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AimsType 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.MethodsFocus 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.ResultsThere 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.ConclusionsWhile 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.

This is a conference abstract from the Alzheimer's Association International Conference 2019 in Los Angeles, California from 14-18 July 2019.

This is a conference abstract from the Alzheimer's Association International Conference in Los Angeles, California from 14-18 July 2019.

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.

Objective There is a widely recognised need to develop effective Alzheimer's disease (AD) biomarkers to aid the development of disease-modifying treatments, to facilitate early diagnosis and to improve clinical care. This overview aims to summarise the utility of key neuroimaging and cerebrospinal fluid (CSF) biomarkers for AD, before focusing on the latest efforts to identify informative blood biomarkers. Design A literature search was performed using PubMed up to September 2011 for reviews and primary research studies of neuroimaging (magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography and amyloid imaging), CSF and blood-based (plasma, serum and platelet) biomarkers in AD and mild cognitive impairment. Citations within individual articles were examined to identify additional studies relevant to this review. Results Evidence of AD biomarker potential was available for imaging techniques reflecting amyloid burden and neurodegeneration. Several CSF measures are promising, including 42 amino acid β-amyloid peptide (Aβ42); total tau (T-tau) protein, reflecting axonal damage; and phosphorylated tau (P-tau), reflecting neurofibrillary tangle pathology. Studies of plasma Aβ have produced inferior diagnostic discrimination. Alternative plasma and platelet measures are described, which represent potential avenues for future research. Conclusions Several imaging and CSF markers demonstrate utility in predicting AD progression and determining aetiology. These require standardisation before forming core elements of diagnostic criteria. The enormous potential available for identifying a minimally-invasive, easily-accessible blood measure as an effective AD biomarker currently remains unfulfilled. Copyright © 2012 John Wiley & Sons, Ltd.

Objectives This review aimed to assess the clinical efficacy and tolerability of statins in the treatment of dementia. Methods We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (27 October 2008). Double-blind, randomized controlled trials of statins given for at least 6 months in people with a diagnosis of dementia were included. Two independent authors extracted and assessed data independently against the inclusion criteria. Data were pooled where appropriate and entered into a meta-analysis. Results Three studies were identified (748 participants, age range 50–90 years). All patients had a diagnosis of probable or possible Alzheimer's disease according to standard criteria, and most patients were established on a cholinesterase inhibitor. Change in Alzheimer's Disease Assessment Scale cognitive subscale from baseline was a primary outcome in three studies; when data were pooled, statins did not provide any beneficial effect in this cognitive measure (mean difference −1.12; 95% confidence interval −3.99, 1.75; p = 0.44). All studies provided a change in Mini-Mental State Examination from baseline; there was no significant benefit from statins in this cognitive measure when the data were pooled (mean difference −1.53; 95% confidence interval −3.28; 0.21, p = 0.08). There were no studies identified assessing the role of statins in treatment of vascular dementia. There was no evidence that statins were detrimental to cognition. Conclusions There is insufficient evidence to recommend statins for the treatment of dementia. Copyright © 2012 John Wiley & Sons, Ltd.

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.

Background The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD, β-amyloid protein (Aβ) is deposited in the form of extracellular plaques and previous studies have determined Aβ generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction, it is biologically plausible they may be efficacious in the treatment of AD and VaD. Objectives To assess the clinical efficacy and safety of statins in the treatment of AD and VaD. To evaluate if the efficacy of statins in the treatment of AD and VaD depends on cholesterol level, 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 and LILACS, as well as many trials registries and grey literature sources (20 January 2014). Selection criteria Double-blind, randomised controlled trials of statins given for at least six months in people with a diagnosis of dementia. Data collection and analysis Two independent authors extracted and assessed data against the inclusion criteria. We pooled data where appropriate and entered them into a meta-analysis. We used standard methodological procedures expected by The Cochrane Collaboration. Main results We identified four studies (1154 participants, age range 50 to 90 years). All participants had a diagnosis of probable or possible AD according to standard criteria and most participants were established on a cholinesterase inhibitor. The primary outcome in all studies was change in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) from baseline. When we pooled data, there was no significant benefit from statin (mean difference -0.26, 95% confidence interval (CI) -1.05 to 0.52, P value = 0.51). All studies provided change in Mini Mental State Examination (MMSE) from baseline. There was no significant benefit from statins in MMSE when we pooled the data (mean difference -0.32, 95% CI -0.71 to 0.06, P value = 0.10). Three studies reported treatment-related adverse effects. When we pooled data, there was no significant difference between statins and placebo (odds ratio 1.09, 95% CI 0.58 to 2.06, P value = 0.78). There was no significant difference in behaviour, global function or activities of daily living in the statin and placebo groups. We assessed risk of bias as low for all studies. We found no studies assessing role of statins in treatment of VaD. Authors' conclusions Analyses from the studies available, including two large randomised controlled trials, indicate that statins have no benefit on the primary outcome measures of ADAS-Cog or MMSE.

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.

Objective: To compare performance of patients with mild-moderate Alzheimer's disease (AD) and vascular dementia (VaD) on tests of executive functioning and working memory.Methods: Patients with AD (n = 76) and VaD (n = 46) were recruited from a memory clinic along with dementia free participants (n = 28). They underwent specific tests of working memory from the Cognitive Drug Research (CDR) battery and pen and paper tests of executive function including CLOX 1 & 2, EXIT25 and a test of verbal fluency (COWAT). All patients had a CT brain scan which was independently scored for white matter change/ischaemia.Results: The AD and VaD groups were significantly impaired on all measures of working memory and executive functioning compared to the disease free group. There were no significant differences between the AD and VaD groups on any measure. Z-scores confirmed the pattern of impairment in executive functioning and working memory was largely equivalent in both patient groups. Small to moderate correlations were seen between the MMSE and the neurocognitive scores in both patient groups and the pattern of correlations was also very similar in both patient groups.Conclusions: This study demonstrates sizeable executive functioning and working memory impairments in patients with mild-moderate AD and VaD but no significant differences between the disease groups. Copyright (C) 2009 John Wiley & Sons, Ltd.