Minimal Cognitive Impairment Research Articles

Photobiomodulation's potential as a non-invasive therapy for alzheimer's disease and minimal cognitive impairment: A 12-week investigation

BackgroundAlzheimer's Disease (AD), undergoing a faster increase in occurrence than any other type of dementia, lacks a curative remedy despite advanced discoveries. To explore the realm of non-pharmacologic therapies, our study evaluates the 12-week impact of non-invasive Photobiomodulation (PBM) on cognitive and psychological aspects in individuals with AD and minimal cognitive impairment (MCI). The urgency of exploring innovative interventions is underscored by the rising occurrence of AD, particularly in regions with aging populations like Iran. Method13 patients (6 case patients and 7 control patients) participated in the study. Sham treatment was administered to seven individuals, while another six received PBM treatment over 12 weeks, with daily at-home LED (810 nm wavelength) device usage lasting 20 min. Initially, the patient and their caregiver participated in two hospital sessions to acquaint them with the device's operation. ResultsThe mean reduction of Hamilton's anxiety questionnaire score was 3.33±6.08 in the intervention group and 2.00±3.46 in the control group (p-value=0.836). The mean score reduction of the Hamilton depression questionnaire was 3.16±3.86 in the intervention group and 4.85±6.20 in the control group (p-value=0.836). The mean score of the DAD questionnaire in the intervention group before the study was 25.50±13.13 and after the intervention was 29.83±12.12 (p-value=0.084) and in the control group it was 29.71±8.19 and after the study was 29±0.972 (p-value = 0.526). The mean changes in the DAD questionnaire score in the intervention group increased by 4.33±4.92 and decreased by 0.71±2.81 in the control group (p-value=0.041). ConclusionIn general, PBM appears to hold promise as a potentially safe method for enhancing the cognitive, functional, and psychological status of individuals with Alzheimer's disease, though further research with larger sample size and cautious interpretation are warranted.

How to Use the New European Academy of Neurology/Movement Disorder Society European Section Guideline for Invasive Therapies in Parkinson's Disease.

The decision to choose invasive treatments for Parkinson's disease (PD) is complex and needs careful consideration. Although the recommendations of the European Academy of Neurology/Movement Disorder Society European Section guideline for invasive therapies of PD are useful, the different clinical profiles of people with PD who seek advice for possible invasive therapy need further attention. Here we describe 8 clinical standard situations of people with PD unsatisfied with their current oral treatment where invasive therapies may be considered. These are PD patients presenting with the following symptoms: (1) severe motor fluctuations, (2) beginning of levodopa-responsive fluctuations, severe tremor at (3) young or (4) advanced age, (5) impulse control disorders and related behavioral disorders, (6) hallucinations and psychosis, (7) minimal cognitive impairment or mild dementia, and (8) patients in need of palliative care. For some of these conditions, evidence at lower level or simple clinical considerations exist. There are no one-fits-all answers, but physician and patient should discuss each option carefully considering symptom profile, psychosocial context, availability of therapy alternatives, and many other factors. The current paper outlines our proposed approach to these circumstances.

Structural and Metabolic Retinal Changes Associated With Mild Cognitive Impairment in Type 2 Diabetes.

Type 2 diabetes is associated with mild cognitive impairment (MCI). Therefore, retinal and cerebral neurodegeneration may run in parallel. To assess whether there was a difference in retinal structure, vessel, and metabolic parameters in individuals with MCI. We found those with MCI had a thinner macular retinal nerve fiber layer, macular ganglion cell layer, and less venular oxygen saturation. We suggest noninvasive retinal markers may be useful to detect those at risk of cognitive dysfunction.

A systematic review and meta-analysis on the association between orthostatic hypotension and mild cognitive impairment and dementia in Parkinson's disease.

