Music Therapy as a Complementary Treatment in Patients with Dementia Associated to Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease (AD) is a complex condition that affects various aspects of a patient's life. Music therapy may be considered a beneficial supplementary tool to traditional therapies, that not fully address the range of AD manifestations. Objective: The purpose of this systematic review is to investigate whether music therapy can have a positive impact on AD patients and on which symptoms. Methods: The main research databases employed have been PubMed and Cochrane, using the keywords "dementia", "music therapy", "Alzheimer", "fMRI", "music", and "EEG". Results: After removing duplicates and irrelevant studies, 23 were screened using set criteria, resulting in the final inclusion of 15 studies. The total number of participants included in these studies has been of 1,196 patients. For the fMRI analysis the search resulted in 28 studies on PubMed, two of which were included in the research; the total number of participants was of 124 individuals. The studies conducted with EEG were found using PubMed. The initial search resulted in 15 studies, but after a more accurate evaluation only 2 have been included in the analysis. Conclusions: Even though the data currently available is not sufficient to draw conclusions supported by robust statistical power, the impact of music therapy on AD neuropsychiatric symptoms deserves great interest. Further research should be ushered, possibly multicentric studies, led with neuroimaging and other recent techniques, which can eventually open views on the music role in improving the cognitive status in AD.

Risk of Incident Atrial Fibrillation and Subsequent Use of Oral Anticoagulants in Patients with Dementia.

BACKGROUND: Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes. METHODS: Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group). RESULTS: The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching. CONCLUSION: In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events.

Acoustic stimulation as a promising technique to enhance slow-wave sleep in Alzheimer's disease: results of a pilot study.

STUDY OBJECTIVES: Sleep disturbances are common in people with Alzheimer's disease (AD), and a reduction in slow-wave activity is the most striking underlying change. Acoustic stimulation has emerged as a promising approach to enhance slow-wave activity in healthy adults and people with amnestic mild cognitive impairment. In this phase 1 study we investigated, for the first time, the feasibility of acoustic stimulation in AD and piloted the effect on slow-wave sleep (SWS). METHODS: Eleven adults with mild to moderate AD first wore the DREEM 2 headband for 2 nights to establish a baseline registration. Using machine learning, the DREEM 2 headband automatically scores sleep stages in real time. Subsequently, the participants wore the headband for 14 consecutive "stimulation nights" at home. During these nights, the device applied phase-locked acoustic stimulation of 40-dB pink noise delivered over 2 bone-conductance transducers targeted to the up-phase of the delta wave or SHAM, if it detected SWS in sufficiently high-quality data. RESULTS: Results of the DREEM 2 headband algorithm show a significant average increase in SWS (minutes) [t(3.17) = 33.57, P = .019] between the beginning and end of the intervention, almost twice as much time was spent in SWS. Consensus scoring of electroencephalography data confirmed this trend of more time spent in SWS [t(2.4) = 26.07, P = .053]. CONCLUSIONS: Our phase 1 study provided the first evidence that targeted acoustic stimuli is feasible and could increase SWS in AD significantly. Future studies should further test and optimize the effect of stimulation on SWS in AD in a large randomized controlled trial. CITATION: Van den Bulcke L, Peeters A-M, Heremans E, et al. Acoustic stimulation as a promising technique to enhance slow-wave sleep in Alzheimer's disease: results of a pilot study. J Clin Sleep Med. 2023;19(12):2107-2112.

Increased TSPO expression, pyroglutamate-modified amyloid beta (AßN3(pE)) accumulation and transient clustering of microglia in the thalamus of Tg-SwDI mice.

Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aß in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies. In the present study, we documented interesting new features in the thalamus of Tg-SwDI mice: 1) a sharp increase in the expression of ionized calcium-binding adapter molecule 1 (Iba-1) in microglia in 6-month-old animals; 2) microglia clustering at six months that disappeared in old animals; 3) N-truncated/modified AßN3(pE) peptide in 9-month-old female and 12-month-old male mice; 4) an age-dependent increase in translocator protein (TSPO) expression. These findings reinforce the versatility of this model for studying multiple pathological issues involved in AD and CAA.

