Reduction Of Cognitive Decline Research Articles

The Relevance of Phytate for the Treatment of Chronic Kidney Disease.

Diets high in plant-based foods are commonly recommended for people with chronic kidney disease (CKD). One putative advantage of these diets is reduced intestinal phosphate absorption. This effect has been ascribed to phytic acid (myoinositol hexaphosphoric acid) and its anion, phytate, that are present in many plant foods, particularly in the seeds, nuts, grains and fruits of plants. This paper reviews the structure and many actions of phytate with particular reference to its potential effects on people with CKD. Phytate binds avidly to and can reduce gastrointestinal absorption of the phosphate anion and many macrominerals and trace elements including iron, zinc, calcium and magnesium. This has led some opinion leaders to label phytate as an "anti-nutrient." The human intestine lacks phytase; hence, phytate is essentially not degraded in the small intestine. A small amount of phytate is absorbed from the small intestine, although phytate bound to phosphate is poorly absorbed. Clinical trials in maintenance hemodialysis patients indicate that intravenously administered phytate may decrease hydroxyapatite formation, vascular calcification and calciphylaxis. Orally administered phytate or in vitro studies indicate that phytate may also reduce osteoporosis, urinary calcium calculi formation and dental plaque formation. Phytate appears to have anti-inflammatory and antioxidant effects, at least partly due to its ability to chelate iron. Other potential therapeutic roles for phytate, not definitively established, include suppression of cancer formation, reduction in cognitive decline that occurs with aging, and amelioration of certain neurodegenerative diseases and several gastrointestinal and metabolic disorders. These latter potential benefits of phytate are supported by cell or animal research or observational studies in humans. Many of the above disorders are particularly common in CKD patients. Definitive clinical trials to identify potential therapeutic benefits of phytate in CKD patients are clearly warranted.

Older adults, cognitively stimulating activities and change in cognitive function

ABSTRACT Finding interventions which can address the decline of cognitive function as people get older is of great importance to policy-makers, especially in post-industrial societies with rapidly ageing populations. We examine the impact of several different types of mentally stimulating activities on cognitive function in a sample of community-dwelling Europeans aged 50 and older. The data were drawn from the fourth, fifth and sixth waves of the Survey on Health, Ageing and Retirement in Europe (SHARE). The activities analysed include non-formal learning activities such as education and training courses; informal learning activities such as reading books, newspapers and magazines; and some other types of cognitively stimulating activities including crossword puzzles and playing chess or card games. The cognitive function outcomes under investigation were memory and verbal fluency. Our longitudinal analysis of data on these older adults show that all the activities constituted a potential source for the delay or reduction of cognitive decline, even after a short period – only 4 years – of engagement in such activities and regardless of their age.

Perspective on the relationship between microbiota dysbiosis and neuroinflammation: probiotics as a treatment option.

Perspective on the relationship between microbiota dysbiosis and neuroinflammation: probiotics as a treatment option.

RADI-02. Hippocampal-sparing whole brain volumetric modulated arc therapy (VMAT) planning in Monaco: a “How-to” not pull your hair out

PurposeNRG-CC001 recently reported positive results on hippocampal-sparing IMRT (HS-IMRT) in conjunction with memantine for the reduction in cognitive decline compared to conventional whole brain radiation therapy. Herein, we report our experience in planning volumetric modulated arc therapy (VMAT) cases in Monaco® with the anticipation of increased utilization of the planning technique for delivery on Elekta linear accelerators.Methods and MaterialsTwelve patients previously treated with whole brain radiation therapy who would have been eligible for NRG-CC001 were replanned with VMAT HS-IMRT for to a dose of 30Gy/10fx using constraints from the trial.ResultsAll twelve patients were able to be planned with VMAT and achieve NRG-CC001 dose constraints. Median maximum and D100% to the right and left hippocampi were: 13.37Gy and 13.43Gy, respectively and 8.76Gy and 8.86Gy, respectively. Median coverage of the brain minus the hippocampi with 30Gy was 96.53%. All cases passed quality assurance testing with 3%/3mm and 2%/2mm criterion.ConclusionsHippocampal-sparing IMRT whole brain radiation therapy can be feasibly planned with VMAT technique in Monaco® and delivered on Elekta linear accelerators.