Cognitive impairment is a frequent disabling feature of Parkinson's disease (PD). Orthostatic hypotension (OH) is treatable and may be a risk factor for cognitive impairment. We conducted a systematic review and meta-analysis to examine the relationship between OH with PD-associated minimal cognitive impairment (PD-MCI) and dementia (PDD) and assess the mitigating effects of potential confounding factors. Observational studies published in English, Spanish, French, or Portuguese up to January 2022 were searched for in PubMed, EBSCO, and SciELO databases. The primary aim of this study was to revise the association between OH with PD-MCI and PDD. Alongside, we assessed OH as related to cognitive rating scales. Fixed and random models were fitted. Meta-regression was used to assess the mitigating effects of confounding variables. We identified 18 studies that reported OH association with PDD or PD-MCI, 15 of them reporting OH association with cognitive rating scales. OH was significantly associated with PDD/PD-MCI (OR, 95% CI: 3.31, 2.16-5.08; k = 18, n = 2251; p < 0.01). OH association with PDD (4.64, 2.68-8.02; k = 13, n = 1194; p < 0.01) was stronger than with PD-MCI (1.82, 0.92-3.58; k = 5, n = 1056; p = NS). The association between OH and PD-MCI/PDD was stronger in studies with a higher proportion of women and in those with a lower frequency of supine hypertension. Global cognition rating scale scores were lower in patients with OH (SMD, 95% CI: - 0.55, - 0.83/ - 0.26; k = 12, n = 1427; p < 0.01). Orthostatic hypotension shows as a significant risk factor for cognitive impairment in PD, especially in women and patients not suffering from hypertension.

What's in a name?

AbstractBackgroundThere is precedent in the AD field for confusion and dissonance due to the naming of clinical phenomena. Early on, Alzheimer's disease (AD) or Alzheimer's dementia could mean anyone with progressive dementia, and did not require the application of standardised criteria. As standardisation improved at the stage of dementia, the terms Mild Cognitive Impairment or Minimal Cognitive Impairment came into usage and the clinical conditions encompassed by these terms were variably named and defined in different nomenclature systems (eg., AAN, DSM, ICD) and required different criteria depending upon the definitions used by different academic working groups. A similar controversy now exists regarding the naming of individuals who have biological markers consistent with AD, but do not have any clinical symptoms or functional decline from baseline.MethodOther speakers in this symposium will review the history and advocate for particular approaches to describing individuals who have AD biological markers bur are cognitively unimpaired. This presentation will respond to those arguments and bring in additional external perspectives from experience as a clinician treating patients, as a researcher performing non‐interventional trials, and a drug developer.ResultThe implications of naming the condition preclinical AD versus individuals at risk for AD will be explicated for clinical practice, general research, and clinical trials.ConclusionTBD.

Genistein effect on cognition in prodromal Alzheimer’s disease patients. The GENIAL clinical trial

BackgroundDelaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics.Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model.MethodsIn this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer’s disease patients. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test.ResultsWe report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p = 0.031; dichotomized delayed Centil REY copy p = 0.002 and a tendency to improve in all the rest of them.The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878), while placebo-treated did increase it (p = 0.036). We did not observe significant changes in other brain areas studied.ConclusionsThis study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer’s dementia in patients with prodromal Alzheimer’s disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.Trial registrationNCT01982578, registered on November 13, 2013.

EXPERIENCE OF USING ECMO IN CHILDREN WITH SEVERE COVID-19 (DESCRIPTION OF CLINICAL CASES)

Summary: Among pediatric patients with COVID-19, about 0,8-1 % require admission to the intensive care unit. The main syndromes that determine the severe course and mortality in children are acute respiratory distress syndrome, multisystem inflammation syndrome and multiple organ failure. In our report, we present two clinical cases of successful use of ECMO in children with COVID-19 who have developed acute respiratory distress syndrome. Description of clinical cases. Children aged 3 years (case 1) and 17 years (case2) were admitted to the intensive care unit with signs of severe respiratory failure. Both patients were diagnosed with SARS-CoV-2 virus infection. Traditional methods of respiratory support in combination with prone position ventilation and myoplegia have not improved oxygenation. With PaO2 / FiO2 – 60 (case 1) and PaO2 / FiO2 – 75 (case 2), children were started V-V ECMO. The duration of ECMO in both patients was 7 days. As a result, improved oxygenation was achieved: PaO2 / FiO2 – 310 (case 1), PaO2 / FiO2 – 264 (case 2) after decannulation, as well as the condition of pulmonary mechanics (Cst increased from 8 to 22 ml / cmH2O in the first case and from 15 ml / cmH2O to 57 ml / cmH2O in the second case, both patients survived and were discharged with minimal cognitive impairment. Conclusion: In cases where critical hypoxemia caused by severe ARDS is not eliminated by traditional methods of respiratory support, ECMO can be an effective rescue technology.

