -0.002 to -0.02), P = 0.02]. Similarly, CKD Stages 3-5 were also associated with a moderate increase in the odds of cognitive impairment (MMSE ≤24) following adjustment for confounders [eGFRcys: odds ratio 2.73 (95% CI 1.38-5.42), P = 0.004]. CONCLUSIONS: Decreased eGFRcys was associated with a significantly increased risk of cognitive impairment in a population-based cohort of older adults. However, there was no evidence of an association between cognitive impairment and the more commonly used eGFR calculated using SCr. eGFRcys may offer improved sensitivity over eGFRcr in the determination of renal function and associated risk of cognitive impairment.

Dietary patterns associated with renal impairment in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA).

BACKGROUND: Dietary-based primary prevention guidelines for chronic kidney disease (CKD) treatment are lacking due to limited evidence. Single nutrient intake studies do not account for complex dietary interactions. We assessed associations between dietary patterns and renal function in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA). DESIGN: A cross-sectional observational study used NICOLA baseline dietary data collected between February 2014 and March 2016 via a food frequency questionnaire for 2590 participants aged ≥ 50 years. Principal component analysis identified a posteriori dietary patterns. Renal function was characterised by estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin-C. Associations were assessed according to quintiles of dietary pattern adherence and multivariable regression analysis examined associations with eGFR. RESULTS: Variation in three dietary patterns was significantly associated with eGFR. After adjustment for potential confounders, participants with least adherence to the 'healthy' dietary pattern 1 had a mean eGFR 3.4 ml/min/1.73m2 (95% confidence interval, [CI] - 5.0, - 1.7, p < 0.001) lower than the most adherent. Those with lowest adherence to the 'unhealthy' dietary pattern 2 had a mean eGFR 1.9 ml/min/1.73m2 (CI 0.2, 3.5, p = 0.03) higher than those with highest adherence. Participants with lowest adherence to dietary pattern 3, characterised by a high consumption of alcohol and coffee, had a mean eGFR 1.8 ml/min/1.73m2 (- 3.5, - 0.01, p = 0.05) lower than those with greatest adherence. CONCLUSIONS: Our findings identify independent associations between dietary patterns and eGFR. These findings can inform the development of diet-related primary prevention advice for CKD.

Pharmacological treatment of hypertension in people without prior cerebrovascular disease for the prevention of cognitive impairment and 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.

Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia.

BACKGROUND: Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug - cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine - are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment. OBJECTIVES: To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer-related outcomes. SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. SELECTION CRITERIA: We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed citations and full-text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3-11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods. MAIN RESULTS: We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias. Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) -0.42, 95% confidence interval (CI) -0.64 to -0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD -0.40, 95% CI -0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD -0.62; 95% CI -0.94 to -0.31). Data from one longer-term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) -2.09 Standardised Mini-Mental State Examination (SMMSE) points, 95% CI -3.43 to -0.75; moderate certainty). Discontinuation may make little or no difference to functional status in the short term (SMD -0.25, 95% CI -0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD -0.38, 95% CI -0.74 to -0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD -3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI -6.67 to -0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD - 0.48, 95% CI -0.82 to -0.13; 2 studies; low certainty; and SMD -0.27, 95% CI -0.47 to -0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD -0.87 Neuropsychiatric Inventory (NPI) points; 95% CI -8.42 to 6.68; moderate certainty). We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review. AUTHORS' CONCLUSIONS: This review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well-designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.

Shaping a data-driven era in dementia care pathway through computational neurology approaches.

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.

The impact of oral rehabilitation coupled with healthy dietary advice on the nutritional status of adults: A systematic review and meta-analysis.

