Associations of Cognitive Impairment with All-Cause and Cardiovascular Mortality Among Individuals with Diabetes: A Prospective Cohort Study.

This study explored the association between diabetes, cognitive imFpairment (CI), and mortality in a cohort of 2931 individuals aged 60 and above from the 2011 to 2014 NHANES. Mortality data was gathered through 2019, and multivariable Cox proportional hazards models were used to determine the association between diabetes, CI, and mortality adjusting for sociodemographic characteristics, lifestyle factors, and comorbidity conditions. The study spanned up to 9.17 years, observing 579 deaths, with individuals having both diabetes and CI showing the highest all-cause mortality (23.6 events per 100 patient-years). Adjusted analysis revealed a 2.34-fold higher risk of all-cause mortality for this group, surpassing those with diabetes or CI alone. These results held after a series of stratified and sensitivity analyses. In conclusion, CI was linked to higher all-cause mortality in individuals with diabetes, emphasizing the need to address cognitive dysfunction in diabetic patients.

Effect of blood pressure on mortality in patients with cognitive impairment: a prospective cohort study.

Background: Cognitive impairment is a prevalent condition that substantially elevates mortality rates among the elderly. The impact of hypertension on mortality in older adults with cognitive impairment is a subject of contention. This study aims to examine the influence of hypertension on both all-cause and CVD-specific mortality in elderly individuals experiencing cognitive impairment within a prospective cohort. Methods: This study encompassed 2,925 participants (weighted 53,086,905) aged 60 years or older from National Health and Nutrition Examination Survey (NHANES) spanning 2011-2014. Incidence of all-cause and CVD-specific mortality was ascertained through linkage with National Death Index records until 31 December 2019. Survival was performed employing the Kaplan-Meier method. Hazard ratios (HRs) were calculated via Cox proportional hazards regression models. Results: Over the follow-up period of up to 9.17 years [with a median (IQR) time to death of 6.58 years], equivalent to 18,731.56 (weighted 3.46 × 108) person-years, there were a total of 576 recorded deaths. Participants with CI exhibited a 1.96-fold higher risk of all-cause mortality (95% CI: 1.55-2.49; p < 0.01) and a 2.8-fold higher risk of CVD-specific mortality (95% CI: 1.83-4.29; p < 0.01) in comparison to participants without CI. Among participants with CI, concurrent hypertension comorbidity was linked to a 2.73-fold elevated risk of all-cause mortality (95% CI: 1.78-4.17; p < 0.01) and a 5.3-fold elevated risk of CVD-specific mortality (95% CI: 2.54-11.04; p < 0.01). Further stratified analyses revealed that the combined effects of hypertension and CI on all-cause and CVD-specific mortality were more pronounced in participants aged 60-69 years compared to those aged 70-80 years (p for interaction <0.01). The primary findings exhibited resilience across a series of sensitivity analyses. Conclusions: Participants with CI exhibited a markedly elevated risk of all-cause and CVD-specific mortality when coexisting with hypertension. Appropriate management of hypertension in patients with CI may be helpful in reducing the excess risk of death.

Effect of hearing aids on cognitive functions in middle-aged and older adults with hearing loss: A systematic review and meta-analysis.

Objective: The study aimed to examine the effects of hearing aids on cognitive function in middle-aged and older adults with hearing loss. Data sources and study selection: PubMed, Cochrane Library, and Embase were searched for studies published before 30 March 2022. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) were included in the search. Restriction was set on neither types, severity, or the time of onset of hearing impairment nor cognitive or psychiatric statuses. Data extraction and synthesis: Two independent reviewers extracted data and assessed the study quality of RCTs. Cognitive function outcomes were descriptively summarized and converted to standardized mean difference (SMD) in the meta-analysis. Meta-analysis was conducted in RCTs. Sub-group analyses were conducted by cognitive statuses, psychiatric disorders, and cognitive domains. Results: A total of 15 studies met the inclusion criteria, including five RCTs (n = 339) and 10 NRSIs (n = 507). Groups were classified as subjects without dementia or with normal global cognition, subjects with AD or dementia, and subjects with depressive symptoms. For subjects without dementia, improvements were found in global cognition, executive function, and episodic memory. For subjects with depressive symptoms, improvements were found in immediate memory, global cognition, and executive function. No improvement was found in subjects with AD or dementia. In total, four RCTs were included in the meta-analysis. For subjects without dementia (SMD = 0.11, 95% confidence interval [CI]: -0.15-0.37) and those with AD, no significant effect was found (SMD = -0.19, 95% CI: -0.65-0.28). For subjects without dementia, no significant effect was found in language (SMD = 0.14, 95% CI: -0.30-0.59) or general executive function (SMD = -0.04, 95% CI: -0.46-0.38). Further sub-group analysis found no significant effect in executive function (SMD = -0.27, 95% CI: -0.72-0.18) or processing speed (SMD = -0.02, 95% CI: -0.49-0.44). Conclusion: Hearing aids might improve cognitive performance in domains such as executive function in subjects without dementia. The effects on subjects with depressive symptoms remained unclear. No improvement was found in subjects with AD or dementia. Long-term RCTs and well-matched comparison-group studies with large sample sizes are warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022349057.