Preserved visuospatial abilities in absence of the right hemisphere: A case of cerebral hemiatrophy with minimal cognitive impairment

Cerebral hemiatrophy is a rare neurological condition, usually resulting in severe and diffuse cognitive impairment. In this paper we present a 69-year old woman with notable congenital hemiatrophy with strikingly preserved cognitive functions. Cognitive assessment indicated that although her executive functions were found impaired, the remaining cognitive domains were relatively unaffected. We argue that this unexpected cognitive profile may be explained by anomalous hemispheric lateralization, driven by neuroplasticity along the developmental course.

Validation of alternative dot counting test E-score cutoffs based on degree of cognitive impairment in veteran and civilian clinical samples

Objective This study examined Dot Counting Test (DCT) performance among patient populations with no/minimal impairment and mild impairment in an attempt to cross-validate a more parsimonious interpretative strategy and to derive optimal E-Score cutoffs. Method Participants included clinically-referred patients from VA (n = 101) and academic medical center (AMC, n = 183) settings. Patients were separated by validity status (valid/invalid), and subsequently two comparison groups were formed from each sample’s valid group. Namely, Group 1 included patients with no to minimal cognitive impairment, and Group 2 included those with mild neurocognitive disorder. Analysis of variance tested for differences between rounded and unrounded DCT E-Scores across both comparison groups and the invalid group. Receiver operating characteristic curve analyses identified optimal validity cut-scores for each sample and stratified by comparison groups. Results In the VA sample, cut scores of ≥13 (rounded) and ≥12.58 (unrounded) differentiated Group 1 from the invalid performers (87% sensitivity/88% specificity), and cut scores of ≥17 (rounded; 58% sensitivity/90% specificity) and ≥16.49 (unrounded; 61% sensitivity/90% specificity) differentiated Group 2 from the invalid group. Similarly, in the AMC group, a cut score of ≥13 (rounded and unrounded; 75% sensitivity/90% specificity) differentiated Group 1 from the invalid group, whereas cut scores of ≥18 (rounded; 43% sensitivity/94% specificity) and ≥16.94 (unrounded; 46% sensitivity/90% specificity) differentiated Group 2 from the invalid performers. Conclusions Different cut scores were indicated based on degree of cognitive impairment, and provide proof-of-concept for a more parsimonious interpretative paradigm than using individual cut scores derived for specific diagnostic groups.

Mastocytosis patients' cognitive dysfunctions correlate with the presence of spindle-shaped mast cells in bone marrow.