Potential Neuroprotective Effects of Dietary Omega-3 Fatty Acids on Stress in Alzheimer's Disease.

BACKGROUND: A large number of individual potentially modifiable factors are associated with risk for Alzheimer's disease (AD). However, less is known about the interactions between the individual factors. METHODS: In order to begin to examine the relationship between a pair of factors, we performed a pilot study, surveying patients with AD and controls for stress exposure and dietary omega-3 fatty acid intake to explore their relationship for risk of AD. RESULTS: For individuals with the greatest stress exposure, omega-3 fatty acid intake was significantly greater in healthy controls than in AD patients. There was no difference among those with low stress exposure. CONCLUSIONS: These initial results begin to suggest that omega-3 fatty acids may mitigate AD risk in the setting of greater stress exposure. This will need to be examined with larger populations and other pairs of risk factors to better understand these important relationships. Examining how individual risk factors interact will ultimately be important for learning how to optimally decrease the risk of AD.

Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance.

BACKGROUND: The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent. AIM: The aim of this study was to investigate the associations of vitamin B12-related markers with CSF biomarkers of AD and cognitive performance. METHODS: Data included 462 patients aged 40 to 94 years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid ß42 (Aß42 ) and total-tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations. RESULTS: In the multi-adjusted model, higher levels of MMA were associated with raised CSF total-tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI = 1.35-7.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower Aß42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22-7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning. CONCLUSIONS: Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. ANN NEUROL 2023;94:223-231.

A randomized, open-label clinical trial in mild cognitive impairment with EGb 761 examining blood markers of inflammation and oxidative stress.

Although beta-amyloid (Aß) and phosphorylated tau remain the preferred targets for disease-modifying treatments (DMT) against Alzheimer's disease (AD), part of the pathophysiological mechanisms of cognitive impairment are related to neuroinflammation and oxidative stress. In mild cognitive impairment (MCI), a prodromal stage of AD and other neurodegenerative conditions, the joint appearance of inflammation, oxidative stress, and metabolic alterations are the common pathways of neurotoxicity and neurodegeneration. The standardized extract of Ginkgo biloba EGb 761 interferes with the pathogenic mechanisms involved in both the development of cognitive impairment due to AD and that of vascular origin. The primary objective of this study is to compare changes in the levels of blood markers of inflammation and oxidative stress after treatment with EGb 761 in a cohort of 100 patients with MCI. In addition, we aim to assess changes in these blood markers during an additional 12-month extension phase in which patients in the control group will also receive EGb 761 and patients in the active group will extend their treatment duration. Secondary objectives include comparing changes in neuropsychiatric and cognitive test scores between the baseline (v0) and 12-month visits (v2). This study is a Phase IV, single-center, randomized, open-label, parallel-group clinical trial consisting of the 12-month follow-up of a cohort of participants with MCI [Global Deterioration Scale (GDS) = 3] and an extension with an additional 12-month follow-up. During the first 12 months, participants will be randomized into two arms: in one arm, patients will receive 1 daily tablet of EGb 761 240 mg orally (study group, n = 50), while in the other arm, patients will not receive EGb 761 and will undergo the same assessments as the treated group (control group, n = 50). After the first 12 months of the study, patients in the EGb 761-treated group will continue treatment, and patients in the control group will be offered one EGb 761 240 mg tablet per day orally. All participants will be monitored for an additional 12 months. A battery of blood markers of inflammation and oxidative stress will be quantified at v0, v1, v2, v3, and v4. The Olink Proteomics panel of inflammation markers ( https://www.olink.com/products/inflammation/ ) will be used to evaluate 92 proteins associated with inflammatory diseases and related biological processes. The second panel measures 92 proteins involved in neurological processes. At v0, v2, and v4, neuropsychological and neurological evaluations will be conducted in addition to vital signs and anthropometric studies using a body composition monitor with bioimpedance technology (Tanita). Sixty percent of the 100 MCI patients recruited were women. The mean age was 73.1 years, and the mean time between symptom onset and MCI diagnosis was 2.9 years. The mean Mini-Mental State Examination (MMSE) score was 26.7. Depressive and anxiety disorders, as well as vascular risk factors, were the most frequent comorbidities among the cohort. The study is still ongoing, and results for the first year of treatment (v0, v1, v2) are expected by 2023. Individuals with MCI have an elevated risk of developing dementia. EGb 761 is used worldwide for the symptomatic treatment of cognitive disorders due to its neuroprotective effects. In experimental models and clinical observational studies, EGb 761 has shown strong antioxidant and anti-inflammatory activity. As a result, this study has been proposed to evaluate the antioxidant and anti-inflammatory effects on plasma markers and their potential clinical correlation with the progression of cognitive decline in patients with MCI.Trial registration: Registro Español de estudios clínicos (REec) number 2020-003776-41, ClinicalTrials.gov Identifier: NCT05594355.

Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss.

Objectives: Ten million new cases of dementia are recorded annually worldwide, with agitation and idiopathic weight loss being the most common symptoms. Several pharmacological therapies have emerged in recent years, but the clinical use of cannabis extracts in older patients with AD is constantly growing. This retrospective, analytical, observational, spontaneous trial aimed to enhance the clinical action of THC: CBD cannabis extract administration in AD patients with severe symptoms such as agitation, weight loss, cognitive impairment, and sleep disturbance. Methods: Thirty patients (9 men and 21 women) diagnosed with mild, moderate, or severe AD, aged 65-90 years, appealing to our Second Opinion Medical Consultation (Modena, Italy), were enrolled and required to use oil-diluted cannabis extract, Bedrocan® (22% THC, 0.5% CBD, Olive Oil 50 ml), twice a day for 12 weeks. The efficacy of cannabinoid therapy was evaluated at baseline and 12 weeks after therapy, employing three self-administered questionnaires completed by the parents of the enrolled patients: NPI-Q, CMAI, and MMSE. Key findings: The NPI-Q demonstrated a reduction (p<0.0001) in agitation, apathy, irritability, sleep disturbances, and eating disturbances, consequently improving caregiver distress. Levels of physically and verbally aggressive behaviours, measured using the CMAI questionnaire, were lower (p<0.0001) in all patients. The MMSSE questionnaire confirmed a significant decrease (p<0.0001) in cognitive impairment in 45% of the patients. Conclusion: Our anecdotical, spontaneous, and observational study demonstrated the efficacy and safety of oil-diluted cannabis extract in patients with AD. The limitations of our study are: 1) small patient cohort, 2) absence of control group, 3) self-administered questionnaires that are the most practical but not objective instruments to assess the neurologic functions of AD patients.

Homeopatia: uma opção terapêutica na secura bucal em pacientes com doença de Alzheimer. Revisão de Literatura / Homeopathy: a therapeutic option for dry mouth in patients with Alzheimer´s disease. Literature Review

A homeopatia é uma especialidade odontológica, componente das práticas integrativas e complementares sendo regida pelo princípio da similaridade. Sua prática é geralmente utilizada no controle de doenças, sendo muito indicada naquelas que acometem os idosos de forma crônica, como a Doença de Alzheimer que pode causar a xerostomia (secura bucal) nos pacientes. O objetivo deste trabalho foi realizar uma revisão de literatura sobre a homeopatia como uma opção terapêutica na secura bucal em pacientes com Doença de Alzheimer. A Homeopatia pode atuar de forma interdisciplinar junto ao tratamento convencional não substituindo um pelo outro, sendo necessário uma anamnese minuciosa para coleta de sintomas, tornando imprescindível incluir manifestações mentais, gerais e locais na repertorização, individualizando-a ao máximo, já que a escolha do medicamento homeopático e o sucesso no tratamento está na dependência da totalidade dos sintomas com as suas modalidades. Entretanto como não há estudos suficientes que relacionam a homeopatia com a melhora da secura bucal em pacientes com Doença de Alzheimer, mais pesquisas são indicadas para comprovar a efetividade no tratamento.