Differences in treatment for Alzheimer's disease between urban and rural areas in China.

Introduction: In China, the increasing number of people with Alzheimer's disease (AD) poses a great challenge to families and the country. Economic and cultural differences cause a urban-rural gap in medical resources. This multicenter survey aimed to investigate the real-world practice of disease treatment among people with AD. Methods: People with AD and their caregivers from 30 provincial regions in mainland China were enrolled from October 2020 to December 2020 to be surveyed for their treatment experience. Logistic regression was used to explore the factors that influence medication adherence in all areas, urban areas, and rural areas. Results: In this survey, 1,427 participants came from urban areas, and 539 participants came from rural areas. Patients in urban areas were older (mean age 74 vs. 70, p = 0.001), less frequently had mild AD (36.0 vs. 52.1%, p < 0.001), and more often were cared for at professional institutions (8.8 vs. 3.2%, p < 0.001). In terms of pharmacotherapy, 77.8% of people accepted taking lifelong medication, whereas 61.3% of patients insisted on taking medications. Although 72.0% of rural people believed in taking lifelong medication, only 30.0% adhered to drug use. The major factors that influenced medication adherence for all patients with AD were regional distribution (p < 0.001, OR = 6.18, 95% CI: 4.93-7.74) and family earnings (p = 0.003, OR = 1.22, 95% CI: 1.07-1.38). In rural areas, family earnings (p = 0.008, OR = 1.44, 95% CI: 1.10-1.89) and severity of AD (p = 0.033, OR = 1.31, 95% CI: 1.02-1.68) were the main factors. Family earnings (p = 0.038, OR = 1.16, 95% CI: 1.01-1.34) was the only factor among urban areas. Among all non-pharmaceutical activities except for cognitive intervention, the participation rates of rural patients were significantly higher than those of urban patients (p < 0.05). Conclusion: Although national progress has been made in the public awareness of disease treatment, adequate diagnosis and medication adherence need to be prompted, especially in rural areas. Furthermore, lifelong treatment should be improved based on regional characteristics through the joint efforts of the government, health workers, and social volunteers.

In vivo imaging of tau deposition in Alzheimer's disease using both [18F]-THK5317 and [18F]-S16: A pilot human study.

Objective: To evaluate the effectiveness of a new tracer (S)-1-(4-(6-(dimethylamino)quinoxalin-2-yl)phenoxy)-3-fluoropropan-2-ol ([18F]-S16), in distinguishing patients with AD from HCs. Methods: Paired [18F]-S16 and [18F]-THK5317 scans were acquired in five patients with AD, six HCs, one subject with a semantic variant of primary progressive aphasia (sv-PPA) and one subject with probable progressive supranuclear palsy (PSP). Dynamic PET scanning was performed over 90 min after injection of the tracers. Standardized uptake values (SUV) and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were used for tau deposition semi-quantization. A voxel-based analysis was employed to assess the uptake difference between populations. Results: [18F]-S16 exhibited excellent blood-brain-barrier penetration. AD patients showed increased cortical [18F]-THK5317 and [18F]-S16 binding. Compared to HCs, AD patients showed significantly increased cortical [18F]-S16 uptake in the bilateral occipital cortex, posterior cingulated cortex/precuneus, and lateral frontal cortex. Notable [18F]-S16 uptake was observed in the basal ganglia and brainstem compared to the neocortex. A substantial [18F]-S16 signal was detected in the basal ganglia and midbrain in a patient with probable PSP and in the bilateral anterior temporal cortex in a sv-PPA patient. Conclusion: [18F]-S16 might be of help to detect tau protein in vivo.

Plasma repressor element 1-silencing transcription factor levels are decreased in patients with Alzheimer's disease.

