Treatment Of Mild Cognitive Impairment Research Articles

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Pilot Study

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer’s disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid β (Aβ) proteins and urine 8-OHdG (8-hydroxy-2′-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-β (1–40) and amyloid-β (1–42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma β-amyloid levels of older adults with memory impairment.

The Association between Physical Activity and Selected Parameters of Psychological Status and Dementia in Older Women.

Physical activity has an unquestionable impact on broadly understood human health. One interesting issue related to this is the importance of movement on mental health and cognitive functioning. Research shows that regular physical activity improves the cognitive functioning of adults and people with mental disorders. Regular physical activity can be an important and powerful protective factor in cognitive impairment and dementia in the elderly, and exercise is an important non-pharmacological treatment for mild cognitive impairment or neurodegenerative diseases. This study aims to present the impact of physical activity on selected cognitive functions in physically active women over 60 years of age. The research was carried out in a group of 110 generally healthy women from the area of western Poland over 60 years of age, who were divided into four groups based on the intensity of their physical activity. A pedometer (sport watch) and a physical activity diary were used to measure physical activity. Body Mass Index was assessed. Selected cognitive functions were assessed using the MMSE test, motor and psychomotor skills were measured, and Luria’s auditory memory test and recall test, a clock drawing test, and a GDS test were performed. There were statistically significant relationships between the level of physical activity and the effectiveness of cognitive processes. These results show that about 5000 steps a day is enough to see a positive effect on the mental health and cognitive functioning of this group of the elderly population. The women had an average BMI of 28.1 ± 4.7. BMI, indicating an overweight condition (over 30 kg/m2), was observed in 31% of women. The results of this study lead the authors to conclude that physical activity positively influences cognitive function and can be recommended for all seniors who do not have other serious comorbidities that would prevent them from playing sports.

TACS as a promising therapeutic option for improving cognitive function in mild cognitive impairment: A direct comparison between tACS and tDCS

Neuromodulation has gained attention as a potential non-pharmacological intervention for mild cognitive impairment (MCI). However, no studies have directly compared the effects of transcranial alternating current stimulation (tACS) with transcranial direct current stimulation (tDCS) on MCI patients. We aimed to identify the more promising and efficient therapeutic option between tACS and tDCS for cognitive enhancement in MCI patients. We compared the effects of gamma-tACS with tDCS on cognitive function and electroencephalography (EEG) in MCI patients. In this sham-controlled, double-blinded, repeated-measures study with the order of the stimulation counterbalanced across patients (n = 20), both gamma-tACS (40 H z) and tDCS were administered at the same intensity (2 mA) in the dorsolateral prefrontal cortex for 30 min. Cognitive tests (Stroop and Trail-Making-Test [TMT]) and EEG were performed before and after single-session stimulation. Gamma-tACS improved the Stroop-color in comparison with tDCS (p = .044) and sham (p = .010) and enhanced the TMT-B in comparison with sham (p = .021). However, tDCS was not significantly different from sham in changes of any cognitive test scores. In EEG analysis, gamma-tACS increased beta activity in comparison with sham and tDCS, whereas tDCS decreased delta and theta activity in comparison with sham. Gamma-tACS also increased beta 2 source activity in the anterior cingulate, compared to sham. The cognitive benefits of tACS in MCI patients appeared superior to those of tDCS. tACS facilitated cognitive function by increasing beta activity, while tDCS delayed the progression of MCI symptoms by decreasing slow-frequency activity. Thus, tACS could be used as a new therapeutic option for MCI.