To the Editor, Mastocytosis is a hematological neoplasm with a broad spectrum of disease caused by mast cell (MC) infiltration (i.e., impairment of function of bone marrow, liver) and degranulation (i.e., anaphylaxis).1 Recent data indicate psychological factors and neurological factors.2 Patients with mastocytosis have a significantly lower quality of life and experience increased anxiety, depression, and other symptoms such as headache or fatigue.3, 4 These might be accompanied by cognitive impairment and brain fog declared by 86% of US patients, though its relation with mastocytosis and its progression hasn't been established to date.5 Some of these symptoms might result from abnormal MCs in central nervous system.6 In murine model, Esposito et al. showed that stress through corticotropin stimulates brain MCs to disrupt permeability of brain–blood barrier. This effect was absent in MC-depleted rodents and after cromolyn administration. The aim of the study was to investigate cognitive dysfunctions in patients with mastocytosis and analyze its connection with disease characteristics in patients. The group of 79 Polish patients suffering from mastocytosis was enrolled (59 women and 20 men; age 20–75) after signing written informed consent. Fifty-four of them suffered from indolent systemic mastocytosis, 2 had diffuse cutaneous mastocytosis, 20 had maculopapulous cutaneous mastocytosis, 2 had smoldering systemic mastocytosis, and there was a single patient with bone marrow mastocytosis. Serum tryptase ranged from 3 to 190 ng/ml with mean value 47.6 ng/ml. The education level of the studied population was high. Forty patients reported high education, 26 middle school, 10 vocational education, and 3 elementary. All of the patients were evaluated with Mini–Mental State Examination (MMSE) that assesses cognitive functions in 0–30 point scale.7 The cut-off point that suggests dementia is below 24 for educated populations, including Poland. All patients had bone marrow biopsy performed. Mastocytosis treatment was evaluated with WHO Performance Status; the patients were also asked about particular typical MC activation symptoms.8 Statistical analysis was conducted with Statistica software using Spearman correlation test. Cut-off point for the p-value was 0.05. The mean MMSE score was 27.8 (median 29). Six out of 79 patients (7.6%) scored below 24 points (see Figure 1). Other 16 patients (20%) scored 24–26 points, which suggests minimal cognitive impairment (MCI).7 According to performance status, 23 patients had no symptoms, 55 scored 1, and one patient scored 2. There was a positive correlation with education level (R = 0.45) and a negative one with age (R = −0.34), as expected. MMSE correlated negatively with the presence of 25% atypical spindle-shaped MCs in bone marrow (minor systemic mastocytosis criterion) with (R = −0.5) and bone pain (R = −0.45). No correlation was found between MMSE and serum tryptase level, presence of KIT bone marrow mutation, CD2/CD25 expression, skin involvement or performance status. A weak correlation was observed for the presence of CD30 (R = −0.1) and symptoms: pruritus (R = −0.13), edema (R = −0.23). There were no differences in results between patients with cutaneous and indolent systemic mastocytosis subgroups. Number of cases with results of Mini-Mental State Examination. Red color shows potential dementia; yellow color shows minimal cognitive impairment; and blue color shows normal results The results of our study are in contrast to previously done surveys by Jennings et al.5 where 86% of the sample declared cognitive dysfunctions. However, our study suggests that such high cognitive impairment prevalence could have been over-diagnosed. Using well-known, validated MMSE method, we observed that only 7.6% of the sample experienced significant cognitive impairment while total 27% presented slight cognitive abnormalities. Such high self-reported symptoms may be due to multiple emotional and personal problems, or affective disorders, that patients experience because of MC activation. Those might be misinterpreted by patients and labeled as cognitive dysfunctions. The percentage of atypical MCs and bone pain that correlated to MMSE is associated with systemic mastocytosis and usually increases as the disease progresses to an aggressive form. Interestingly, there was no relation of MMSE to serum tryptase concentration, skin involvement, and general symptoms assessed by performance status. It is possible that cognitive dysfunctions might be linked to mastocytosis aggressiveness rather than to MC activation. In such case, according to Theoharides et al., serum IL-6 might be a promising predictor of cognitive dysfunctions as it is related to MC-related osteoporosis and bone pain.9 However, further studies are required in this area. education, mast cells, quality of life bildung, lebensqualita, mastozytose, mastzelle Publication costs were covered by Medical University of Gdansk statutory funds ST 02-141/07/231. The authors declare no conflict of interests. Medical University of Gdansk, Grant/Award Number: ST 02-141/07/231

Neuroimaging and clinical characteristics of cognitive migration in community-dwelling older adults