Association Between Metformin and Prevention of Dementia in T2DM Adult Patients

Introduction: In 2020 the World Health Organization estimated that the number of people with dementia was 50 million in the world. Furthermore, it is expected about 10 million new cases every year. Alzheimer’s disease (AD) is the most common form of dementia, which represents more than 50% of the cases. Type 2 diabetes mellitus (T2DM) is a major risk factor for AD and dementia. Even in people without clinical dementia, diabetes is associated with decreased cognitive performance and with increased brain atrophy. If comparing general population and people with diabetes, patients with T2DM had a 73% higher risk of developing dementia and a 56% increased risk of developing AD. Typically, the first medication prescribed for T2DM is metformin and it has been associated with the reduction of cognitive decline and the risk of dementia in patients with T2DM when compared with diabetic patients without medication. A randomized, double-blinded, placebo-controlled study demonstrated that during metformin treatment there was an improvement of executive functioning, learning, memory, and attentional abilities. A possible explanations for the protective effect of metformin in patients with T2DM is that it prevents hyperinsulinemia and the formation of amyloid-β plaques in the brain and the onset of AD. Metformin does not only decrease the plasma glucose level in several mechanisms, but it also characterized to beneficially effect serum lipid profiles, reduce inflammatory cell adhesion to endothelium, and exert anti-inflammatory, anti-apoptotic and anti-oxidative properties. Method: A Clinical Scientific Research was made about correlation among dementia and metformin. Were searched and found in PubMed a total of 61 articles between 2015–2020, but only free access and those who correlated metformin and dementia were used. Results: Studies showed that T2DM patients taking metformin had decreased risk of developing dementia or AD if compared to others diabetic patients that were not taking metformin. However, it is being hard to test antidiabetic therapies in AD, because the mechanisms which tie T2DM to Alzheimer clinical syndrome are not totally known. Therefore, to be as effective as possible it is necessary to treat the patients before they develop extensive amyloid and tau tangle burden. Conclusion: Diabetic patients taking metformin have a protector factor to don’t develop dementia or AD, when compared to those who don’t take metformin since they started the treatment before accumulation of amyloid and tau protein in the brain.

Hippocampal-sparing whole brain volumetric modulated arc therapy (VMAT) planning in Monaco: a "How-to" not pull your hair out.

NRG-CC001 recently reported positive results on hippocampal-sparing IMRT (HS-IMRT) in conjunction with memantine for the reduction in cognitive decline compared to conventional whole brain radiation therapy. Herein, we report our experience in planning volumetric modulated arc therapy (VMAT) cases in Monaco® with the anticipation of increased utilization of the planning technique for delivery on Elekta linear accelerators. Twelve patients previously treated with whole brain radiation therapy who would have been eligible for NRG-CC001 were replanned with VMAT HS-IMRT for to a dose of 30Gy/10fx using constraints from the trial. All 12 patients were able to be planned with VMAT and achieve NRG-CC001 dose constraints. Median maximum and D100% to the right and left hippocampi were: 13.37Gy and 13.43Gy, respectively and 8.76Gy and 8.86Gy, respectively. Median coverage of the brain minus the hippocampi with 30Gy was 96.53%. All cases passed quality assurance testing with 3%/3 mm and 2%/2 mm criterion. Hippocampal-sparing IMRT whole brain radiation therapy can be feasibly planned with VMAT technique in Monaco® and delivered on Elekta linear accelerators.

Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia.

BackgroundVitamin B12 deficiency is linked to impaired cognition and memory along with a sensation of tingling and numbness, an outcome of poor myelination. Elevated methylmalonic acid and serum homocysteine levels are markers of Vitamin B12 deficiency. Elevated homocysteine levels are also often associated with Alzheimer’s disease and stroke. We conducted this study to determine the effect of vitamin B12 replacement therapy on vitamin B12-deficient patients with noted cognitive impairment.MethodsWe conducted a cross-sectional, multicenter study of patients with minimal cognitive impairment (MCI) to assess for Vitamin B12 and homocysteine levels. All patients found to be deficient in vitamin B12 underwent replacement therapy and were assessed again after three months via the Mini-Mental State Examination (MMSE) and a review of symptoms.ResultsA total of 202 patients were included in the study. Of those, 171 (84%) patients reported marked symptomatic improvement after vitamin B12 replacement while MMSE scores improved in 158 (78%) patients. Of the remaining 44 patients who reported no symptomatic improvement, MMSE scores improved in 26 while 18 patients showed no MMSE score improvements.ConclusionsVitamin B12 deficiency is linked to cognition, and replacement therapy may be an option to improve patient cognition outcomes. Further studies are needed to confirm and refine the observed associations over a larger scale and to determine whether these findings will translate to a reduction in cognitive decline.

