-
The Lancet. Psychiatry Feb 2020Cognitive symptoms are common, and yet many who seek help for cognitive symptoms neither have, nor go on to develop, dementia. A proportion of these people are likely to...
Cognitive symptoms are common, and yet many who seek help for cognitive symptoms neither have, nor go on to develop, dementia. A proportion of these people are likely to have functional cognitive disorders, a subtype of functional neurological disorders, in which cognitive symptoms are present, associated with distress or disability, but caused by functional alterations rather than degenerative brain disease or another structural lesion. In this Review, we have systematically examined the prevalence and clinical associations of functional cognitive disorders, and related phenotypes, within the wider cognitive disorder literature. Around a quarter of patients presenting to memory clinics received diagnoses that might indicate the presence of functional cognitive disorders, which were associated with affective symptoms, negative self-evaluation, negative illness perceptions, non-progressive symptom trajectories, and linguistic and behavioural differences during clinical interactions. Those with functional cognitive disorder phenotypes are at risk of iatrogenic harm because of misdiagnosis or inaccurate prediction of future decline. Further research is imperative to improve diagnosis and identify effective treatments for functional cognitive disorders, and better understanding these phenotypes will also improve the specificity of diagnoses of prodromal degenerative brain disease.
Topics: Affective Symptoms; Attitude to Health; Cognition Disorders; Humans; Medically Unexplained Symptoms; Memory Disorders
PubMed: 31732482
DOI: 10.1016/S2215-0366(19)30405-5 -
Psychosomatic Medicine Apr 2010To assess the effects of aerobic exercise training on neurocognitive performance. Although the effects of exercise on neurocognition have been the subject of several... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the effects of aerobic exercise training on neurocognitive performance. Although the effects of exercise on neurocognition have been the subject of several previous reviews and meta-analyses, they have been hampered by methodological shortcomings and are now outdated as a result of the recent publication of several large-scale, randomized, controlled trials (RCTs).
METHODS
We conducted a systematic literature review of RCTs examining the association between aerobic exercise training on neurocognitive performance between January 1966 and July 2009. Suitable studies were selected for inclusion according to the following criteria: randomized treatment allocation; mean age > or =18 years of age; duration of treatment >1 month; incorporated aerobic exercise components; supervised exercise training; the presence of a nonaerobic-exercise control group; and sufficient information to derive effect size data.
RESULTS
Twenty-nine studies met inclusion criteria and were included in our analyses, representing data from 2049 participants and 234 effect sizes. Individuals randomly assigned to receive aerobic exercise training demonstrated modest improvements in attention and processing speed (g = 0.158; 95% confidence interval [CI]; 0.055-0.260; p = .003), executive function (g = 0.123; 95% CI, 0.021-0.225; p = .018), and memory (g = 0.128; 95% CI, 0.015-0.241; p = .026).
CONCLUSIONS
Aerobic exercise training is associated with modest improvements in attention and processing speed, executive function, and memory, although the effects of exercise on working memory are less consistent. Rigorous RCTs are needed with larger samples, appropriate controls, and longer follow-up periods.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Attention; Cognition; Cognition Disorders; Executive Function; Exercise; Exercise Therapy; Humans; Memory; Middle Aged; Neuropsychological Tests; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 20223924
DOI: 10.1097/PSY.0b013e3181d14633 -
Frontiers in Pharmacology 2020Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a... (Review)
Review
Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function. Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies that examined the effects of CBD on brain function of healthy volunteers and individuals diagnosed with a psychiatric disorder, comprising both the effects of CBD alone as well as in direct comparison to those induced by ∆9-tetrahydrocannabinol (THC), the main psychoactive component of . One-ninety four studies were identified, of which 17 met inclusion criteria. All studies investigated the acute effects of CBD on brain function during resting state or in the context of cognitive tasks. In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC. Furthermore, CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms, such as emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital). In individuals at clinical high risk for psychosis and patients with established psychosis, acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance. CBD modulated resting limbic activity in subjects with anxiety and metabolite levels in patients with autism spectrum disorders. Neuroimaging studies have shown that acute CBD induces significant alterations in brain activity and connectivity patterns during resting state and performance of cognitive tasks in both healthy volunteers and patients with a psychiatric disorder. This included modulation of functional networks relevant for psychiatric disorders, possibly reflecting CBD's therapeutic effects. Future studies should consider replication of findings and enlarge the inclusion of psychiatric patients, combining longer-term CBD treatment with neuroimaging assessments.