Mind-Body Exercise Modulates Locus Coeruleus and Ventral Tegmental Area Functional Connectivity in Individuals With Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is a common global health problem. Recently, the potential of mind-body intervention for MCI has drawn the interest of investigators. This study aims to comparatively explore the modulation effect of Baduanjin, a popular mind-body exercise, and physical exercise on the cognitive function, as well as the norepinephrine and dopamine systems using the resting state functional connectivity (rsFC) method in patients with MCI. 69 patients were randomized to the Baduanjin, brisk walking, or healthy education control group for 6 months. The Montreal Cognitive Assessment (MoCA) and magnetic resonance imaging (MRI) scans were applied at baseline and at the end of the experiment. Results showed that (1) compared to the brisk walking, the Baduanjin significantly increased MoCA scores; (2) Baduanjin significantly increased the right locus coeruleus (LC) and left ventral tegmental area (VTA) rsFC with the right insula and right amygdala compared to that of the control group; and the right anterior cingulate cortex (ACC) compared to that of the brisk walking group; (3) the increased right LC-right insula rsFC and right LC-right ACC rsFC were significantly associated with the corresponding MoCA score after 6-months of intervention; (4) both exercise groups experienced an increased effective connectivity from the right ACC to the left VTA compared to the control group; and (5) Baduanjin group experienced an increase in gray matter volume in the right ACC compared to the control group. Our results suggest that Baduanjin can significantly modulate intrinsic functional connectivity and the influence of the norepinephrine (LC) and dopamine (VTA) systems. These findings may shed light on the mechanisms of mind-body intervention and aid the development of new treatments for MCI.

Effect of organophosphate pesticides poisoning on cognitive impairment

It has been suggested that organophosphate pesticides can cause cognitive impairment, most of which are presented as mild cognitive impairment such as decreased attention or vigilance, reduced information processing speed and memory impairment. An early diagnosis and timely intervention in mild cognitive impairment, which may provide a better prognosis. Mild cognitive impairment in clinical work can be easily ignored for a long time. However, it have a particularly impact on patients' life and work, and even progress to irreversible neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Therefore, clinicians should raise the cognition of organophosphate pesticides poisoning in patients with cognitive impairment, especially for patients with mild cognitive impairment, and the significance of early detection and diagnosis of the disease is particularly important.

Acupuncture and Moxibustion Treatment of Mild Cognitive Impairment Based on Data Mining

Acupuncture and moxibustion therapy, as a traditional medical treatment method of the motherland, is widely used in the treatment of mild cognitive dysfunction, with remarkable curative effect, and is increasingly recognized by the medical community. However, so far, there is no acupuncture prescription and acupoint usage rules for acupuncture treatment of mild cognitive impairment. Therefore, it is of great significance to collect, organize and data mining related data in order to summarize the relationship between acupuncture points and mild cognitive dysfunction, and to provide references for clinical treatment. This article standardizes the acupuncture points in the database. This paper uses Excel and SPS software to carry out frequency analysis, cluster analysis and association rules, and draws the rules of acupoints, meridians, positions, frequency of specific acupoints, clustering of acupoints and compatibility. In this paper, the number of cases in the treatment group and the control group, the main acupoints and matching points of the acupuncture prescription, the treatment methods, the efficacy evaluation indicators, and the total effective rate of the treatment group and the control group are extracted into the Excel table to form a mild cognition of acupuncture treatment Prescription database for dysfunction. This article studies the rules and characteristics of acupuncture points derived from data mining, takes the general rules and characteristics of clinical acupuncture and moxibustion treatment as a reference for clinical acupuncture and moxibustion, and verifies it with the results obtained. The experimental results show that in the analysis of association rules, taking Baihui and Shenting as examples, the support degree indicates that the probability that the two acupoints appear in the 126 heads at the same time is 51.83%, and the confidence and support for the occurrence of Baihui and Shenting are relatively high. High, it is considered to be a common compatible point pair for acupuncture treatment of mild cognitive dysfunction.