BackgroundMultiple neuroimaging and clinical biomarkers have been identified to predict cognitive decline and clinical progression to mild cognitive impairment (MCI) or dementia. However, early biomarkers associated with transition to and reversion from cognitive impairment (cognitive migration) require further understanding. We investigated the impacts of baseline neuroimaging and clinical biomarkers on cognitive migration in a community-dwelling older cohort. MethodsWe studied 391 participants from the Wake Forest Alzheimer’s Disease Research Center Clinical Core cohort who underwent neuropsychological assessment and magnetic resonance imaging (MRI). At baseline, each participant was categorized to a functional/cognitive state using global Clinical Dementia Rating (CDR) score: CDR = 0 indicates normal cognitive function; CDR = 0.5 is minimal cognitive impairment. The primary outcome was cognitive migration status determined by CDR change between baseline and follow-up (mean difference = 13.9 months): CDR-0 Stables (no migration; maintained CDR = 0), CDR-0.5 Stables (no migration; maintained CDR = 0.5), Migrants− (negative migration; CDR 0 to CDR 0.5), and Reverters+ (positive migration; CDR 0.5 to CDR 0). Baseline T1-weighted MRI was analyzed for gray matter (GM) volume using voxel-based morphometry (VBM). For VBM, we used a two-sample t-test controlling for age, sex, education years and intracranial volume for group comparisons: CDR-0 Stables vs CDR-0.5 Stables, CDR-0 Stables vs Migrants−, CDR-0.5 Stables vs Reverters+ and Migrants− vs Reverters+ (thresholded at k = 30 voxels, p <.01 uncorrected). Oral Glucose Tolerance Testing (OGTT-2h) assessed blood glucose 120-minute post challenge. Multinomial logistic regression estimated average predicted probabilities of cognitive migration status using OGTT-2h and age range (55–65, 65–75 and 75+) as predictors. ResultsVBM analyses revealed lower GM volume in inferior and middle temporal gyri, hippocampus, parahippocampal gyrus, and superior and inferior frontal regions in Migrants− and CDR-0.5 Stables. Predicted probabilities indicated that individuals aged 55–65 with normal OGTT-2h levels were more likely to have better cognitive migration status (e.g., CDR-0 Stables or Reverters+) than those aged 75+ with high OGTT-2h. ConclusionsLower GM volumes and high OGTT-2h glucose levels may predict worse cognitive migration status in early stages of disease. The opposite is true for better cognitive migration. Validating these biomarkers may guide clinical diagnosis and treatments.

The Effects of 3D Immersion Technology (3Scape) on Mental Health in Outpatients From a Short-Term Assessment, Rehabilitation, and Treatment Program: Feasibility Protocol for a Randomized Controlled Trial.

BackgroundMental health conditions are prevalent among Canadians and are a leading cause of disability. Each year, 1 in 5 Canadians experiences a mental health issue. A total of 5% of people aged ≥65 years perceive their mental health as fair or poor, and 6.3% of them have mood disorders. Regarding older adults with cognitive impairments such as dementia, up to 40%-50% of them experience depression at some point. We believe that older adults can benefit significantly from information and telecommunication technologies as a strategy for improving mental health conditions such as depression and anxiety, while simultaneously improving their quality of life. 3Scape Systems Inc is an Alberta-based private company that has produced a series of specialized 3D videos designed to simulate real-life events and engage individuals living with mental health disorders and cognitive impairments such as dementia.ObjectiveThis study aims to explore the trial design and effects of 3Scape videos on older adults’ symptoms of depression and anxiety and the efficacy of this technology in improving the quality of life of patients attending the Short-Term Assessment, Rehabilitation, and Treatment Psychiatry Day Hospital program at Glenrose Rehabilitation Hospital and to provide data to estimate the parameters required to design a definitive randomized controlled trial.MethodsThe trial will use a randomized controlled design comprising 15 intervention participants and 15 control group participants. The participants will be adults aged ≥65 years who are cognitively intact or have minimal cognitive impairment (ie, Montreal Cognitive Assessment score ≥18), and are clients of the Short-Term Assessment, Rehabilitation, and Treatment Psychiatry Day Hospital program at Glenrose Rehabilitation Hospital. This study’s primary outcome variables are related to clients’ depressive and anxiety symptoms and their quality of life. The control group will receive the standard of care (ie, the Short-Term Assessment, Rehabilitation, and Treatment Psychiatry Day Hospital program at Glenrose Rehabilitation Hospital). The intervention group will receive the same standard of care as the control group and will use 3Scape Systems videos for therapeutic activities.ResultsOur study is currently on hold because of the COVID-19 pandemic. The recruitment process is expected to resume by November 2021, and the primary impact analysis is expected to be conducted by February 2022.ConclusionsThis study will provide valuable information such as the measurement of comparative intervention effects, perception of older adults and mental health therapists about the 3Scape Systems, the associated costs of treatment, and product costs. This will contribute to the evidence planning process, which will be crucial for the future adoption of 3Scape Systems.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 93685907; https://www.isrctn.com/ISRCTN93685907.International Registered Report Identifier (IRRID)PRR1-10.2196/25017