PubMed: 33551817
DOI: 10.3389/fphar.2020.618184 -
International Journal of Molecular... Jan 2023Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease typically characterized by memory loss, personality changes, and a decline in... (Review)
Review
Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease typically characterized by memory loss, personality changes, and a decline in overall cognitive function. Usually manifesting in individuals over the age of 60, this is the most prevalent type of dementia and remains the fifth leading cause of death among Americans aged 65 and older. While the development of effective treatment and prevention for AD is a major healthcare goal, unfortunately, therapeutic approaches to date have yet to find a treatment plan that produces long-term cognitive improvement. Drugs that may be able to slow down the progression rate of AD are being introduced to the market; however, there has been no previous solution for preventing or reversing the disease-associated cognitive decline. Recent studies have identified several factors that contribute to the progression and severity of the disease: diet, lifestyle, stress, sleep, nutrient deficiencies, mental health, socialization, and toxins. Thus, increasing evidence supports dietary and other lifestyle changes as potentially effective ways to prevent, slow, or reverse AD progression. Studies also have demonstrated that a personalized, multi-therapeutic approach is needed to improve metabolic abnormalities and AD-associated cognitive decline. These studies suggest the effects of abnormalities, such as insulin resistance, chronic inflammation, hypovitaminosis D, hormonal deficiencies, and hyperhomocysteinemia, in the AD process. Therefore a personalized, multi-therapeutic program based on an individual's genetics and biochemistry may be preferable over a single-drug/mono-therapeutic approach. This article reviews these multi-therapeutic strategies that identify and attenuate all the risk factors specific to each affected individual. This article systematically reviews studies that have incorporated multiple strategies that target numerous factors simultaneously to reverse or treat cognitive decline. We included high-quality clinical trials and observational studies that focused on the cognitive effects of programs comprising lifestyle, physical, and mental activity, as well as nutritional aspects. Articles from PubMed Central, Scopus, and Google Scholar databases were collected, and abstracts were reviewed for relevance to the subject matter. Epidemiological, pathological, toxicological, genetic, and biochemical studies have all concluded that AD represents a complex network insufficiency. The research studies explored in this manuscript confirm the need for a multifactorial approach to target the various risk factors of AD. A single-drug approach may delay the progression of memory loss but, to date, has not prevented or reversed it. Diet, physical activity, sleep, stress, and environment all contribute to the progression of the disease, and, therefore, a multi-factorial optimization of network support and function offers a rational therapeutic strategy. Thus, a multi-therapeutic program that simultaneously targets multiple factors underlying the AD network may be more effective than a mono-therapeutic approach.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; Cognitive Dysfunction; Cognition; Memory Disorders
PubMed: 36675177
DOI: 10.3390/ijms24021659 -
Journal of Parkinson's Disease 2018Cognitive dysfunction is one of the most prevalent non-motor symptoms in Parkinson's disease (PD), often experienced as more debilitating for patients and caregivers...
BACKGROUND
Cognitive dysfunction is one of the most prevalent non-motor symptoms in Parkinson's disease (PD), often experienced as more debilitating for patients and caregivers than motor problems. Therefore, a deeper understanding of the course of cognitive decline and the identification of valid progression markers for Parkinson's disease dementia (PDD) is essential.
OBJECTIVE
This systematic review summarizes the current state of knowledge on cognitive decline over time by reporting effect sizes of cognitive changes in neuropsychological tests.
METHODS
1368 studies were identified by a PubMed database search and 25 studies by additionally scanning previous literature. After screening all records, including 69 full-text article reviews, 12 longitudinal studies on the progression of cognitive decline in PD met our criteria (e.g., sample size ≥50 patients).
RESULTS
Only a few studies monitored cognitive decline over a longer period (>4 years). Most studies focused on the evaluation of change in global cognitive state by use of the Mini-Mental State Examination, whereas the use of neuropsychological tests was highly heterogenic among studies. Only one study evaluated patients' cognitive performance in all specified domains (executive function, attention & working memory, memory, language, and visual-spatial function) allowing for diagnosis of cognitive impairment according to consensus guidelines. Medium to strong effect sizes could only be observed in studies with follow-up intervals of four years or longer.
CONCLUSIONS
The results emphasize the need for the assessment of larger PD cohorts over longer periods of follow-up with a comprehensive neuropsychological battery.