The Efficacy of Cognitive-Communicative Intervention in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

Mild cognitive impairment (MCI) is the sign of dementia, and is critical for prediction and preventing its progressions. This study aimed to review literature on cognitive communication intervention of MCI patients systematically, and propose the evidence-based data, including their effect sizes using a meta-analysis method. Thirty-eight researches published since 2012, meeting the inclusion and exclusion criteria, were entered into this analysis. They were analyzed in qualitative aspects, and their effect sizes were calculated in a level of mean and each domain. Outcome measures included the domains of 10 cognitions and 4 communications. The main findings were as follows. Firstly, the general target population for studies was MCI over the age of 50, and intervention programs were designed diversely in a session or mode. Secondly, several domains, including attention, memory, and executive function held a large portion of the intervention programs. Thirdly, the average effect size of interventions was large. Lastly, processing speed and word fluency were very effective and significant among domains in the results of treatment. Current study provides evidence-based information to support cognitive-communication intervention for individuals with MCI. These results also can contribute to diversify intervention approaches and verify their efficacies. Given this, it is possible to facilitate the cognitive-communication intervention for MCI in clinical settings.

Acutil® in Mild Cognitive Impairment or Early Dementia: An Exploratory Observational Pilot Study

Background: With no approved treatment for mild cognitive impairment (MCI), attention increasingly turns to qualified food supplements. Objective: To conduct a 12-month rater-blinded exploratory outpatient trial with Acutil®, a supplement consisting of ω-3 polyunsaturated fatty acids, Ginkgo biloba extract, and vitamins, in 50 persons with amnestic MCI or mild to moderate Alzheimer or mixed-type dementia. Methods: The used cognitive tools were the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog), the Mini-Mental State Exam (MMSE), and Controlled Oral Word Association Test (COWAT). Patients were randomized in the ratio of 40:10 to additional Acutil® or no additional supplementation; all continued on their existing medications during the entire study. Results: Only the COWAT produced a clear positive signal in the Acutil® group between individual baseline and study endpoint, but the between-group comparison was not statistically significant. The MMSE score remained stable in the Acutil® group while deteriorating in the control group; post hoc examination suggests that the Acutil® group might have contained responders. The ADAS-Cog and Clinical Dementia Rating (CDR) scores showed marginal deterioration in both groups. Conclusions: We tentatively interpret our results as potentially indicating positive effects of Acutil® on verbal fluency and some aspects of executive function, with an onset after 6 months of continuous treatment. However, much larger and double-blinded studies will be required to make firm statements.

Mindfulness intervention for mild cognitive impairment led to attention-related improvements and neuroplastic changes: Results from a 9-month randomized control trial

Mindfulness-based interventions can enhance cognitive abilities among older adults, thereby effectively delaying cognitive decline. These cognitive enhancements are theorized to accompany neuroplastic changes in the brain. However, this mindfulness-associated neuroplasticity has yet to be documented adequately. A randomized controlled trial was carried out among participants with mild cognitive impairment (MCI) to examine the effects of a mindfulness-based intervention on various cognitive outcomes and cortical thickness (CT) in the context of age-related cognitive impairment. Participants were assigned to a mindfulness awareness program (MAP)(n = 27) and an active control condition — health education program (n = 27). In both, they attended weekly sessions for three months and subsequently, monthly sessions for six months. Cognitive assessments and structural scans were carried out across three time-points. Whole brain analyses on CT were carried out and were supplemented with region of interest-based analyses. ROI values and cognitive outcomes were analyzed with mixed MANOVAs and followed up with univariate ANOVAs. Nine-month MAP-associated gains in working memory span and divided attention, along with an increased CT in the right frontal pole and decreased CT in the left anterior cingulate were observed. Three-month MAP-associated CT increase was observed in the left inferior temporal gyrus but did not sustain thereafter. MAP led to significant cognitive gains and various CT changes. Most of these neurobehavioral changes, may require sustained effort across nine months, albeit at a reduced intensity. MAP can remediate certain cognitive impairments and engender neuroplastic effects even among those with MCI.

The improvement of cognitive deficits after whole-body cryotherapy - A randomised controlled trial.

