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Cognitive decline

About: Cognitive decline is a research topic. Over the lifetime, 29308 publications have been published within this topic receiving 1174689 citations.


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TL;DR: The hypothesis that treatment with brain-penetrating ACE inhibitors would slow the rate of cognitive decline in mild-to-moderate AD patients with hypertension is tested.
Abstract: There is evidence that certain components of the renin-angiotensin system (RAS) may have a crucial role in learning and memory processes.1,2⇓ Angiotensin-converting enzyme (ACE) is overexpressed in the hippocampus, frontal cortex, and caudate nucleus of patients with Alzheimer disease (AD).1 In an animal model with AD, brain-distributing ACE inhibitors are reported to rescue neuronal damage and improve behavior.2 Furthermore, we have shown that brain-penetrating ACE inhibitors can reduce the incidence of AD in elderly hypertensive patients.3 In the present study, we tested the hypothesis that treatment with brain-penetrating ACE inhibitors3 would slow the rate of cognitive decline in mild-to-moderate AD patients with hypertension. We performed a randomized, prospective, parallel group trial with 1-year exposure to study medications. Participants were recruited from three long-term care facilities in Sendai, Japan. Patients eligible for this study had a diagnosis of mild to moderate AD,4,5⇓ were aged 65 years and older, had Mini-Mental State Examination (MMSE) scores within the range of 13 to 23, showed no evidence of stroke; insulin-dependent diabetes mellitus, or other endocrine disorders, or asthma or obstructive pulmonary disease, and had a blood pressure of higher than 140 mm Hg systolic or 90 mm Hg diastolic. The diagnosis of probable AD was made according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria with no clinical or laboratory evidence of a cause other than AD for dementia.5 Brain MRI was obtained in all participants within 3 months prior to the study enrollment to exclude patients with possible or probable vascular dementia and other neurodegenerative dementias. Patients …

236 citations

Journal ArticleDOI
TL;DR: The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people and the main reported side-effect was mild gastrointestinal problems.
Abstract: BACKGROUND: Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA) may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomized controlled trials. OBJECTIVES: To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people. METHODS: Search: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on - 6 April 2012 using the terms: "omega 3", PUFA, "fatty acids", "fatty acid", fish, linseed, eicosapentaenoic, docosahexaenoic. Selection criteria: Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials. Data collection and analysis: The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) on an intention-to-treat basis, and summarized narratively information on safety and adherence. MAIN RESULTS: Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up. In two studies participants received gel capsules containing either omega-3 PUFA (the intervention) or olive or sunflower oil (placebo) for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies had cognitive health as their primary outcome; one study of cardiovascular disease included cognitive health as an additional outcome. None of the studies examined the effect of omega-3 PUFA on incident dementia. In two studies involving 3221 participants there was no difference between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention); MD-0.07 (95% CI -0.25 to 0.10). In two studies involving 1043 participants, other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies. The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems. Overall, minor adverse events were reported by fewer than 15% of participants, and reports were balanced between intervention groups. Adherence to the intervention was on average over 90% among people who completed the trials. All three studies included in this review are of high methodological quality. AUTHORS' CONCLUSIONS: Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems. Further studies of longer duration are required. Longer-term studies may identify greater change in cognitive function in study participants which may enhance the ability to detect the possible effects of omega-3 PUFA supplementation in preventing cognitive decline in older people.

236 citations

Journal ArticleDOI
TL;DR: IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice and modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/ PS1 mice.
Abstract: Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