Machine Learning Detects Distinct Subtypes of Minimal Cognitive Impairment

Machine Learning Detects Distinct Subtypes of Minimal Cognitive Impairment

The Use of ECT in a Geriatric Patient with a Deep Brain Stimulator

<h3>Introduction</h3> Electroconvulsive therapy (ECT) is a commonly used and effective treatment for major depressive disorder with psychosis, especially in the geriatric population. Depressive disorders have significant prevalence in those with movement disorders including Parkinson's disease. Deep-brain stimulators are an effective treatment for Parkinson's disease, however, few cases in the literature exist about the use of ECT in patients with deep-brain stimulators. <h3>Methods</h3> A 68-year-old man with Parkinson's disease with a deep-brain stimulator (DBS) is seen in an outpatient geriatric psychiatry clinic. He has severe major depressive disorder with psychosis. The patient's clinical features include depressed mood, hopelessness, anhedonia, poor sleep, and poor appetite with weight loss. He endorses delusions of worsening physical and functional ability as well as delusions of abandonment and impoverishment. The patient experienced suicidal thinking and had impulsive para-suicidal behavior. The patient's symptoms are minimally responsive to treatment with antidepressants (Escitalopram, Mirtazapine, and Duloxetine) as well as psychotherapy. The patient's Parkinson's disease is treated with carbidopa-levodopa and a St. Jude DBS in his subthalamic nucleus, which was placed almost two years earlier. An ECT consultation was pursued in conjunction with discussion with the patient's neurologist. The patient begins undergoing acute bifrontal ECT with his DBS switched off for his treatments. <h3>Results</h3> The patient has, thus far, had 12 bifrontal acute phase ECT treatments, with the first 10 treatments occurring biweekly and then weekly. He is tolerating ECT well with minimal cognitive impairment immediately after the treatment and no complications relating to his DBS. After three treatments, the patient began experiencing significant improvements in mood, appetite, and sleep noted by himself and collateral sources. After 10 treatments the patient's suicidality and psychotic symptoms had resolved. The patient is much more active and has an improved level of functioning. His family notes that after over a year of severe depression, he finally is "back to himself." <h3>Conclusions</h3> ECT is an appropriate and effective treatment for major depressive disorder with psychosis in patients with concomitant Parkinson's disease who have a DBS. Although there are very few case reports of prescribing ECT to treat patients with Parkinson's disease that have a DBS device, this case demonstrates that it is a safe and efficacious treatment that should be considered. It is especially important to consider this treatment if there is a lack of response to antidepressants. When patients with DBS are not offered ECT due to reluctance and safety concerns, these patients are deprived of a valuable treatment option. <h3>Funding</h3> Not applicable