Whole-body cryotherapy (WBC) - a repetitive, short-term exposure to extremely low temperatures - may become an effective early intervention for mild cognitive impairment (MCI). It is a heterogeneous group of symptoms associated with cognitive dysfunction which is estimated to transform into dementia in 50% cases. The prospective randomised double-blind sham-controlled study aimed to determine the efficacy of WBC on cognitive functioning and biological mechanisms. The study was registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001627145). Participants with MCI (n=62; (20<MoCA>26) were randomly allocated to cryogenic temperatures (-110°C till -160°C) (EG, n=33) or placebo-controlled group (CG, n=29). Cognitive functions were measured at baseline (T1), after the 10th WBC session (T2) and after 2week-break (T3) with DemTect, SLUMS and Test Your Memory (TYM). Secondary outcome measures included quality of life (WHOQoL-BREF), self-reported well-being (VAS) and depressive symptoms (GDS). Whole blood samples (10ml) were collected at T1 and T2 to evaluate levels of cytokines, neurotrophins, NO and biochemical parameters CRP total cholesterol, prolactin). There were significant differences between groups measured at T2 in immediate recall (DemTect) and in orientation (TYM) in favour of WBC group. Improvement in mood was detected in self-reported depressive symptoms level (WHOQoL-26; T2 p=0.04; VAS mood T2 p=0.02; T3 p=0.07). The significant reduction of BDNF level was observed (p<0.05). WBC may increase the performance of cognitive functions. It seems promising to combine WBC with existing behavioural and cognitive trainings in the future studies investigating early interventions methods in MCI.

Impact of cognitive intervention on cognitive symptoms and quality of life in idiopathic Parkinson's disease: a randomized and controlled study.

ABSTRACT.Pharmacological treatments for mild cognitive impairment (MCI), are lacking, and alternative approaches have been implemented, including cognitive training (CT).Objective:To determine the impact of CT on cognitive and quality of life measures in patients with Parkinson’s disease (PD) who were seen a hospital neurorehabilitation program.Methods:Thirty-nine individuals with MCI-PD, according to the Movement Disorder Society, were randomly distributed into two groups: experimental and control group, matched for demographic and clinical characteristics. Both groups were assessed for cognition and quality of life at the beginning of the study and at the end of the intervention protocol. The following instruments were used to assess cognition and quality of life: Addenbrooke’s Cognitive Examination III, Digit Span, Trail Making Test (TMT, A and B) and Parkinson disease quality of life questionnaire. The experimental group (EG) engaged in CT, whereas the control group (CG) underwent activities of the general rehabilitation program.Results:No baseline evaluation differences were found. Intergroup analysis showed differences in measures, such as total score (1.977, p=0.0480) and visuospatial domain (-2.636, p=0.0084) of the ACE-III, with the EG performing better, in addition to better performance in TMT-B mistakes (-1.928, p=0.0439). Intragroup analysis revealed that the EG showed significant improvement in almost all the cognitive variables, well as in self-reported quality of life (total score and mobility, activities of daily living, body discomfort dimensions).Conclusions:Engagement in cognitive activities was associated with better cognitive abilities in PD-MCI. Future studies should consider the long-term effect of this type of intervention and impact on functional activities.

Systematic Evaluation of the Efficacy of Integrated Traditional Chinese and Western Medicine in Treating Mild Cognitive Impairment