As natural teeth are lost, many older adults choose softer foods lacking in essential micronutrients and fiber, yet replacing missing teeth alone does not positively influence diet. Dietary intervention in combination with treatment to replace missing teeth is increasing, though understanding of effective intervention components is limited. This systematic review synthesized literature relating to oral rehabilitation coupled with dietary intervention in adults. The primary outcome was dietary intake; secondary outcomes pertained to oral health and dietary intervention characteristics including: theoretical basis and behavior change techniques (BCTs). MEDLINE, Web of Science, PubMed and CENTRAL were searched. Nine studies were included. Study designs were heterogeneous involving 526 participants. Narrative synthesis identified improvements in at least one aspect of participants' oral health (i.e. biting/chewing) alongside at least one positive diet/nutrition outcome post-intervention for all studies. F/V results were pooled for three studies using meta-analysis techniques resulting in a standardized mean difference (SMD) of 0.29 [CI -0.54, 1.12], p = 0.49, but with marked heterogeneity (p = 0.0007). Few interventions were theory-based and intervention components were poorly described. Overall, narrative synthesis indicated support for dietary intervention coupled with oral rehabilitation on diet. Meta-analysis was only possible with three studies highlighting limitations. Large-scale, appropriately described trial methodologies are needed.Trial registry: This review was prospectively registered with PROSPERO on the 11 July 2017 [CRD42017071075].

Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia.

BACKGROUND: Dementia is a worldwide concern. Its global prevalence is increasing. At present, there is no medication licensed to prevent or delay the onset of dementia. Inflammation has been suggested as a key factor in dementia pathogenesis. Therefore, medications with anti-inflammatory properties could be beneficial for dementia prevention. OBJECTIVES: To evaluate the effectiveness and adverse effects of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for the primary or secondary prevention of dementia. SEARCH METHODS: We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group up to 9 January 2020. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP) and six other databases to ensure that the searches were as comprehensive and up-to-date as possible. We also reviewed citations of reference lists of included studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing aspirin or other NSAIDs with placebo for the primary or secondary prevention of dementia. We included trials with cognitively healthy participants (primary prevention) or participants with mild cognitive impairment (MCI) or cognitive complaints (secondary prevention). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the strength of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included four RCTs with 23,187 participants. Because of the diversity of these trials, we did not combine data to give summary estimates, but presented a narrative description of the evidence. We identified one trial (19,114 participants) comparing low-dose aspirin (100 mg once daily) to placebo. Participants were aged 70 years or older with no history of dementia, cardiovascular disease or physical disability. Interim analysis indicated no significant treatment effect and the trial was terminated slightly early after a median of 4.7 years' follow-up. There was no evidence of a difference in incidence of