DIFFERENTIAL EFFECTS OF PHARMACOLOGIC AND NON-PHARMACOLOGIC TREATMENTS OF ALZHEIMER’S DISEASE: A COMPREHENSIVE SUMMARY OF EVIDENCE AND META-ANALYSIS

The objective of any Alzheimer's disease (AD) treatment is to achieve clinically meaningful symptom reductions without compromising the quality of life (QOL) in patients. Despite the promise of emerging therapies, existing pharmacological treatments have dominated the AD treatment landscape. The acceptance of these treatment norms, especially in comparison to non-pharmacological treatments has not been adequately examined. We performed an exhaustive, quantitative review of their comparative effects, based on all published clinical data, which has not been methodologically feasible until now. This investigation applies novel clinical data extraction and aggregation technologies developed by MedAware Systems, Inc. It is a patent-pending process where two scientists, blinded to each other, extract data from the same study. Intelligent software compares each data field for matches (or mismatches). Where there is a mismatch, a senior scientist reconciles the data mismatch. This methodology is used to thoroughly profile the differences in efficacy and QOL/ADL outcomes among leading pharmacologic and non-pharmacologic treatments to identify the complete domain of AD literature, to extract information on intervention, efficacy, and cohort-level evidence available, and to elucidate the great variation in therapy effect. A total of 795 clinical studies reporting AD interventions and outcome data were located. Of those, 280 and 84 publications were identified that investigated drug and non-pharmacologic treatments, respectively, and were included in the analysis. Overall, no significant reduction in cognitive decline or improvement in QOL/ADL scores was demonstrated with either pharmacologic (MSI-E = 0.17±7.41) or non-pharmacologic (MSI-E = -0.49±2.33) treatments. While acetylcholinesterase inhibitors showed the most overall cognitive benefit (MSI-E = 0.56±7.05), the class was also associated with significant reduction in ADL/QOL (MSI-E = -1.13±11.92) and the greatest variability in effect. Within non-pharmacologic treatments, integrative therapies showed the poorest efficacy (MSI-E = -1.77±3.73) but suggested conserved ADL/QOL (MSI-E = 0.01±2.76). The MedAware Systems, Inc. literature database and meta-analytic methodology readily profiles the diversity, poor efficacy, and the corresponding QOL effect of leading drug and non-pharmacologic AD treatments. The roles of publication-, treatment-, and patient-level factors in reported safety and efficacy profiles warrant further investigation .

A NOVEL META-ANALYTIC APPROACH WITH APPLICATIONS TO ALZHEIMER’S DISEASE RESEARCH

Quantitative literature review has evolved from the time of Glass’ (1976) publication, a methodology he called “meta-analysis,” and Tran (1985) published the first meta-analysis in a medical journal (JAMA). Glass advocated for quantitative reviews to include all the scientific evidence. Since then, meta-analyses have, as a priori decisions, excluded relevant evidence. Many analyzed only a handful of trials (Tran's 1985 publication included 95 trials). Excluding relevant evidence does not advance medical science. Ease of access and volume of data available from keyword searches (e.g., PubMed) require a system to enable investigators to comprehensively review, extract, and aggregate all the evidence from medical literature. “Systematic literature review,” followed by analysis of extracted data paints a myopic view of the evidence. Keyword-based searches miss much of the literature. To address this quandary, MedAware Systems, Inc. has developed a process where data extraction is rapid and nearly 100% accurate. Two scientists, blinded to each other, extract data from the same study. Intelligent software guides the initial extraction comparing each data field for matches. For mismatches, a senior scientist reviews and reconciles the data. The database is built and maintained using a process that continuously identifies and downloads the available body of published and unpublished clinical trials literature. Datasets derived from this database support any topic, providing complete coverage of patient, treatment, and outcome domains. A subset of Alzheimer's disease (AD) literature was reviewed to determine whether the literature supports a differential effect of pharmacologic and non-pharmacologic treatments for AD. 795 clinical studies reporting AD interventions and outcomes were processed. 280 and 84 publications investigated pharmacologic and non-pharmacologic treatments, respectively. Overall, analysis showed no significant reduction in cognitive decline or improvement in QOL/ADL scores with either pharmacologic or non-pharmacologic treatments (Ivashchenko 2018). AD literature is vast and difficult to interpret. This integrated process reviewed and analyzed studies in a timely and efficient manner, providing results that traditional approaches cannot duplicate. MedAware Systems’ literature database and meta-analytic methodology readily profiled and demonstrated the diversity, poor efficacy, and ADL/QOL effects of leading pharmacologic and non-pharmacologic AD treatments.