BACKGROUND: Repressor element 1-silencing transcription (REST)/neuron-restrictive silencer factor is considered a new therapeutic target for neurodegenerative disorders such as Alzheimer's disease (AD). However, the relationship between AD and REST remains unclear. This study aimed to 1) examine plasma REST levels and REST gene levels in AD patients and 2) further explore the pathological relationships between REST protein levels and cognitive decline in clinical conditions, including medial temporal lobe atrophy. METHODS: Participants (n = 252, mean age 68.95 ± 8.78 years) were recruited in Beijing, China, and then divided into a normal cognition (NC) group (n = 89), an amnestic mild cognitive impairment (aMCI) group (n = 79), and an AD dementia group (n = 84) according to diagnostic criteria. All participants underwent neuropsychological assessments, laboratory tests, and neuroimaging scans (magnetic resonance imaging) at baseline. Plasma REST protein levels and the distribution of REST single nucleotide polymorphisms (SNPs) were compared among the three groups. Correlations between cognitive function, neuro-imaging results, and REST levels were determined by a multivariate linear regression analysis. RESULTS: The plasma REST levels in both the NC group (430.30 ± 303.43)pg/ml and aMCI group (414.27 ± 263.39)pg/ml were significantly higher than that in the AD dementia group (NC vs AD dementia group, p = 0.034; aMCI vs AD dementia group, p = 0.033). There was no significant difference between the NC and aMCI groups (p = 0.948). No significant difference was found among the three groups regarding the genotype distribution (rs2227902 and rs3976529 SNPs) of the REST gene. The REST level was correlated with the left medial temporal lobe atrophy index (r = 0.306, p = 0.023). After 6 months of follow-up, the REST level in the NC group was positively correlated with the change in the Mini-Mental State Examination score (r = 0.289, p = 0.02). CONCLUSION: The plasma REST protein level is decreased in AD dementia patients, which is associated with memory impairment and left temporal lobe atrophy and may have potential value for clinical diagnosis of AD dementia.

Factors Associated With Alzheimer's Disease Patients' Caregiving Status and Family Caregiving Burden in China.

Background: The increasing prevalence of Alzheimer's disease (AD) has emerged as a major challenge worldwide. China as the most populous country in the globe is amid rapid aging of its population, highlighting the need for appropriate social and medical policies to meet the challenge. The current multicenter cross-sectional observational study aims to provide understanding of the current status of caring given to AD patients in China and investigate the factors that influence the family burden as well as the choice of care given to AD patients. Methods: A total of 1,675 patients with probable AD from 30 provincial regions of mainland China were enrolled in the current study from August 2019 to December 2019. We analyzed the caregiving status and its relationship with family burden and various socio-economical and medical factors. Results: In the current study, 90.87% of the AD patients enrolled adopted family care. The choice of caregiving method was influenced by factors including age (>80 years old, OR 0.648; 95% CI, 0.427-0.983), overall family burden (high, OR 0.574; 95% CI, 0.0.373-0.884), patients' income (OR 0.511; 95% CI, 0.330-0.789) and self-care ability (OR 0.329; 95% CI, 0.183-0.588). Conclusion: Family care is the primary method of care for AD patients in China and the institutional care system for AD patients is still underprepared in China.

Functional Abnormality Associated With Tau Deposition in Alzheimer's Disease - A Hybrid Positron Emission Tomography/MRI Study.

Objective: To investigate the characteristics of tau deposition and its impact on functional connectivity (FC) in Alzheimer's disease (AD). Methods: Hybrid PET/MRI scans with [18F]-THK5317 and neuropsychological assessments were undertaken in 26 participants with AD and 19 healthy controls (HC). The standardized uptake value ratio (SUVR) of [18F]-THK5317 PET imaging was compared between the AD and HC groups. Significant clusters that revealed higher tau deposition in the AD group compared to the HC group were selected as regions of interest (ROI) for FC analysis. We evaluated the difference in the FC between the two groups for each ROI pair. The clinical and radiological characteristics were compared between the AD patients with negative FC and AD patients with positive FC for exploratory analysis. Results: The bilateral inferior lateral temporal lobe, dorsal prefrontal cortex, precuneus, posterior cingulate cortex, hippocampus, and occipital lobe showed significantly higher [18F]-THK5317 accumulation in AD patients. Decreased FC in regions with higher SUVR was observed in AD patients, and the FC strength was negatively correlated with regional SUVR. Patients with a positive FC exhibited older ages, better cognitive performances, and a lower SUVR than patients with a negative FC. Conclusions: An impact of tau deposition was observed on FC at the individual level in AD patients. Our findings suggested that the combination of tau-PET and rs-fMRI might help predict AD progression.

A comparison of the diagnostic accuracy of the Mini-Cog and AD8 in identifying cognitive impairment in a geriatric health screening population in China.