dementia between aspirin and placebo groups (risk ratio (RR) 0.98, 95% CI 0.83 to 1.15; high-certainty evidence). Participants allocated aspirin had higher rates of major bleeding (RR 1.37, 95% CI 1.17 to 1.60, high-certainty evidence) and slightly higher mortality (RR 1.14, 95% CI 1.01 to 1.28; high-certainty evidence). There was no evidence of a difference in activities of daily living between groups (RR 0.84, 95% CI 0.70 to 1.02; high-certainty evidence). We identified three trials comparing non-aspirin NSAIDs to placebo. All three trials were terminated early due to adverse events associated with NSAIDs reported in other trials. One trial (2528 participants) investigated the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib (200 mg twice daily) and the non-selective NSAID naproxen (220 mg twice daily) for preventing dementia in cognitively healthy older adults with a family history of Alzheimer's disease (AD). Median follow-up was 734 days. Combining both NSAID treatment arms, there was no evidence of a difference in the incidence of AD between participants allocated NSAIDs and those allocated placebo (RR 1.91, 95% CI 0.89 to 4.10; moderate-certainty evidence). There was also no evidence of a difference in rates of myocardial infarction (RR 1.21, 95% CI 0.61 to 2.40), stroke (RR 1.82, 95% CI 0.76 to 4.37) or mortality (RR 1.37, 95% CI 0.78 to 2.43) between treatment groups (all moderate-certainty evidence). One trial (88 participants) assessed the effectiveness of celecoxib (200 mg or 400 mg daily) in delaying cognitive decline in participants aged 40 to 81 years with mild age-related memory loss but normal memory performance scores. Mean duration of follow-up was 17.6 months in the celecoxib group and 18.1 months in the placebo group. There was no evidence of a difference between groups in test scores in any of six cognitive domains. Participants allocated celecoxib experienced more gastrointestinal adverse events than those allocated placebo (RR 2.66, 95% CI 1.05 to 6.75; low-certainty evidence). One trial (1457 participants) assessed the effectiveness of the COX-2 inhibitor rofecoxib (25 mg once daily) in delaying or preventing a diagnosis of AD in participants with MCI. Median duration of study participation was 115 weeks in the rofecoxib group and 130 weeks in the placebo group. There was a higher incidence of AD in the rofecoxib than the placebo group (RR 1.32, 95% CI 1.01 to 1.72; moderate-certainty evidence). There was no evidence of a difference between groups in cardiovascular adverse events (RR 1.07, 95% CI 0.68 to 1.66; moderate-certainty evidence) or mortality (RR 1.62, 95% CI 0.85 to 3.05; moderate-certainty evidence). Participants allocated rofecoxib had more upper gastrointestinal adverse events (RR 3.53, 95% CI 1.17 to 10.68; moderate-certainty evidence). Reported annual mean difference scores showed no evidence of a difference between groups in activities of daily living (year 1: no data available; year 2: 0.0, 95% CI -0.1 to 0.2; year 3: 0.1, 95% CI -0.1 to 0.3; year 4: 0.1, 95% CI -0.1 to 0.4; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is no evidence to support the use of low-dose aspirin or other NSAIDs of any class (celecoxib, rofecoxib or naproxen) for the prevention of dementia, but there was evidence of harm. Although there were limitations in the available evidence, it seems unlikely that there is any need for further trials of low-dose aspirin for dementia prevention. If future studies of NSAIDs for dementia prevention are planned, they will need to be cognisant of the safety concerns arising from the existing studies.

CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study.

OBJECTIVE: To test the hypothesis that APOE ε4 status and cerebrospinal fluid (CSF) Aß42, T-tau and P-tau would independently predict the risk of postoperative delirium. BACKGROUND: Delirium following surgery is common and associated with adverse outcomes. Age and cognitive impairment are consistent risk factors for postoperative delirium. METHODS: This observational cohort study recruited 282 participants aged 65 years or older, without a diagnosis of dementia, admitted for primary elective hip or knee arthroplasty. Cognitive tests were undertaken preoperatively, blood and CSF were sampled at the time of spinal anesthesia, and participants were assessed daily postoperatively for delirium. RESULTS: Increasing age (P = 0.04), preoperative comorbidity (P = 0.03), type of surgery (P = 0.05), intravenous opioid usage (P = 0.04), and low CSF Aß42 (P < 0.01) were independent predictors of postoperative delirium. CONCLUSIONS: This study is the first to show an independent association between CSF Aß42 and delirium incidence in an elective surgical population, suggesting that postoperative delirium may indicate incipient Alzheimer disease.

The impact of dental status on perceived ability to eat certain foods and nutrient intakes in older adults: cross-sectional analysis of the UK National Diet and Nutrition Survey 2008-2014.

BACKGROUND: Many factors determine dietary intake in older adults, including physical health, psychological well-being and socio-economic status. Dental status may also be important. The aim was to examine how dental status impacts perceived ability to eat to certain foods, nutrient intake and nutritional status in UK older adults. METHODS: Data collected by the National Diet and Nutrition Survey Rolling Programme was analysed. A 4-day food diary assessed dietary intake, while a Computer Assisted Personal Interview collected socio-demographic, health behaviour and oral health information. Participants aged 65 years and over (n = 1053) were categorised into three groups according to their dental status: edentate with dentures (E-DEN, n = 292), dentate with dentures (D-DEN, n = 305) or dentate with no dentures (DEN, n = 456). A total of 515 participants provided a blood sample that was used to assess nutrient concentrations including vitamin B12, vitamin C, ferritin, vitamin B6 (pyridoxal-5-phosphate, PLP), retinol, ß-carotene and 25-hydroxyvitamin D (25-OH-D). Multiple regression methods were performed to examine cross-sectional associations between dental status, food selection, nutrient intake and nutritional status. RESULTS: Both E-DEN and D-DEN groups, compared with the DEN group, were more likely to report difficulty eating apples, raw carrots, lettuce, nuts, well-cooked steak and crusty bread (P < 0.01). No group differences were observed in perceived ability to eat sliced bread, sliced cooked meats and cheese. The E-DEN group compared with the DEN group had lower mean daily intakes of omega 3 fatty acids (P = 0.006), non-starch polysaccharides (P = 0.001), ß-carotene (P = 0.001), folate (P = 0.001), vitamin C (P = 0.008), magnesium (P < 0.001) and potassium (P < 0.001), and had lower plasma vitamin B6 PLP (P = 0.001), vitamin C (P = 0.009) and ß-carotene (P = 0.015) concentrations, after adjusting for socio-demographic and health behavioural factors. Compared with the DEN group, the D-DEN group did not have lower nutrient intakes or lower blood nutrient concentrations. CONCLUSIONS: Within this sample of older adults, impaired dental status appears to influence food selection, and intake of important nutrients. Future research should focus on developing dental interventions coupled with dietary counselling to encourage the adoption of healthy eating habits in this high-risk population group.

Effect of dietary interventions in mild cognitive impairment: a systematic review.

Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed, particularly in a mild cognitive impairment (MCI) population. This review examined the effect of diet on cognitive outcomes in MCI patients. A total of five databases were searched to find randomised controlled trial (RCT) studies, with diet as the main focus, in MCI participants. The primary outcome was incident dementia and/or Alzheimer's disease (AD) and secondary outcomes included cognitive function across different domains using validated neuropsychological tests. Sixteen studies met the inclusion criteria. There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making study comparisons difficult. Supplementation with vitamin E (one study, n 516), ginkgo biloba (one study, n 482) or Fortasyn Connect (one study, n 311) had no significant effect on progression from MCI to dementia and/or AD. For cognitive function, the findings showed some improvements in performance, particularly in memory, with the most consistent results shown by B vitamins, including folic acid (one study, n 266), folic acid alone (one study, n 180), DHA and EPA (two studies, n 36 and n 86), DHA (one study, n 240) and flavonol supplementation (one study, n 90). The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients. Further well-designed trials are needed, with standardised and robust measures of cognition to investigate the influence of diet on cognitive status.

Confocal infrared imaging with optical coherence tomography provides superior detection of a number of common macular lesions compared to colour fundus photography.

PURPOSE: To compare diagnostic accuracy of confocal infrared reflectance (IR), with and without optical coherence tomography (OCT), to colour fundus photography (CFP) in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) Study. METHODS: Cross-sectional observational study of participants in NICOLA. CFP, IR and IR/OCT of 640 eyes were graded for hard, soft and reticular pseudodrusen; geographic atrophy; choroidal neovascularisation; naevus; epiretinal membrane; and haemorrhages. Test characteristics (sensitivity and specificity) for each imaging modality with respect to each retinal feature were calculated. RESULTS: With CFP as the reference standard, sensitivity of IR by itself ranged from 75% for RPD to 93.5% for hard drusen and specificity was above 90% for all features except hard drusen (71.7%). For IR combined with OCT, sensitivity ranged from 80% for choroidal neovascularisation to 96.5% for hard drusen. When IR alone was the reference standard, CFP sensitivity was high for naevi (97.5%) but reduced markedly for epiretinal membrane (48.5%). When the combination of IR and OCT was the reference standard, sensitivity for CFP was least for epiretinal membrane (31.5%), low for geographic atrophy and reticular pseudodrusen (77.8% and 76.2% respectively) and high for all other lesion types. CONCLUSION: Our findings support the use of confocal IR with OCT as a screening tool for a variety of features of macular disease in community optometric practice.

Pisa syndrome due to donepezil: pharmacokinetic interactions to blame?