Objective: To explore the effectiveness and safety of integrated traditional Chinese and western medicine in the treatment of MCI patients. Methods: Search three English databases, four Chinese databases, and assess the risk of bias according to Cochrane tools. Statistics will be used for heterogeneity assessment, sensitivity analysis, data synthesis, funnel chart generation and subgroup analysis. If a sufficiently uniform study is found, a meta-analysis will be performed and any differences will be described in groups. Results: A total of 15 studies were included, 11 studies treated MMSE as an outcome indicator, 7 studies used MoCA as an outcome indicator, 6 studies reported overall effectiveness, 3 studies used ADL as an outcome indicator, and 2 studies reported blood The data of markers and the results of 15 studies are beneficial to the traditional Chinese medicine combined with western medicine group. Conclusion: The conclusion shows that the treatment of mild cognitive impairment with integrated traditional Chinese and western medicine is superior to the single use of traditional Chinese medicine or western medicine in improving MMSE, MoCA, ADL, total effective rate score and reducing blood markers Aβ and IT-6, and the incidence of adverse reactions Lower, higher safety, for clinical reference. However, there are flaws in the research methodology, which need to be confirmed by more high-quality literature.

Potential Neuroregenerative and Neuroprotective Effects of Uridine/Choline-Enriched Multinutrient Dietary Intervention for Mild Cognitive Impairment: A Narrative Review.

In mild cognitive impairment (MCI) due to Alzheimer disease (AD), also known as prodromal AD, there is evidence for a pathologic shortage of uridine, choline, and docosahexaenoic acid [DHA]), which are key nutrients needed by the brain. Preclinical and clinical evidence shows the importance of nutrient bioavailability to support the development and maintenance of brain structure and function in MCI and AD. Availability of key nutrients is limited in MCI, creating a distinct nutritional need for uridine, choline, and DHA. Evidence suggests that metabolic derangements associated with ageing and disease-related pathology can affect the body’s ability to generate and utilize nutrients. This is reflected in lower levels of nutrients measured in the plasma and brains of individuals with MCI and AD dementia, and progressive loss of cognitive performance. The uridine shortage cannot be corrected by normal diet, making uridine a conditionally essential nutrient in affected individuals. It is also challenging to correct the choline shortfall through diet alone, because brain uptake from the plasma significantly decreases with ageing. There is no strong evidence to support the use of single-agent supplements in the management of MCI due to AD. As uridine and choline work synergistically with DHA to increase phosphatidylcholine formation, there is a compelling rationale to combine these nutrients. A multinutrient enriched with uridine, choline, and DHA developed to support brain function has been evaluated in randomized controlled trials covering a spectrum of dementia from MCI to moderate AD. A randomized controlled trial in subjects with prodromal AD showed that multinutrient intervention slowed brain atrophy and improved some measures of cognition. Based on the available clinical evidence, nutritional intervention should be considered as a part of the approach to the management of individuals with MCI due to AD, including adherence to a healthy, balanced diet, and consideration of evidence-based multinutrient supplements.

Pharmacological and non-pharmacological interventions to enhance sleep in mild cognitive impairment and mild Alzheimer's disease: A systematic review.

Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy – Insomnia (CBT‐I), A Multi‐Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT‐I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co‐existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.

Effect of polyphenol treatment for mild cognitive impairment (MCI) and diabetes

AbstractBackgroundAs the prevalence of Alzheimer’s disease (AD) continues to rise, alternative approaches are sought to have a greater understanding of this neurological disease. One approach of interest would be to identify individuals who are at risk of Alzheimer’s disease (AD) and determine the efficacy of a selected therapeutic. Persons with Mild Cognitive Impairment (MCI) are at risk of incident dementia, and being coupled with deficits in short‐term recall, significantly increases their risk of incident AD. In addition, having risk factors of the metabolic syndrome, such as prediabetes, has also been found to augment the risk of incident cognitive impairment. This is further strengthened by evidence showing neurons in AD brains being insulin resistant. Previous animal studies have found that a nutraceutical containing grape seed polyphenol extract (GSPE) and resveratrol to be associated with improved cognition and lowering brain amyloid and tau burden. The current clinical study is being taken as a first step to investigate the safety and tolerability of GSPE and resveratrol in patients who have Mild Cognitive Impairment (MCI) and diabetes. In addition, this study will also quantify the bioavailability of selected polyphenols and their metabolites, and determine if any changes are seen between the treatment and placebo group at the end of the study in regards to cognitive test scores, and CSF content of tau/β‐amyloid 42.MethodParticipants were entered into a 4 month double‐blinded study and given either a placebo, or a mixture containing 450 mg of GSPE and 125 mg of resveratrol. Serum samples were taken at baseline, 2 months, and 4 months, whereas CSF samples were taken at the start and end of the study.ResultThe study is still ongoing and additional individuals are enrolling in the study. No adverse events related to GSPE and resveratrol have been observed from the participants to date, and compliance has been good.ConclusionAt the conclusion of this clinical trial, in addition to determining the safety and tolerability of GSPE and resveratrol, a greater understanding will be attained as to the potential association of selected polyphenol metabolites and biomarkers of AD neuropathology in CSF.