The present study aimed to evaluate and compare the discriminative abilities of the Mini-Cog and AD8 tests in detecting cognitive impairment in a Chinese health screening population. 160 geriatric participants were enrolled at an academic medical center . The Mini-Cog, AD8, and Mini-Mental State Examination (MMSE) were used to assess the possibility of cognitive impairment. Logistic regression and receiver operator characteristic curve analyses were performed to evaluate the discriminative abilities of the tests. The prevalence of cognitive impairment was 41.25%. Logistic regression modeling showed that the Mini-Cog (odds ratio (OR) = 0.34, 95% confidence interval (CI): 0.25-0.46) and MMSE (OR = 0.58, 95%CI: 0.49-0.69) predicted cognitive impairment with 79.4% and 80.6% correct classification, respectively. While the AD8 (OR = 1.56, 95% CI: 1.32-1.85) predicted cognitive impairment with 72.5% correct classification. The areas under the receiver operating characteristic curves of the Mini-Cog, AD8 and MMSE for detecting cognitive impairment were 0.79 (95% CI: 0.72-0.85), 0.66 (95% CI: 0.58-0.73) and 0.80 (95% CI: 0.73-0.86). Both sensitivity and specificity of the Mini-Cog were superior to those of the AD8 (sensitivity 78.79% vs. 56.06%; specificity 79.79% vs. 75.53%). Cognitive screening is crucial to maintain the quality of life of older adults. Compared with the AD8, the Mini-Cog test is a more effective tool for screening cognitive impairment in older adults.

Associations of sarcopenia and its defining components with cognitive function in community-dwelling oldest old.

BACKGROUND: This study aimed to investigate the associations of sarcopenia and its defining components with cognitive function in community-dwelling oldest old (over 80 years old) in China. METHODS: Sarcopenia was diagnosed by the 2019 Asian Working Group for Sarcopenia (AWGS) criteria. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Logistic and linear regression models were used to explore the associations of sarcopenia and its defining components with risk of mild cognitive impairment (MCI), and performance on multiple cognitive domains among 428 adults aged 80 years and older. RESULTS: The overall prevalence of sarcopenia was 35.5%, with 40.34% for men and 32.14% for women. The prevalence of MCI was higher among sarcopenic oldest old than non-sarcopenic oldest old (28.95% vs. 17.39%, p = 0.005). Multivariate logistic regression analyses showed that sarcopenia [odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.04-3.33], low handgrip strength (HS) [OR = 2.33, 95% CI: 1.40-3.87] and slow gait speed (GS) [OR = 2.31, 95% CI: 1.13-4.72] were significantly and independently associated with risk of MCI. Multivariate linear regression analyses showed that low HS was associated with worse performance in global cognitive function, visuospatial and executive function, naming and delayed recall. CONCLUSIONS: Sarcopenia, low HS and low GS was significantly associated with MCI in community-dwelling oldest old. The associations between sarcopenia and its defining components with different cognitive subdomains could be further explored in the future.

Dietary vitamin intake and risk of metabolic syndrome among centenarians in China.

The present study aimed to investigate dietary vitamin intake levels and their association with the prevalence of obesity, hypertension, dyslipidemia and hyperglycemia in centenarians in China. From June 2014 to December 2016, a total of 992 centenarians aged >99 years (177 males and 815 females; age range, 100-115 years) were enrolled through household visits in the cities and rural areas of Hainan province. Details regarding food intake were recorded by continuous collection of 7-day food frequency and 24-h dietary review, and dietary vitamin intake levels were calculated according to the Chinese Food Composition Table. The deficiency rates of vitamin A (VA), VE, VB1, VB2, niacin and VC among the centenarians were relatively high and the prevalence of metabolic syndrome (MS) was 53.67% (519/967). The dietary intake levels of VA, VE and PP were significantly higher among the healthy centenarians than among the centenarians with MS (P<0.05). Compared with the lowest quartiles (Q1) of dietary vitamin intake, higher dietary intake levels of VA (Q4) [odds ratio (OR)=0.72; 95% CI: 0.38, 0.99], VE (Q3) (OR=0.61; 95% CI=0.36, 0.88) and VB2 (Q4) (OR=0.51; 95% CI: 0.32, 0.81) were associated with a reduced risk of hypertension (P<0.05). However, higher dietary intake levels of VA, VE, VB2 and PP were associated with increased risks of central obesity, hyperglycemia and low high-density lipoprotein cholesterol levels. A high prevalence of MS and vitamin deficiency were detected among the centenarians and these two items were associated with each other. It was indicated that specific vitamins are necessary for certain centenarians.