Homeopathy is a dental specialty, a component of integrative and complementary practices, governed by the principle of similarity. Its practice is generally used in the control of diseases, being highly indicated in those that affect the elderly in a chronic way, such as Alzheimer's disease, which can cause xerostomia (dry mouth) in patients. The objective of this work was to carry out a literature review about homeopathy as a therapeutic option for dry mouth in patients with Alzheimer's disease. Homeopathy can act in an interdisciplinary way together with conventional treatment, not substituting one for the other, requiring a thorough anamnesis to collect symptoms, making it essential to include mental, general and local manifestations in the repertorization, individualizing it to the maximum, since the choice of the homeopathic medicine and the success of the treatment depends on the totality of the symptoms with their modalities. However, as there are not enough studies that relate homeopathy with the improvement of dry mouth in patients with Alzheimer's disease, more research is indicated to prove the effectiveness of the treatment

Promoted CD4+ T cell-derived IFN-γ/IL-10 by photobiomodulation therapy modulates neurogenesis to ameliorate cognitive deficits in APP/PS1 and 3xTg-AD mice.

BACKGROUND: The immune system has been implicated in synaptic plasticity, inflammation, and the progression of Alzheimer's disease (AD). However, there were few studies on improving the niche microenvironment of neural stem cells (NSCs) in the brain of AD to promote adult hippocampal neurogenesis (AHN) by regulating the function of non-parenchymal immune cells. METHODS: The lymph nodes of amyloid precursor protein/presenilin 1 (APP/PS1) and 3xTg (APP/PS1/tau) mouse models of AD were treated with photobiomodulation therapy (PBMT) for 10 J/cm2 per day for 1 month (10 min for each day), T lymphocytes isolated from these two AD models were treated with PBMT for 2 J/cm2 (5 min for each time). The NSCs isolated from hippocampus of these two AD models at E14, and the cells were co-cultivated with PBMT-treated T lymphocyte conditioned medium for NSCs differentiation. RESULTS: Our results showed that PBMT treatment could promote AHN and reverse cognitive deficits in AD mouse model. The expression of interferon-γ (IFN-γ) and interleukin-10 (IL-10) was upregulated in the brain of these two AD models after PBMT treated, which was induced by the activation of Janus kinase 2 (JAK2)-mediated signal transducer and activator of transcription 4 (STAT4)/STAT5 signaling pathway in CD4+ T cells. In addition, elevated CD4+ T cell levels and upregulated transforming growth factor-ß1 (TGFß1)/insulin-like growth factors-1 (IGF-1)/brain-derived neurotrophic factor (BDNF) protein expression levels were also detected in the brain. More importantly, co-cultivated the PBMT-treated T lymphocyte conditioned medium with NSCs derived from these two AD models was shown to promote NSCs differentiation, which was reflected in the upregulation of both neuronal class-III ß-tubulin (Tuj1) and postsynaptic density protein 95 (PSD95), but the effects of PBMT was blocked by reactive oxygen species (ROS) scavenger or JAK2 inhibitor. CONCLUSION: Our research suggests that PBMT exerts a beneficial neurogenesis modulatory effect through activating the JAK2/STAT4/STAT5 signaling pathway to promote the expression of IFN-γ/IL-10 in non-parenchymal CD4+ T cells, induction of improvement of brain microenvironmental conditions and alleviation of cognitive deficits in APP/PS1 and 3xTg-AD mouse models.

Beneficial Effects of Snail Helix aspersa Extract in an Experimental Model of Alzheimer's Type Dementia.

BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disease with multifactorial etiology, unsatisfactory treatment, and a necessity for broad-spectrum active substances for cure. The mucus from Helix aspersa snail is a mixture of bioactive molecules with antimicrobial, anti-inflammatory, antioxidant, and anti-apoptotic effects. So far there are no data concerning the capacity of snail extract (SE) to affect neurodegenerative disorders. OBJECTIVE: The effects of SE from Helix aspersa on learning and memory deficits in Alzheimer's type dementia (ATD) induced by scopolamine (Sco) in male Wistar rats were examined and some mechanisms of action underlying these effects were evaluated. METHODS: SE (0.5 mL/100 g) was applied orally through a food tube for 16 consecutive days: 5 days before and 11 days simultaneously with Sco (2 mg/kg, intraperitoneally). At the end of Sco treatment, using behavioral methods, we evaluated memory performance. Additionally, in cortex and hippocampus the acetylcholinesterase (AChE) activity, acetylcholine and monoamines (dopamine, noradrenaline, and serotonin) content, levels of main oxidative stress markers, and expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) were determined. RESULTS: We demonstrated that, according to all behavioral tests used, SE significantly improved the cognitive deficits induced by Sco. Furthermore, SE possessed AChE inhibitory activity, moderate antioxidant properties and the ability to modulate monoamines content in two brain structures. Moreover, multiple SE applications not only restored the depressed by Sco expression of CREB and BDNF, but significantly upregulated it. CONCLUSION: Summarizing results, we conclude that complex mechanisms underlie the beneficial effects of SE on impaired memory in Alzheimer's type dementia.

Co-Treatment with the Herbal Medicine SIP3 and Donepezil Improves Memory and Depression in the Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a lethal, progressive neurodegenerative disorder that has been linked to a deficiency of the neurotransmitter acetylcholine. Currently, many acetylcholinesterase inhibitors, such as donepezil, are widely used for the treatment of AD. On the other hand, the efficacy of long-term donepezil use is limited. SIP3, a mixture of three herbal extracts from Santalum album, Illicium verum, and Polygala tenuifolia, is a new formula derived from traditional Korean herbal medicine. OBJECTIVE: We assessed the synergistic effect of SIP3 and donepezil co-treatment on symptoms of AD using APP/PS1 transgenic mice. METHODS: In this study, a Drosophila AD model and SH-SY5Y clles were used to assess the toxicity of SIP3, and APPswe/PS1dE9 (APP/PS1) transgenic mice were used to evaluate the cognitive-behavioral and depression-like behavior effect of SIP3 and donepezil co-treatment on symptoms of AD. The cerebral cortex or hippocampus transcriptomes were analyzed by RNA sequencing and miRNA to investigate the molecular and cellular mechanisms underlying the positive effects of SIP3 on AD. RESULTS: In the passive avoidance test (PAT) and Morris water maze (MWM) test, the combination of SIP3 and donepezil improved the learning capabilities and memory of APP/PS1 mice in the mid-stage of AD compared to the group treated with donepezil only. In addition, co-administration of SIP3 and donepezil effectively reduced the depression-like behavior in the forced swimming and tail suspension tests. Furthermore, RNA sequencing of the cerebral cortex transcriptome and miRNA of the hippocampus showed that the gene expression profiles after a low dose SIP3 co-treatment were more similar to those of the normal phenotype mice than those obtained after the donepezil treatment alone. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, showed that differentially expressed genes were involved in the locomotor behavior and neuroactive ligand-receptor interactions. These results suggest that a co-treatment of low dose SIP3 and donepezil improves impaired learning, memory, and depression in the mid-stage of AD in mice. CONCLUSION: Co-treatment of low dose SIP3 and donepezil improves impaired learning, memory, and depression in the mid-stage of AD in mice.

The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: While Alzheimer's dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials. OBJECTIVE: The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric). METHODS: The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer's dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported). RESULTS: The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo. CONCLUSION: The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD.