Improved brain energetics and cognition after a 6‐month ketogenic intervention in mild cognitive impairment: Final results of the Benefic Trial

AbstractBackgroundKetones can partially substitute for glucose as a brain fuel and may be beneficial for cognition in older people. The objective of the randomized, placebo‐controlled Benefic Trial (NCT02551419) was to assess whether counteracting the brain energy (glucose) deficit with a ketogenic medium chain triglyceride (kMCT) supplement could improve cognitive performance in mild cognitive impairment (MCI).MethodsA cognitive battery was used to screen for MCI and cognitive outcomes after the intervention. Cognitive outcomes pre‐ and post‐intervention were obtained for the active arm (15 g kMCT twice/day in a lactose‐free skim milk emulsion; n=39 completers) and placebo arm (non‐ketogenic vegetable oil of equivalent energy value and formulation as for the kMCT; n=44 completers). Brain ketone and glucose PET were done before and at the end of the 6‐month intervention on a sub‐group of both arms (n=19/group).ResultsSeveral cognitive domains improved post‐intervention in the kMCT group (p≤0.01; ANCOVA; age and education as covariates). Specifically, Trial 1 of the Free and Cued Recall Test showed a +1 word improvement on kMCT (+0.5 Δ Z‐score), correct answers on the Verbal Fluency Test increased by 2 words on kMCT (+0.3 Δ Z‐score) but decreased by 1 word on placebo (‐0.1 Δ Z‐score), correct answers on the Boston Naming Test increased by 1.1 on kMCT only, time taken on the Stroop Colour Naming Test decreased by 1 sec on the kMCT (p=0.09), and errors on the Trail Making Test decreased by 0.9 on kMCT but increased by 0.8 on placebo (p=0.02). Brain ketone uptake increased in the kMCT arm only and directly as the increase in plasma ketones (r = 0.87, p&lt;0.01). Average drop‐out rate on both arms was 31% and, in completers, protocol adherence was 89% over six months.ConclusionsIn MCI, a kMCT supplement had a clinically meaningful effect on some cognitive outcomes directly related to risk of progression toward Alzheimer’s disease, and significantly improved brain energy supply. It is feasible for an MCI population to consume a kMCT supplement daily for six months. Acknowledgements: Financial support was provided by the Alzheimer Association USA, FRQS, Université de Sherbrooke and Nestlé Health Science.

The effect of virtual reality (VR)‐based intervention program on brain and cognition in older adults with mild cognitive impairment (MCI)