Diagnostic Accuracy of the Chinese Version of the Trail-Making Test for Screening Cognitive Impairment.

BACKGROUND/OBJECTIVES: The Trail-Making Test (TMT), which is commonly used to measure executive function, consists of two components (TMT-A and TMTB). There is a lack of normative TMT data for Chinese elderly adults. This study aimed to evaluate the validity of the TMT in screening for cognitive impairment. DESIGN: 2,294 Chinese-speaking adults aged 50 to 85: 1,026 with normal cognition (NC), 462 with mild cognitive impairment (MCI), 108 with Alzheimer's disease (AD), 113 with vascular mild cognitive impairment (VaMCI), 121 with vascular dementia (VaD), 282 with uncertain types of dementia, and 15 with mixed dementia. Receiver operating characteristic curve analysis was performed to test the ability of TMT scores to differentiate between NC and cognitive impairment. RESULTS: Age, education, and sex were significantly associated with TMT completion time. The TMT-A exhibited sensitivity of 77.8% and specificity of 92.0% with cut-off value of 98.5 seconds for discriminating AD from NC. The TMT-B had sensitivity of 83.3% and specificity of 91.8% with a cut-off value of 188.5 seconds for discriminating AD from NC. The TMT-A had sensitivity of 85.7% and specificity of 81.6% for discriminating NC from VaD with a cut-off value of 77.5 seconds, and the TMT-s had sensitivity of 81.6% and specificity of 83.9% with a cut-off value of 147.5 seconds. The TMT had less sensitivity distinguishing MCI from NC. CONCLUSION: The Chinese version of the TMT is reliable for detecting AD or VaD but poor at distinguishing MCI from NC.

Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II multicenter randomised controlled trial.

Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.

Development and validation of the geriatric depression inventory in Chinese culture.

BACKGROUND: Depression among older adults is under-recognized either in the community or in general hospitals in Chinese culture. This study aimed to develop a culturally appropriate screening instrument for late-life depression in the non-psychiatric settings and to test its reliability and validity for a diagnosis of depression. METHODS: Using a Delphi method, we developed a geriatric depression inventory (GDI), consisting of 12 core symptoms of depressive disorder in old age. We investigated its reliability and validity on 89 patients with late-life depression and 249 non-depression controls. Both self-report (GDI-SR) and physician-interview (GDI-RI) versions were assessed. RESULTS: Cronbach's α coefficient was 0.843 for GDI-SR and 0.880 for GDI-RI. Both GDI-SR and GDI-RI showed good concurrent validity with the 15-item Geriatric Depression Scale (GDS-15) (GDI-SR: r = 0.750, p < 0.001; GDI-RI: r = 0.733, p < 0.001). The area under the curve of the receiver operating characteristic (ROC) was 0.938 for GDI-SR and 0.961 for GDI-RI, suggesting good to excellent discrimination of depression versus non-depression. Using a cut-off of three items endorsed, sensitivity and specificity were 92.1% and 81.9% for GDI-SR, and 93.3% and 87.1% for GDI-RI. CONCLUSIONS: The GDI, either based on self-report or rater interview, is a reliable and valid instrument for the detection of depression among older adults in non-psychiatric medical settings in Chinese culture.

Utility of AD8 for cognitive impairment in a Chinese physical examination population: a preliminary study.

OBJECTIVE: To investigate the utility of AD8 for cognitive impairment in a Chinese physical examination population. METHODS: Military cadres who took routine physical examination in Chinese PLA General Hospital from Jan 1, 2013, to Dec 31, 2013, were subjected to AD8 scale. Individual information such as age, gender, and education was also collected. All data were analyzed by SPSS 19.0. RESULTS: 1544 subjects were enrolled in this study with mean age 75.4 ± 10.6 years. The subjects who scored 0 to 8 of AD8 scale were 1015, 269, 120, 60, 30, 14, 19, 8, and 9, respectively. Corresponding proportions were 65.7%, 17.4%, 7.8%, 3.9%, 2.0%, 0.9%, 1.2%, 0.5%, and 0.6%, respectively. The endorsement prevalence of 8 questions was 5.6%, 9.2%, 6.6%, 9.2%, 4.8%, 4.5%, 8.9%, and 24.1%, respectively. The endorsement prevalence of question 8 was significantly higher than others (P < 0.05). 260 subjects were scored equal to or greater than 2. The abnormal rate was 16.9%. All the participants were stratified into 9 groups by age; the prevalence of dementia was highly correlated with age (P < 0.01). CONCLUSION: AD8 scale is a convenient and effective tool for cognitive screening in routine physical examination population.

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.

BACKGROUND AND OBJECTIVES: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.