Pseudobulbar affect in neurodegenerative diseases: A systematic review and meta-analysis.

BACKGROUND: Pseudobulbar affect (PBA) is characterized by uncontrolled episodes of crying and laughing which is associated with a variety of neurological diseases including traumatic brain injury, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), brain tumors, stroke, Parkinson's disease (PD), Alzheimer's disease (AD) and other dementias. However, there is a lack of exact estimated prevalence of PBA among neurological disorders. AIM: In this systematic review and meta-analysis study we aimed to assess the prevalence of PBA in four neurodegenerative diseases including ALS, MS, AD, and PD. METHODS: PubMed, Scopus, and Web of Science were searched in July 2021 for studies that reported the prevalence of PBA in ALS, MS, AD, and PD patients. The mean point of PBA prevalence and odds ratios were calculated as effect size (ES) using the random-effect model with a 95% confidence interval (CI). RESULTS: The summarized prevalence of PBA was of PBA in PD patients were ranged between 1% and 31% with an overall meta-analysis prevalence of 16.5% and high heterogeneity (I2: 98.7%, p: 0.000). Patients with ALS showed a PBA prevalence of 38.5%, which is higher than other neurodegenerative diseases (CI 95%: 31%-45%, I2: 61.4%, p: 0.034). Moreover, the prevalence of PBA in MS patients in the analysis was 23.3% ranging between 11% and 35% with high-level heterogeneity according to the I2 value (I2: 98.9%, p: 0.000). Also, our meta-analysis showed that the PBA prevalence in AD was 16.4% (CI 95%: 7%-25%) with high heterogeneity (I2: 97.8%, p: 0.000). CONCLUSION: This review showed that PBA is common in patients with neurodegenerative diseases including PD, AD, MS, and especially ALS. Due to the lack of proper recognition, medication and treatment would not be effective and sufficient. Therefore, it can dramatically lower the quality of life in PBA patients and decrease their social interactions.

Alzheimer's disease and related dementias and heart failure: A community study.

BACKGROUND: Cognitive function is essential to effective self-management of heart failure (HF). Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) can coexist with HF, but its exact prevalence and impact on health care utilization and death are not well defined. METHODS: Residents from 7 southeast Minnesota counties with a first-ever diagnosis code for HF between January 1, 2013 and December 31, 2018 were identified. Clinically diagnosed AD/ADRD was ascertained using the Centers for Medicare and Medicaid (CMS) Chronic Conditions Data Warehouse algorithm. Patients were followed through March 31, 2020. Cox and Andersen-Gill models were used to examine associations between AD/ADRD (before and after HF) and death and hospitalizations, respectively. RESULTS: Among 6336 patients with HF (mean age [SD] 75 years [14], 48% female), 644 (10%) carried a diagnosis of AD/ADRD at index HF diagnosis. The 3-year cumulative incidence of AD/ADRD after HF diagnosis was 17%. During follow-up (mean [SD] 3.2 [1.9] years), 2618 deaths and 15,475 hospitalizations occurred. After adjustment, patients with AD/ADRD before HF had nearly a 2.7 times increased risk of death, but no increased risk of hospitalization compared to those without AD/ADRD. When AD/ADRD was diagnosed after the index HF date, patients experienced a 3.7 times increased risk of death and a 73% increased risk of hospitalization compared to those who remain free of AD/ADRD. CONCLUSIONS: In a large, community cohort of patients with incident HF, the burden of AD/ADRD is quite high as more than one-fourth of patients with HF received a diagnosis of AD/ADRD either before or after HF diagnosis. AD/ADRD markedly increases the risk of adverse outcomes in HF underscoring the need for future studies focused on holistic approaches to improve outcomes.

Effect of light therapy on delirium in older patients with Alzheimer's disease-related dementia.