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia

BackgroundWith upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.MethodsWe assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials.ResultsSignificant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures.ConclusionOur findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.

Effects of subjective sleep status on the cognition of the elderly in community

Objective To explore the effects of sleep status on the cognition of the elderly in community, so as to provide evidence for the prevention and reduction of cognitive decline. Methods A total of 192 healthy elderly people from 2 communities in Haidian District of Beijing were selected by convenience sampling method. All the objects were investigated with Mini Mental State Examination (MMSE) , repeatable Battery for the Assessment of Neuropsychological Status (rBANS) , Activities of Daily Living (ADL) and Physical Activity Scale for the Elderly (PASE) after signing the consent form. The influencing factors of the cognition function were analyzed by multiple linear regression. Results Within the 192 healthy elderly, 42 individuals reported having subjective sleep problems, and 150 individuals reporting normal sleep. There was no significant difference in gener, age and education level between the two groups (P>0.05) . In rBANS assessment, the score of list learning of the sleep problem group (19.21±6.06) was lower than that of the normal sleep group (21.69±5.82) , with statistical significance (t=2.42, P=0.02) . However, there was no significant difference between two groups in the other 11 subtests of rBANS, such as story memory and figure copy (P>0.05) . In addition, there were no significant differences in the total score of MMSE, ADL and PASE between the two groups (P>0.05) . Multiple linear regression analysis showed that age, year of education, and sleep disorder had impacts on list learning (P<0.05) . Conclusions The subjective reporting of poor sleep has an adverse effect on the short-term verbal memory in elderly who are in a general healthy situation. Sleep health management and care is a critical issue in the prevention of cognitive decline in elderly people. Key words: Sleep; Aged; Community health services; Cognition

Serum Albumin's Protective Inhibition of Amyloid-β Fiber Formation Is Suppressed by Cholesterol, Fatty Acids and Warfarin

Central to Alzheimer's disease (AD) pathology is the assembly of monomeric amyloid-β peptide (Aβ) into oligomers and fibers. The most abundant protein in the blood plasma and cerebrospinal fluid is human serum albumin. Albumin can bind to Aβ and is capable of inhibiting the fibrillization of Aβ at physiological (μM) concentrations. The ability of albumin to bind Aβ has recently been exploited in a phase II clinical trial, which showed a reduction in cognitive decline in AD patients undergoing albumin–plasma exchange. Here we explore the equilibrium between Aβ monomer, oligomer and fiber in the presence of albumin. Using transmission electron microscopy and thioflavin-T fluorescent dye, we have shown that albumin traps Aβ as oligomers, 9 nm in diameter. We show that albumin-trapped Aβ oligomeric assemblies are not capable of forming ion channels, which suggests a mechanism by which albumin is protective in Aβ-exposed neuronal cells. In vivo albumin binds a variety of endogenous and therapeutic exogenous hydrophobic molecules, including cholesterol, fatty acids and warfarin. We show that these molecules bind to albumin and suppress its ability to inhibit Aβ fiber formation. The interplay between Aβ, albumin and endogenous hydrophobic molecules impacts Aβ assembly; thus, changes in cholesterol and fatty acid levels in vivo may impact Aβ fibrillization, by altering the capacity of albumin to bind Aβ. These observations are particularly intriguing given that high cholesterol or fatty acid diets are well-established risk factors for late-onset AD.

Role of presynaptic calcium stores for neural network dysfunction in Alzheimer's disease.

Role of presynaptic calcium stores for neural network dysfunction in Alzheimer's disease.

Physical Exercise As Stabilizer For Alzheimer'S Disease Cognitive Decline: Current Status.

Introduction: Mental health decline is one of the main responsible factors for augments in health care costs, and diagnosis of Alzheimer’s disease (AD). Some studies stated physical exercise is useful for reduction in cognitive decline and AD. Moreover, a recent review argued that evidence are scarce due to few studies published and lack of configuration information of exercise protocol, such as intensity and duration of exercise, number of sessions and other relevant data, to allow appropriate assessment.Materials and Methods:Here, we discussed the possible confounders or factors responsible for these differences and possible neurophysiological mechanisms.Results:Most studies revealed a possible positive association between physical exercise and cognitive assessments. There are inconsistencies in studies design responsible for varying use of cognitive assessments and different assessments of fitness. However, these studies do not fail to provide evidence about the benefits of exercise, but fail to make it possible because of the lack of dose-response information in AD patients. Physical exercise of moderate intensity should be considered as standard recommendation to reduce cognitive decline, probably due to the improvement in neurodegenerative mechanisms, and the increase in neuroplastic and neuroprotective neurotrophic factors.Conclusion: Therefore, it is suggested that physical exercise is an important neuroprotective modulator, bringing significant control of the disease and amplifying brain functions.