AbstractBackgroundGiven the current lack of evidence for intervention and disease‐modifying treatment for Mild cognitive impairment (MCI) and dementia, exploring new interventions is important. VR interventions have increasingly gained popularity in psychotherapy and behavioral therapy, and the potential of VR based interventions to improve cognition are also being explored. However, the evidences regarding its effect on dementia are quite ambiguous. Therefore, we aimed to synthesize the effects of VR interventions for older adults with MCI/ Mild dementia.MethodSeventy‐five subjects, with mean age 72.5±5.32 years (mean ± standard deviation), participated in this study. The subjects were randomly assigned to either control or VR intervention groups. The intervention group performed series of 4 types of VR based cognitive training program for 6 weeks. Three sessions were held per week and each session lasted for 90 minutes. Cognitive function was assessed with Mini mental state examination (MMSE) test, Trail making test (TMT) A &amp; B, and Digit symbol substitute test. Resting state EEG was measured in eyes open and eyes closed condition for 5 minutes each with 19 channel wireless EEG device. Socio‐demographic characteristics data like education, age, and smoking, and physical function data like short physical performance battery (SPPB), gait speed, were also acquired.ResultThe scores on TMT B improved in intervention group after 6 weeks of VR training compared to control group. The intervention group, in resting state EEG, showed improved theta to beta ratio (TBR) in frontal region of the brain.ConclusionVR intervention is useful in individuals with MCI or mild dementia and these findings demonstrate that VR‐intervention program is useful to improve cognitive and brain function, and physical function and gait speed in patients with cognitive decline. In future, longer and broader VR‐based studies are required to unfold a path to magnify the benefits of VR‐intervention for improving cognitive functions.

The MEMOWAVE project: A phase I/II clinical trial targeting treatment of mild cognitive impairment through sound stimulation during slow‐wave sleep

AbstractBackgroundMild Cognitive Impairment (MCI) is a highly prevalent syndrome especially among the elderly, but its treatment remains challenging. The MEMOWAVE project is a phase I/II randomized, double blind and cross‐over clinical trial. The first objective is to validate the safety and tolerance of a device consisting of a small microphone, also equipped with electroencephalographic electrodes, inserted in the external ear canals. The device produces pink noises during slow‐wave sleep based on real‐time EEG acquisition. The second objective is to investigate the effectiveness of this device in amplifying cerebral slow waves during sleep through sound emission. The third objective is to study the effect of this stimulation on memory consolidation, attention, executive functions, insight, creativity and mood in patients with MCI. Indeed, there is converging evidence that deep slow‐wave sleep plays a major role in these aspects. This process has already shown improvements in memory performance in healthy subjects and during normal aging.MethodTwenty‐four patients between 40 and 85 years of age will spend three nights in a Center for sleep disorders. Their cognitive functions, insight, creativity abilities and mood will be tested before and after a night of slow wave stimulation or placebo (device in place without stimulation), in a randomized and crossover fashion.ResultWe expect that this device will represent a simple therapeutic approach, easily tolerable by the patient, and able, if successful, of being offered quickly to a larger population of patients with MCI.ConclusionWe are proposing a new innovative methodology for the treatment of MCI which we are going to test for safety and efficacy.

The solely A+ CSF Aβ42/40 ratio using Elecsys® assays performs similar to A/T and A/N ratios in predicting amyloid PET positivity