41224 REDUCED FRONTOSTRIATAL FUNCTIONAL CONNECTIVITY IN 41- TO 70-YEAR-OLD ADULTS WITH HIV

ABSTRACT IMPACT: The knowledge acquired from my research can inform the development of early diagnostic methods for HIV-associated neurocognitive disorders. OBJECTIVES/GOALS: In the era of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains high but the neural mechanisms are unclear. We examined whether older people with HIV (PWH) with minimal cognitive impairment have reduced functional connectivity in frontostriatal circuits compared to controls. METHODS/STUDY POPULATION: 99 PWH (mean age 56.6 years, 75% male, 62% Black, mean duration of HIV-infection 26.2 years ±9.3, 90% viral load &lt;50 copies, 98% on stable cART) and 38 demographically-comparable controls (mean age 54.5 years, 71% male, 58% Black) participated in a cross-sectional study. A 7-domain neuropsychological battery and an Activities of Daily Living index were used to determine HAND diagnoses: 32 PWH met criteria for asymptomatic to mild HAND. Motor skill was assessed using the Grooved Pegboard Test by measuring performance speed. Structural MRI and resting-state functional MRI were collected. Seed-to-voxel analyses were conducted using 4 distinct regions in the striatum as seed regions. We used a voxel threshold of p&lt;0.001 and cluster threshold of p&lt;0.05 (FDR-corrected) after controlling for demographic variables. RESULTS/ANTICIPATED RESULTS: Compared to controls, PWH had lower resting state functional connectivity between the default mode region of the striatum (i.e., medial caudate) and bilateral superior frontal gyrus, supplementary motor cortex and paracingulate gyrus (p&lt;0.05; cluster size: 567 voxels). Also, compared to controls, PWH had reduced resting state functional connectivity between the motor division of the striatum (i.e., posterior putamen) and anterior cingulate cortex and left supplementary motor cortex (p&lt;0.05, cluster size: 405 voxels). Performance speed on the Grooved Pegboard motor test negatively correlated with functional connectivity between the motor region of the striatum and supplementary motor frontal regions in all participants (Spearman’s rho=-0.18, p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results support the hypothesis that frontostriatal abnormalities are widely present in PWH and might play a key role in HAND development. Our data suggest that dysfunction within the frontostriatal circuits may be involved in motor impairment in PWH, and ongoing inflammation may contribute to motor impairment and frontostriatal injury.

Identifying gene expression signatures in individuals with minimal cognitive impairment in the presence of advanced Alzheimer's disease pathology

AbstractBackgroundThe pathological hallmarks of Alzheimer’s disease such as amyloid plaques and neurofibrillary tau tangles are usually associated with the primary clinical manifestation of cognitive decline. Recent studies implicate that a subset of “resistant” individuals have high burden of AD pathology, yet do not exhibit dementia (cognitive decline). Here, we compared the publicly available gene expression profiles of these resilient individuals and susceptible individuals (showing both AD pathology and cognitive decline) in dorsolateral prefrontal cortex (DLPFC) brain tissue obtained from individuals enrolled in the Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP).MethodWe conducted bulk RNA‐Seq analysis on data from the DLPFC of 239 individuals with differing AD pathological findings and clinical consensus diagnosis. This data set is available through the Synapse portal (AMP‐AD consortium). The patients were subdivided into four groups of control, weakly resilient, strongly resilient, and susceptible, according to their degree of pathology (Braak stage) and clinical cognitive diagnosis. The control group included individuals with no cognitive impairment and initial braak stages; 0 and 1. The weakly and strongly resilient groups included individuals with no and mild cognitive impairment with advanced Braak stages respectively, while the susceptible group comprised individuals with AD‐dementia and advanced tauopathy (Braak stage&gt;4). We used DESeq2 between these groups with a multiple factor approach that corrected for sex and age of death.ResultOur findings provide insight into genes that may be attributable to weak or strong resilience in the presence of relatively advanced AD pathology. Some of these candidate genes, such as SERPINA5 and GIPR, have previously been associated AD pathology and other neurodegenerative diseases, but we also identified a set of less well‐characterized genes that may be involved in cognition specific contributions to AD resilience.ConclusionOur study recapitulates genes with known associations with AD pathology, and also identifies new candidate genes and pathways worth pursuing further as potential therapeutic targets to mitigate cognitive decline associated with AD. As ongoing proteomics and snRNA‐seq data is generated, these candidates may be further refined through an integrative approach, yielding new insights into pathways involved in AD pathology‐mediated decline and cognitive resilience.