Light therapy has been used as a non-pharmacologic treatment to modulate biorhythms in patients with mental and psychological conditions. These conditions include affective disorders and depression. Delirium is a syndrome characterized by an acute change in a patient's mental status. We hypothesized that light therapy might suppress delirium in patients with Alzheimer's disease (AD). A 4-week randomized controlled trial was conducted in which AD participants were randomly assigned to a treatment group or a control group. Delirium, defined by the Confusion Assessment Method (CAM), was evaluated at baseline and after 4 weeks. The Neuropsychiatric Inventory (NPI) and Zarit Caregiver Burden Interview (ZBI) were also conducted to assess the behavior of patients and the burden of their caregivers. For this study, 61 participants were initially recruited. A total of 34 and 27 participants were included in the treatment and control groups, respectively. After treatment with light therapy, the CAM score decreased during the second and fourth week. The NPI score in the therapy group also decreased during the second and fourth week. From the caregiver's perspective, after light therapy, the ZBI score significantly decreased during the second and fourth week. Compared with the control group, patients who underwent CAM and NPI assessments showed a small but significant improvement after 4 weeks of light therapy. In conclusion, a course of 4-week light therapy significantly suppressed delirium in patients with AD. The combined effects of light therapy and conventional treatment were superior to that of conventional treatment alone.

Neurotoxic effects of aluminium exposure as a potential risk factor for Alzheimer's disease.

Aluminium is one of the most widely distributed elements of the Earth's crust. Its routine use has resulted in excessive human exposure and due to the potential neurotoxic effects has attained a huge interest in recent years. Despite its ubiquitous abundance, aluminium has no crucial biological functions in the human body. Oxidative stress and neuroinflammatory effects are attributed to its neurotoxic manifestations implicated in Alzheimer's disease. In this review, we have discussed the neuroinflammatory and neurodegenerative events in the brain induced by aluminium exposure. We have highlighted the neurotoxic events caused by aluminium, such as oxidative stress, apoptosis, inflammatory events, calcium dyshomeostasis, Aß deposition, and neurofibrillary tangle formation in the brain. In addition, the protective measures needed for prevention of aluminium-induced neuronal dysregulations have also been discussed.

[Sleep disorders in patients with a neurocognitive disorder]. / Les troubles du sommeil chez les patients atteints d'un trouble neurocognitif.