AbstractBackgroundpTau181/Aβ42 (A+/T+ as per A/T/(N) classification) and tTau/Aβ42 (A+/(N)+) ratios using fully automated Elecsys® cerebrospinal‐fluid (CSF) immunoassays have been shown to perform well in distinguishing amyloid‐positivity (A+) by positron emission tomography (PET) among patients with subjective and mild to severe cognitive impairment. Higher performance has also been demonstrated for the CSF Aβ42/40 ratio compared to CSF amyloid 42 (Aβ42) alone. We aimed to further evaluate the performance of the Elecsys® Aβ42/40 ratio in a clinical cohort.MethodsFrozen (‐80°C) CSF samples from 103 patients treated in the Centre for Cognitive Disorders, Technical University of Munich were selected based on availability of visual amyloid‐PET status (n=54 PET+; 49 PET‐) determined during standard treatment around the time of CSF collection. In total, 71 patients were undergoing treatment for mild cognitive impairment (MCI) (n=44) or mild to moderate dementia (n=27) due to Alzheimer’s disease (AD) and 32 patients for non‐AD related fronto‐temporal lobar degeneration (n=17), MCI (n=8), depression (n=5), alcohol dependence (n=1), or subjective cognitive impairment (SCD) (n=1). CSF was measured using Elecsys® assays. CSF status for Aβ42 , pTau181/Aβ42 , and tTau/Aβ42 CSF (positive/negative) was determined based on pre‐defined biomarker cutoffs previously established using a different pre‐analytical protocol in MCI/SCD patients with suspected AD (CSF positive if Aβ42&lt;1000 pg/ml, pTau181/Aβ42&gt;0.024, and tTau/Aβ42&gt;0.028). Sensitivity and specificity were calculated for CSF‐cutoff‐based status and ROC analysis was performed to determine AUC each versus visual amyloid‐PET status.ResultsPre‐defined biomarker thresholds were considered off‐label due to deviation from recommended sample collection protocol and storage parameters. Point estimates for sensitivity and specificity for each biomarker were; CSF Aβ42 alone (sensitivity = 0.93, specificity = 0.57), pTau181/Aβ42 (0.96, 0.69), and tTau/Aβ42 (0.92, 0.69). For AUC point estimates (95% confidence interval) were; CSF Aβ42 alone [0.78 (0.68‐0.88)], pTau181/Aβ42 [0.88 (0.81‐0.95)], tTau/Aβ42 [0.87(0.80‐0.95)], and Aβ42/40 [0.90 (0.83‐0.95)].ConclusionFully automated Elecsys® cerebrospinal fluid (CSF) immunoassay predicted amyloid positivity with high accuracy. In this study, the solely A+ marker CSF Aβ42/40 ratio outperformed Aβ42 alone and performed similarly to Tau ratios. These results support those of previous studies showing high performance for the non‐Tau marker CSF Aβ42/40.

Neuroimaging methods in the randomized pivotal study of Renew NCP‐5 for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease or mild dementia of the Alzheimer's type

AbstractBackgroundVascular disease and even subclinical variation in vascular health are known contributors to cognitive impairment and hasten the progression of symptoms in individuals with Alzheimer’s disease. Recent trials have demonstrated the therapeutic benefit of pharmacological treatments for enhancing vascular health on the incidence of cognitive impairment and on the progression of vascular brain injury measured by magnetic resonance imaging (MRI). Thus, novel vascular therapeutics provide a promising approach to slowing or preventing impairment in older adults. RenewTM NCP‐5 is an FDA‐cleared, external counterpulsation (ECP) device used clinically to improve coronary and peripheral vascular hemodynamics by sequential compression and decompression of vascular beds in synchrony with the cardiac cycle. ECP is currently used to treat patients with chronic angina and congestive heart failure and has been demonstrated to alter cerebral hemodynamics.MethodNeuroimaging was coordinated across 12 sites (10 in the US and 2 outside of the US) for safety screening as well as for acquisition of exploratory neuroimaging markers of disease stage and treatment modification. Imaging protocols were in created based on a modified cross‐platform protocols developed for the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Additional sequences were added for safety. Coded data are uploaded to the central imaging coordinating site (CICS) at Massachusetts General Hospital. Patient characterization and exploratory outcome measures include T1‐weighted hippocampal volume measures and arterial spin labeling (ASL)‐based measures of cerebral blood flow (CBF). Imaging protocols include phantom scanning and test‐retest at each scan session to evaluate platform specific data quality. Imaging is performed at baseline, 6 months, and 12 months after initial treatment.ResultImaging has been performed on 214 individuals to date with 76 6 month and 6 12‐month scans. The imaging protocol is tolerated with minimal motion. ASL imaging is variable quality across scanners due to differences in hardware, software, and imaging support. This study is ongoing and initial study analyses are expected by November 2020.ConclusionRenewTM NCP‐5 treatment in Alzheimer's disease may impact cerebral hemodynamics and the ongoing clinical trial will test the effect of this treatment on cognitive symptoms as well the impact on Alzheimer’s or vascular‐associated disease processes in the brain.