Can Melatonin Be a Potential "Silver Bullet" in Treating COVID-19 Patients?

The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Moreover, indirect evidence points out to a possible antiviral action of melatonin by interfering with SARS-CoV-2/angiotensin-converting enzyme 2 association. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. As a cytoprotector, melatonin serves to combat several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease. In view of evidence on the occurrence of neurological sequels in COVID-19-infected patients, another putative application of melatonin emerges based on its neuroprotective properties. Since melatonin is an effective means to control cognitive decay in minimal cognitive impairment, its therapeutic significance for the neurological sequels of SARS-CoV-2 infection should be considered. Finally, yet importantly, exogenous melatonin can be an adjuvant capable of augmenting the efficacy of anti-SARS-CoV-2 vaccines. We discuss in this review the experimental evidence suggesting that melatonin is a potential “silver bullet” in the COVID 19 pandemic.

The Expression of Activin Receptor-Like Kinase 1 (ACVRL1/ALK1) in Hippocampal Arterioles Declines During Progression of Alzheimer’s Disease

Cerebral amyloid angiopathy (CAA) in Alzheimer’s disease (AD)—deposition of beta amyloid (Aβ) within the walls of cerebral blood vessels—typically accompanies Aβ buildup in brain parenchyma and causes abnormalities in vessel structure and function. We recently demonstrated that the immunoreactivity of activin receptor-like kinase 1 (ALK1), the type I receptor for circulating BMP9/BMP10 (bone morphogenetic protein) signaling proteins, is reduced in advanced, but not early stages of AD in CA3 pyramidal neurons. Here we characterize vascular expression of ALK1 in the context of progressive AD pathology accompanied by amyloid angiopathy in postmortem hippocampi using immunohistochemical methods. Hippocampal arteriolar wall ALK1 signal intensity was 35% lower in AD patients (Braak and Braak Stages IV and V [BBIV-V]; clinical dementia rating [CDR1-2]) as compared with subjects with early AD pathologic changes but either cognitively intact or with minimal cognitive impairment (BBIII; CDR0-0.5). The intensity of Aβ signal in arteriolar walls was similar in all analyzed cases. These data suggest that, as demonstrated previously for specific neuronal populations, ALK1 expression in blood vessels is also vulnerable to the AD pathophysiologic process, perhaps related to CAA. However, cortical arterioles may remain responsive to the ALK1 ligands, such as BMP9 and BMP10 in early and moderate AD.

A prospective study of the cognitive and psychiatric effects of pituitary tumours and their treatments

Neurocognitive complaints are common in patients with pituitary tumours, particularly in memory and concentration. Past studies have shown impairments in executive function and memory, but it is not clear whether these result from direct effects of the tumour (pressure or hormonal secretion), incidental damage from radiotherapy or surgical treatments, and/or mediating psychiatric factors. This study assessed cognitive function and psychiatric state of 86 pituitary tumour patients and 18 healthy controls, pre and post-treatment, to examine the effects of tumour aetiology and treatment type. No significant cognitive impairments were found, except on verbal recognition memory. Patients with Cushing’s disease showed lower verbal recognition memory than the other groups pre-treatment, but improved at follow-up. This was (at least partially) accounted for by an improvement in depression scores. Patients who were treated with surgery showed poorer verbal recognition memory than controls across all (pre- and post-treatment) time-points. Overall findings of minimal cognitive impairment in patients with pituitary tumours may reflect improved diagnostic and treatment techniques in recent years. We suggest that the verbal memory impairments identified in the Cushing’s group may result from increased cortisol (directly, or mediated by depression). In the surgical groups, verbal memory impairments appeared to pre-date treatment. This may relate to treatment selection factors, rather than harmful effects of surgery itself.

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.