We report a case of Pisa syndrome (PS) due to the acetylcholinesterase inhibitor donepezil which may have been precipitated by pharmacokinetic interactions with commonly used medications. PS is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. This is a rare but very distressing complication with this commonly used medication which was not initially recognised, leading to increasing disability for the patient and significant carer stress. Cessation of donepezil and modulation of potential interacting medications resulted in complete resolution.

Observational cohort study examining apolipoprotein E status and preoperative neuropsychological performance as predictors of post-operative delirium in an older elective arthroplasty population.

Introduction: delirium following surgery is common and is associated with negative outcomes. Preoperative cognitive impairment has been shown to be a risk factor for post-operative delirium. Often the cognitive tests used are cumbersome. This study tests the hypothesis that the quantification of brain vulnerability, using Apolipoprotein E (ApoE) status and neuropsychological tests, both traditional and more easily administered, can quantify the risk of post-operative delirium following elective primary arthroplasty surgery. Methods: this observational cohort study recruited participants aged 65 years or older admitted prior to elective primary hip or knee arthroplasty. Baseline data was collected and participants underwent neuropsychological testing and had blood taken for ApoE genotyping preoperatively. Post-operatively participants were assessed daily for delirium using the Confusion Assessment Method (CAM) and charts were reviewed where possible for reports of delirium. Univariate and multivariate analyses of preoperative factors were undertaken to identify independent predictors of delirium. Results: between March 2012 and October 2014, 315 participants completed the study with an overall incidence of post-operative delirium of 40/315 (12.7%). Of these 18 fulfilled the CAM criteria for delirium and 22 were deemed delirious by consensus decision based on chart review. ApoE genotype was not associated with post-operative delirium in this cohort. Time taken to complete Colour Trails 2, errors in mini mental state examination and level of pain preoperatively were independent predictors of post-operative delirium. Conclusions: this study challenges the assertion that ApoE4 genotype predicts post-operative delirium. It replicates previous work suggesting cognitive impairment predicts post-operative delirium and shows for the 1st time that simple cognitive tests can be as effective as more detailed tests.

Statins for the prevention of dementia.

BACKGROUND: This is an update of a Cochrane review first published in 2001 and then updated in 2009. Vascular risk factors including high cholesterol levels increase the risk of dementia due to Alzheimer's disease and of vascular dementia. Some observational studies have suggested an association between statin use and lowered incidence of dementia. OBJECTIVES: To evaluate the efficacy and safety of statins for the prevention of dementia in people at risk of dementia due to their age and to determine whether the efficacy and safety of statins for this purpose depends on cholesterol level, apolipoprotein E (ApoE) genotype or cognitive level. SEARCH METHODS: We searched ALOIS (the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) Portal on 11 November 2015. SELECTION CRITERIA: We included double-blind, randomised, placebo-controlled trials in which statins were administered for at least 12 months to people at risk of dementia. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two trials with 26,340 participants aged 40 to 82 years of whom 11,610 were aged 70 or older. All participants had a history of, or risk factors for, vascular disease. The studies used different statins (simvastatin and pravastatin). Mean follow-up was 3.2 years in one study and five years in one study. The risk of bias was low. Only one study reported on the incidence of dementia (20,536 participants, 31 cases in each group; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.61 to 1.65, moderate quality evidence, downgraded due to imprecision). Both studies assessed cognitive function, but at different times using different scales, so we judged the results unsuitable for a meta-analysis. There were no differences between statin and placebo groups on five different cognitive tests (high quality evidence). Rates of treatment discontinuation due to non-fatal adverse events were less than 5% in both studies and there was no difference between statin and placebo groups in the risk of withdrawal due to adverse events (26,340 participants, 2 studies, OR 0.94, 95% CI 0.83 to 1.05). AUTHORS' CONCLUSIONS: There is good evidence that statins given in late life to people at risk of vascular disease do not prevent cognitive decline or dementia. Biologically, it seems feasible that statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising. However, indication bias may have been a factor in these studies and the evidence from subsequent RCTs has been negative. There were limitations in the included studies involving the cognitive assessments used and the inclusion of participants at moderate to high vascular risk only.