Reduction of Cognitive Decline in Patients with or at High Risk for Diabetes.

The incidence of Alzheimer's disease and related disorders is expected to triple by 2050. People with type 2 diabetes and prediabetes have a higher risk of cognitive dysfunction, including Alzheimer's disease and vascular dementia. Controversy remains about when and how to prevent and treat cognitive dysfunction in people with or at high risk of diabetes. In our review of ongoing clinical trials, we have found that there has been an increase in the number of studies assessing the efficacy of pharmacological and non-pharmacological approaches to prevent or slow down cognitive impairment among people with or at high risk of diabetes. Despite the considerable risk of cognitive impairment in people with diabetes and prediabetes, there is not enough evidence to support a specific treatment to prevent or slow mild cognitive impairment, or progression to Alzheimer's disease or related disorders. Several ongoing trials are attempting to identify the usefulness of several compounds, as well as lifestyle changes including exercise and diet. Direct mechanisms linking diabetes to cognitive decline have not been elucidated.

ELECTRONIC DEVICES FOR COGNITIVE IMPAIRMENT SCREENING: A SYSTEMATIC LITERATURE REVIEW.

The reduction in cognitive decline depends on timely diagnosis. The aim of this systematic review was to analyze the current available information and communication technologies-based instruments for cognitive decline early screening and detection in terms of usability, validity, and reliability. Electronic searches identified 1,785 articles of which thirty-four met the inclusion criteria and were grouped according to their main purpose into test batteries, measures of isolated tasks, behavioral measures, and diagnostic tools. Thirty one instruments were analyzed. Fifty-two percent were personal computer based, 26 percent tablet, 13 percent laptop, and 1 was mobile phone based. The most common input method was touchscreen (48 percent). The instruments were validated with a total of 4,307 participants: 2,146 were healthy older adults (M = 73.59; SD = 5.12), 1,104 had dementia (M = 74.65; SD = 3.98) and 1,057 mild cognitive impairment (M = 74.84; SD = 4.46). Only 6 percent were administered at home, 19 percent reported outcomes about usability, and 22 percent about understandability. The methodological quality of the studies was good, the weakest methodological area being usability. Most of the instruments obtained acceptable values of specificity and sensitivity. It is necessary to create home delivered instruments and to include usability studies in their design. Involvement of people with cognitive decline in all phases of the development process is of great importance to obtain valuable and user-friendly products. It would be advisable for researchers to make an effort to provide cutoff points for their instruments.

Design and Rationale for a Cognitive Outcome Substudy in Ischemic Stroke Patients with High Risk of Cerebral Hemorrhage

Cognitive impairment and dementia are common disabilities after stroke and are associated with increased risks of mortality and recurrent stroke. The prevention of dementia and preserving cognitive function are also important in stroke patients, but its strategy is not established yet. This PICASSO-COG (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage for reducing COGnitive decline) substudy aims to assess the effects of cilostazol and/or probucol on cognitive function. The substudy aims to assess the reduction in cognitive decline of patients treated with cilostazol and/or probucol in the PICASSO trial. Patients will be assessed using the Korean version of mini-mental state examination and Montreal Cognitive Assessment at 4, 7, 10, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mini-mental status examination score, compared between treatment groups, with a modified intention-to-treat population using a restricted maximum likelihood-based mixed effects model repeat measurement. This will allow a within-subject correlation due to repeated cognitive tests as well as a different number of measurements among subjects at baseline and each follow-up period. PICASSO-COG is a novel study for assessing the effect on cognitive function of different antiplatelet regimens and the addition of a nonstatin lipid-lowering agent to the current standard statin therapy in patients who have a recent ischemic lesion and prior intracerebral macro- or microbleeds.

Cognitively Stimulating Leisure Activity and Subsequent Cognitive Function: A SHARE-based Analysis.