Topics: Attention; Cognition; Cognition Disorders; Disease Progression; Executive Function; Humans; Language; Memory, Short-Term; Neuropsychological Tests; Parkinson Disease
PubMed: 29914040
DOI: 10.3233/JPD-181306 -
Medicina (Kaunas, Lithuania) Dec 2021: Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as... (Meta-Analysis)
Meta-Analysis Review
: Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as facial flushing, nasal stuffiness, and sweating. Their major treatment methods include medication and cognitive behavioral therapy (CBT). CBT has been used for pain treatment and various psychogenic neurological diseases by reducing pain, disability, and emotional disorders caused by symptoms of mental illness and improving the understanding of mental health. This study aimed to evaluate the effectiveness and safety of CBT in treating migraines. : Seven electronic databases were searched from the date of inception to December 2020. Randomized controlled studies (RCTs) using CBT as an intervention for migraine were included. The primary outcome of this study was to determine the frequency of migraines and the intensity of migraines on Visual Analog Scale (VAS), the frequency of drug use, Migraine Disability Assessment (MIDAS), and Headache Impact Test (HIT-6) index. The two authors independently conducted the data extraction and quality assessment of the included RCTs, and conducted meta-analysis with RevMan V.5.4. : Among the 373 studies, 11 RCTs were included in this systematic review. Seven out of the 11 RCTs were conducted in the USA, and four were conducted in the UK, Germany, Iran, and Italy, respectively. Headache frequency and MIDAS scores were statistically significant reduced. In the subgroup analysis, headache strength was significantly reduced. Two of the included studies reported adverse effects, including worsening of migraine intensity and frequency, respiratory symptoms, and vivid memory of a traumatic event. : CBT for migraine effectively reduced headache frequency and MIDAS score in meta-analysis and headache intensity subgroup analysis, with few adverse events. Additional RCTs with CBT for migraine headaches are needed for a more accurate analysis.
Topics: Cognitive Behavioral Therapy; Disability Evaluation; Headache; Humans; Migraine Disorders; Pain Measurement
PubMed: 35056352
DOI: 10.3390/medicina58010044 -
Neuroscience and Biobehavioral Reviews Aug 2021Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical... (Meta-Analysis)
Meta-Analysis Review
Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer's disease and insomnia: A systematic review and meta-analysis of randomized controlled trials.
Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical trials, whether melatonin may also enhance cognitive function remains elusive. This study examined cognitive outcomes from randomized trials of melatonin treatment for Alzheimer's disease (AD), insomnia, and healthy-subjects. Twenty-two studies met the inclusion criteria (AD = 9, insomnia = 2, healthy-subjects = 11). AD patients receiving >12 weeks of melatonin treatment improved mini-mental state examination (MMSE) score [MD: 1.82 (1.01; 2.63) p < 0.0001]. Importantly, melatonin significantly improved MMSE score in mild stage of AD [MD: 1.89 (0.96; 2.82) p < 0.0001]. In healthy-subjects, although daytime melatonin treatment notably decreased in accuracy by correct responses [SMD: -0.74 (-1.03; -0.45) p < 0.00001], the reaction-time score on different stimuli (p = 0.37) did not increased. Additionally, by pooling of short-term, spatial, and visual memory scores, melatonin did not reduce memory function (p = 0.08). Meta-analysis of MMSE score suggested that melatonin is effective in treatment for mild stage of AD. Additionally, we propose that melatonin may be preferable to traditional hypnotics in management of insomnia.
Topics: Adult; Alzheimer Disease; Cognition Disorders; Humans; Melatonin; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 33957167
DOI: 10.1016/j.neubiorev.2021.04.034 -
PloS One 2023Alzheimer's disease (AD) is a neurodegenerative disorder that causes gradual memory loss. AD and its prodromal stage of mild cognitive impairment (MCI) are marked by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a neurodegenerative disorder that causes gradual memory loss. AD and its prodromal stage of mild cognitive impairment (MCI) are marked by significant gut microbiome perturbations, also known as gut dysbiosis. However, the direction and extent of gut dysbiosis have not been elucidated. Therefore, we performed a meta-analysis and systematic review of 16S gut microbiome studies to gain insights into gut dysbiosis in AD and MCI.