236 citations

Journal ArticleDOI
TL;DR: To assess the interactions among three types of pathology (ie, cerebrovascular disease, hippocampal sclerosis [HS], and Alzheimer's disease [AD]), cognitive status, and apolipoprotein E genotype, data are analyzed on mice with hippocampus-based dementia.
Abstract: Cerebrovascular disease (CVD) is an important, but heterogeneous, cause of cognitive impairment and dementia Several subtypes of ischemic vascular dementia (IVD) have been proposed, including multiinfarct dementia, strategic infarct dementia, Binswanger’s syndrome, and subcortical ischemic vascular dementia (SIVD) Recently, SIVD has been defined by the presence of dementia often with prominent dysexecutive rather than amnestic features, combined with hyperintensities in subcortical gray and white matter as visualized by proton density and T2-weighted magnetic resonance imaging (MRI)1,2 (In this article, CVD and sCVD refer to pathological findings, whereas IVD and SIVD refer to clinical diagnoses) Several mechanisms have been postulated whereby subcortical cerebrovascular disease (sCVD) may cause or contribute to progressive cognitive impairment According to the lacunar hypothesis, infarcts that are strategically located in frontal-subcortical loops may lead to abrupt changes in cognition and behavior3 In Binswanger’s syndrome, hypoperfusion and demyelination of the deep white matter are postulated to cause slowly progressive cognitive impairment, gait disturbance, and urinary incontinence4 In most cases of slowly progressive dementia, however, many investigators posit occult Alzheimer’s disease (AD), rather than lacunes, as the predominant cause of dementia5 Mixed or combined contributions have also been proposed, with CVD and AD pathological changes contributing independently to dementia6,7 Further elucidation of the cognitive impact of combined AD and CVD pathology depends on autopsy studies, because histological examination remains the best method for ascertaining the extent and severity of microscopic AD and CVD pathological alterations within the brain A major goal of the Ischemic Vascular Dementia (IVD) program project (PO1-AG12435) is to elucidate how CVD leads to cognitive impairment, either alone or in combination with AD In this research project, individuals with cognitive impairment attributed to SIVD or AD, as well as cognitively normal (CN) elderly subjects, are followed longitudinally to autopsy with repeat neuropsychological testing and structural MRI studies Previous analyses from this project have shown that MR-assessed volumes of the hippocampus and cortical gray matter are stronger predictors of cognitive impairment and cognitive decline than are MR-assessed volumes of white matter hyperintensities and lacunes8–10 The spectrum of pathological changes observed in the first 20 autopsy cases (eg, including frequent cortical microinfarcts and hippocampal sclerosis [HS])11 and the neuropsychological correlates for the first 46 autopsy cases12 have been published previously We now report data from the first 79 consecutive autopsies regarding (1) correlations between clinical diagnosis and pathological findings, and (2) the relative contributions of CVD, AD pathology, and HS to cognitive impairment

236 citations

Journal ArticleDOI
TL;DR: The results demonstrate that, in AD, increased cerebrospinal fluid orexin levels are related to a parallel sleep deterioration, which appears to be associated with cognitive decline.
Abstract: Importance Nocturnal sleep disruption develops in Alzheimer disease (AD) owing to the derangement of the sleep-wake cycle regulation pathways. Orexin contributes to the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness. Objectives To study cerebrospinal fluid levels of orexin in patients with AD, to evaluate the relationship of orexin cerebrospinal fluid levels with the degree of dementia and the cerebrospinal fluid AD biomarkers (tau proteins and β-amyloid 1-42), and to analyze potentially related sleep architecture changes measured by polysomnography. Design, setting, and participants We conducted a case-control study from August 1, 2012, through May 31, 2013. We included 48 drug-naive AD patients referred to the Neurological Clinic of the University Hospital of Rome Tor Vergata. Based on the Mini-Mental State Examination score, 21 patients were included in mild AD group (score, ≥21), whereas 27 were included in the moderate to severe AD group (score, Exposure Laboratory assessment of cerebrospinal fluid levels of orexin, tau proteins, and β-amyloid 1-42 and polysomnographic assessment of sleep variables. Main outcomes and measures Levels of orexin, tau proteins, and β-amyloid 1-42; macrostructural variables of nocturnal sleep (total sleep time, sleep efficiency, sleep onset and rapid eye movement [REM] sleep latencies, non-REM and REM sleep stages, and wakefulness after sleep onset); and Mini-Mental State Examination scores. Results Patients with moderate to severe AD presented with higher mean (SD) orexin levels compared with controls (154.36 [28.16] vs 131.03 [26.55]; P Conclusions and relevance Our results demonstrate that, in AD, increased cerebrospinal fluid orexin levels are related to a parallel sleep deterioration, which appears to be associated with cognitive decline. Therefore, the orexinergic system seems to be dysregulated in AD, and its output and function appear to be overexpressed along the progression of the neurodegenerative process. This overexpression may result from an imbalance of the neurotransmitter networks regulating the wake-sleep cycle toward the orexinergic system promoting wakefulness.

236 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023914
20221,895
20213,389
20202,982
20192,551
20182,022