The aim of the inquiry was to examine whether cognitively stimulating leisure activity (CSLA) can delay or reduce cognitive decline in late life and whether its effect is moderated by education, age, or activity pattern. Employing secondary analysis of data on respondents aged 65 and older from the 4th and 5th waves of the Survey of Health, Ageing and Retirement in Europe (N = 16,572), the inquiry regressed cognitive function (memory, numeracy, and fluency) at Time 2 on frequency of engagement in CSLA at baseline, controlling for cognitive function scores at baseline and a range of confounders. The study also considered education by CSLA and age by CSLA interactions, as well as the effect of CSLA patterns. CSLA frequency was found to be positively related to subsequent cognitive functioning on all measures, 2 years later. The effect of CSLA on memory and fluency was stronger among those with lower education, whereas the age by CSLA interaction was not significant. Respondents who started CSLA after baseline showed better cognitive functioning at Time 2 than those who did not engage in CSLA at all and those who had engaged in such activity at baseline but stopped. The study documents that CSLAs constitute a potential source for the delay or reduction of cognitive decline, regardless of one's age. As such, practitioners should recognize the value of this medium and encourage its greater use in appropriate settings.

Nutrient intake, nutritional status, and cognitive function with aging.

With the demographic aging of populations worldwide, diseases associated with aging are becoming more prevalent and costly to individuals, families, and healthcare systems. Among aging-related impairments, a decline in cognitive function is of particular concern, as it erodes memory and processing abilities and eventually leads to the need for institutionalized care. Accumulating evidence suggests that nutritional status is a key factor in the loss of cognitive abilities with aging. This is of tremendous importance, as dietary intake is a modifiable risk factor that can be improved to help reduce the burden of cognitive impairment. With respect to nutrients, there is evidence to support the critical role of several B vitamins in particular, but also of vitamin D, antioxidant vitamins (including vitamin E), and omega-3 fatty acids, which are preferentially taken up by brain tissue. On the other hand, high intakes of nutrients that contribute to hypertension, atherosclerosis, and poor glycemic control may have negative effects on cognition through these conditions. Collectively, the evidence suggests that considerable slowing and reduction of cognitive decline may be achieved by following a healthy dietary pattern, which limits intake of added sugars, while maximizing intakes of fish, fruits, vegetables, nuts, and seeds.

Antihypertensive drugs, prevention of cognitive decline and dementia: a systematic review of observational studies, randomized controlled trials and meta-analyses, with discussion of potential mechanisms.

Chronic hypertension, particularly midlife high blood pressure, has been associated with an increased risk for cognitive decline and dementia. In this context, antihypertensive drugs might have a preventive effect, but the association remains poorly understood. The aim of this systematic review was to examine all published findings that investigated this relationship and discuss the mechanisms underlying the potential benefits of antihypertensive medication use. A literature search was conducted using MEDLINE, Embase, and the Cochrane Library for publications from 1990 onwards mentioning hypertension, antihypertensive drugs, cognitive decline, and dementia. A total of 38 relevant publications, corresponding to 18 longitudinal studies, 11 randomized controlled trials, and nine meta-analyses were identified from the 10,251 articles retrieved in the literature search. In total, 1,346,176 subjects were included in these studies; the average age was 74 years. In the seven longitudinal studies assessing the effect of antihypertensive medication on cognitive impairment or cognitive decline, antihypertensive drugs appeared to be beneficial. Of the 11 longitudinal studies that assessed the effect of antihypertensive medication on incidence of dementia, only three did not find a significant protective effect. Antihypertensive medication could decrease the risk of not only vascular dementia but also Alzheimer's disease. Four randomized controlled trials showed a potentially preventive effect of antihypertensive drugs on the incidence of dementia or cognitive decline: SYST-EUR (Systolic Hypertension in Europe Study) I and II, with a 55% reduction in dementia risk (3.3 vs. 7.4 cases per 1,000 patient years; p<0.001); HOPE (Heart Outcomes Prevention Evaluation), with a 41% reduction in cognitive decline associated with stroke (95% confidence interval [CI] 6-63); and PROGRESS (Perindopril Protection against Recurrent Stroke Study), with a 19% reduction in cognitive decline (95% CI 4-32; p=0.01). Meta-analyses have sometimes produced conflicting results, but this may be due to methodological considerations. The lack of homogeneity across study designs, patient populations, exposition, outcomes, and duration of follow-up are the most important methodological limitations that might explain the discrepancies between some of these studies. Antihypertensive drugs, particularly calcium channel blockers and renin-angiotensin system blockers, may be beneficial in preventing cognitive decline and dementia. However, further randomized controlled trials with longer periods of follow-up and cognition as the primary outcome are needed to confirm these findings.