METHODS
We searched MEDLINE, Scopus, EMBASE, EBSCO, and Cochrane for AD gut microbiome studies published between Jan 1, 2010 and Mar 31, 2022. This study has two outcomes: primary and secondary. The primary outcomes explored the changes in α-diversity and relative abundance of microbial taxa, which were analyzed using a variance-weighted random-effects model. The secondary outcomes focused on qualitatively summarized β-diversity ordination and linear discriminant analysis effect sizes. The risk of bias was assessed using a methodology appropriate for the included case-control studies. The geographic cohorts' heterogeneity was examined using subgroup meta-analyses if sufficient studies reported the outcome. The study protocol has been registered with PROSPERO (CRD42022328141).
FINDINGS
Seventeen studies with 679 AD and MCI patients and 632 controls were identified and analyzed. The cohort is 61.9% female with a mean age of 71.3±6.9 years. The meta-analysis shows an overall decrease in species richness in the AD gut microbiome. However, the phylum Bacteroides is consistently higher in US cohorts (standardised mean difference [SMD] 0.75, 95% confidence interval [CI] 0.37 to 1.13, p < 0.01) and lower in Chinese cohorts (SMD -0.79, 95% CI -1.32 to -0.25, p < 0.01). Moreover, the Phascolarctobacterium genus is shown to increase significantly, but only during the MCI stage.
DISCUSSION
Notwithstanding possible confounding from polypharmacy, our findings show the relevance of diet and lifestyle in AD pathophysiology. Our study presents evidence for region-specific changes in abundance of Bacteroides, a major constituent of the microbiome. Moreover, the increase in Phascolarctobacterium and the decrease in Bacteroides in MCI subjects shows that gut microbiome dysbiosis is initiated in the prodromal stage. Therefore, studies of the gut microbiome can facilitate early diagnosis and intervention in Alzheimer's disease and perhaps other neurodegenerative disorders.
Topics: Humans; Female; Middle Aged; Aged; Male; Alzheimer Disease; Gastrointestinal Microbiome; Dysbiosis; Prodromal Symptoms; Bacteroides; Cognitive Dysfunction
PubMed: 37224131
DOI: 10.1371/journal.pone.0285346 -
Nutrients Feb 2022Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity.... (Review)
Review
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. ADHD impairments arise from irregularities primarily in dopamine (DA) and norepinephrine (NE) circuits within the prefrontal cortex. Due to ADHD medication's controversial side effects and high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caffeine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evidence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal studies is lacking. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to 1 September 2021. Caffeine treatment increases attention and improves learning, memory, and olfactory discrimination without altering blood pressure and body weight. These results are supported at the neuronal/molecular level. Nonetheless, the role of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that the cognitive effects of caffeine found in animal models could be translated to human ADHD, particularly during adolescence.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Caffeine; Disease Models, Animal; Dopamine; Humans; Impulsive Behavior
PubMed: 35215389
DOI: 10.3390/nu14040739 -
International Journal of Molecular... Feb 2023Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for more than half of all dementia cases in the elderly. Interestingly, the clinical... (Review)
Review
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for more than half of all dementia cases in the elderly. Interestingly, the clinical manifestations of AD disproportionately affect women, comprising two thirds of all AD cases. Although the underlying mechanisms for these sex differences are not fully elucidated, evidence suggests a link between menopause and a higher risk of developing AD, highlighting the critical role of decreased estrogen levels in AD pathogenesis. The focus of this review is to evaluate clinical and observational studies in women, which have investigated the impact of estrogens on cognition or attempted to answer the prevailing question regarding the use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords "memory", "dementia," "cognition," "Alzheimer's disease", "estrogen", "estradiol", "hormone therapy" and "hormone replacement therapy" and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that contribute to the conflicting findings of HRT in the prevention and treatment of age-related cognitive deficits and AD. The literature suggests that estrogens have a clear role in modulating dementia risk, with reliable evidence showing that HRT can have both a beneficial and a deleterious effect. Importantly, recommendation for the use of HRT should consider the age of initiation and baseline characteristics, such as genotype and cardiovascular health, as well as the dosage, formulation, and duration of treatment until the risk factors that modulate the effects of HRT can be more thoroughly investigated or progress in the development of alternative treatments can be made.
Topics: Female; Humans; Male; Aged; Alzheimer Disease; Estrogen Replacement Therapy; Hormone Replacement Therapy; Estrogens; Estradiol; Risk Factors
PubMed: 36834617
DOI: 10.3390/ijms24043205