INTRODUCTION: Sleep disorders are prevalent in patients with a neurocognitive disorder, and diagnosis and treatment in these patients remain challenging in clinical practice. METHODS: This narrative review offers a systematic approach to diagnose and treat sleep disorders in neurocognitive disorders. RESULTS: Alzheimer's disease is often associated with circadian rhythm disorders, chronic insomnia, and sleep apnea-hypopnea syndrome. Alpha-synucleinopathies (e.g., Parkinson's disease and Lewy body dementia) are often associated with a rapid eye movement sleep behavior disorder, restless legs syndrome, chronic insomnia, and sleep apnea-hypopnea syndrome. A focused history allows to diagnose most sleep disorders. Clinicians should ensure to gather the following information in all patients with a neurocognitive disorder: (1) the presence of difficulties falling asleep or staying asleep, (2) the impact of sleep disturbances on daily functioning (fatigue, sleepiness and other daytime consequences), and (3) abnormal movements in sleep. Sleep diaries and questionnaires can assist clinicians in screening for specific sleep disorders. Polysomnography is recommended if a rapid eye movement sleep behavior disorder or a sleep apnea-hypopnea syndrome are suspected. Sleep complaints should prompt clinicians to ensure that comorbidities interfering with sleep are properly managed. The main treatment for moderate to severe obstructive sleep apnea-hypopnea syndrome remains continuous positive airway pressure, as its efficacy has been demonstrated in patients with neurocognitive disorders. Medications should also be reviewed, and time of administration should be optimized (diuretics and stimulating medications in the morning, sedating medications in the evening). Importantly, cholinesterase inhibitors (especially donepezil) may trigger insomnia. Switching to morning dosing or to an alternative drug may help. Cognitive-behavioral therapy for insomnia is indicated to treat chronic insomnia in neurocognitive disorders. False beliefs regarding sleep should be addressed with the patient and their caregiver. The sleep environment should be optimized (decrease light exposure at night, minimize noise, avoid taking vital signs, etc.). Sleep restriction can be considered as patients with a neurocognitive disorder often spend too much time in bed. The need for naps should be assessed case by case as naps may contribute to insomnia in some patients but allow others to complete their diurnal activities. Trazodone (50mg) may also be used under certain circumstances in chronic insomnia. Recent evidence does not support a role for exogenous melatonin in patients with a neucognitive disorder and insomnia. Patients in long-term care facilities are often deprived of an adequate diurnal exposure to light. Increasing daytime exposure to light may improve sleep and mood. Patients with circadian rhythm disorders can also benefit from light therapy (morning bright light therapy in case of phase delay and evening bright light therapy in case of phase advance). Rapid eye movement sleep behavior disorder can lead to violent behaviors, and the sleeping environment should be secured (e.g., mattress on the floor, remove surrounding objects). Medication exacerbating this disorder should be stopped if possible. High dose melatonin (6 to 18mg) or low dose clonazepam (0.125-0.25mg) at bedtime may be used to reduce symptoms. Melatonin is preferred in first-line as it is generally well tolerated with few side effects. Patients with restless legs syndrome should be investigated for iron deficiency. Medication decreasing dopaminergic activity should be reduced or stopped if possible. Behavioral strategies such as exercise and leg massages may be beneficial. Low-dose dopamine agonists (such as pramipexole 0.125mg two hours before bedtime) can be used to treat the condition, but a prolonged treatment may paradoxically worsen the symptoms. Alpha-2-delta calcium channel ligands can also be used while monitoring for the risk of falls. CONCLUSION: Multiple and sustained nonpharmacological approaches are recommended for the treatment of sleep disturbances in patients with neurocognitive disorder. Pharmacological indications remain limited, and further randomized clinical trials integrating a multimodal approach are warranted to evaluate the treatment of sleep disorders in specific neurocognitive disorders.

Analysis and Identification Genetic Effect of SARS-CoV-2 Infections to Alzheimer's Disease Patients by Integrated Bioinformatics.

BACKGROUND: COVID-19 pandemic is a global crisis which results in millions of deaths and causes long-term neurological sequelae, such as Alzheimer's disease (AD). OBJECTIVE: We aimed to explore the interaction between COVID-19 and AD by integrating bioinformatics to find the biomarkers which lead to AD occurrence and development with COVID-19 and provide early intervention. METHODS: The differential expressed genes (DEGs) were found by GSE147507 and GSE132903, respectively. The common genes between COVID-19 and AD were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPI) network analysis were carried out. Hub genes were found by cytoscape. A multivariate logistic regression model was constructed. NetworkAnalyst was used for the analysis of TF-gene interactions, TF-miRNA coregulatory network, and Protein-chemical Interactions. RESULTS: Forty common DEGs for AD and COVID-19 were found. GO and KEGG analysis indicated that the DEGs were enriched in the calcium signal pathway and other pathways. A PPI network was constructed, and 5 hub genes were identified (ITPR1, ITPR3, ITPKB, RAPGEF3, MFGE8). Four hub genes (ITPR1, ITPR3, ITPKB, RAPGEF3) which were considered as important factors in the development of AD that were affected by COVID-19 were shown by nomogram. Utilizing NetworkAnalyst, the interaction network of 4 hub genes and TF, miRNA, common AD risk genes, and known compounds is displayed, respectively. CONCLUSION: COVID-19 patients are at high risk of developing AD. Vaccination is required. Four hub genes can be considered as biomarkers for prediction and treatment of AD development caused by COVID-19. Compounds with neuroprotective effects can be used as adjuvant therapy for COVID-19 patients.