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Objectives: Many single nucleotide polymorphisms affect the incidence of Alzheimer’s disease (AD). This investigation aimed to consider the frequency of the C677T single nucleotide polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in Alzheimer’s patients. Materials and Methods: This study was conducted in two groups of control (n = 80) and patient (n = 80) with a ratio of 1: 1 male to female. Amplification-refractory mutation system-Polymerase Chain Reaction (ARMS-PCR) method was used to study mutations and ELISA was used to measure homocysteine and the chemiluminescence method was used to measure cholesterol, vitamin B12 and folate. Results: Based on the results of the PCR test of the MTHFR gene, the incidence rate of mutation in the healthy allele was 44.6% and in the mutant allele was 27.9% of the total study population. Conclusion: In this study, it was discovered that an increase in cholesterol levels is related with an increased risk of developing the disease, but more studies are needed to confirm this. It should also be noted that this increase is not related to the MTHFR gene polymorphism at the C677T position.

Abstract Background Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. Methods In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks. Results We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case–control gene expression studies suggests a female molecular predisposition towards Alzheimer’s disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. Conclusion Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences. Graphical Abstract

Background The prevalence of dementia in low- and middle-income countries is increasing, yet epidemiological data from African populations remain scarce. Crucial risk factors differ in Africa from more intensively studied global areas, including a high burden of cerebrovascular disease and HIV, but lower rates of other risk factors like physical inactivity. Understanding dementia aetiology in African settings has been limited by the expensive and invasive nature of biomarker testing. This study leverages developments in blood-based and retinal imaging biomarker technology to examine the drivers of dementia in older Ugandans. People with dementia have complex needs benefiting from multi-dimensional support. Understanding current services will allow identification of barriers and opportunities to strengthen support available to people with dementia and their families. Methods The study is nested within the existing General Population Cohort run by the MRC/UVRI & LSHTM Research Unit. Currently, all adults aged 60+ (around 1400) are undergoing brief cognitive screening. In Part 1, cohort participants will be selected based on cognitive screening scores to undergo detailed cognitive assessment, using methods developed by the 10/66 Dementia Research Group. Part 2 is a case control study of people with and without dementia using antecedent data, questionnaires, physical assessment, retinal imaging, and Alzheimer’s blood-based biomarkers. We will also compare disability, frailty, quality of life, and social engagement in people with and without dementia. Part 3 assesses current provision of formal support for people with dementia through review of publicly available literature and expert interviews. Conclusions This is the first study in Africa using blood-based and retinal imaging biomarkers to examine the pathological processes underlying dementia, and it will systematically map services available for people with dementia. This paves the way for effective policy strategies for both dementia prevention and support for people with dementia and their families.

Abstract Alzheimer’s disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach could be therapeutically beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) TgF344-AD rats, a transgenic Alzheimer’s model that exhibits age-dependent AD progression. We identified two potential early biomarker genes for AD, early growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of these two genes was significantly altered in 4-month TgF344-AD rats compared to wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial memory deficits and buildup of hippocampal Aβ plaques and tau PHF in 11-month TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this preclinical study is the first to report EGR2 and HIST1H2AA as potential AD biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations across multiple AD-related models is warranted to corroborate our findings.

The usefulness of Contingent Negative Variation (CNV) potential as a biomarker of neurocognitive disorders due to possible Alzheimer’s disease, is based on its possible physiological correlates. However, its application in the diagnostic evaluation of these disorders is still incipient. The aim of this study is to characterize the patterns of cognitive processing of information in the domain of nonspecific global attention, by recording potential CNV in a group of patients with neurocognitive disorders due to possible Alzheimer’s disease. An experimental study of cases and controls was carried out. The sample included 39 patients classified according to DSM-5 with a neurocognitive disorder subtype possibly due Alzheimer’s disease, and a Control Group of 53 subjects with normal cognitive functions. CNV potential was registered using standard protocol. The analysis of variance obtained significant differences in mean values and confidence intervals of total CNV amplitude between the three study groups. The late CNV segment amplitudes makes it possible to discriminate between the level of mild and major dysfunction in the group of patients. The CNV total amplitudes of potential allows for effective discrimination between normal cognitive functioning and neurocognitive disorders due to possible Alzheimer’s disease.

Objective(s): It is urgent to develop non-pharmacological interventions or multifactor combination approaches to combat Alzheimer’s disease (AD). The effect of exercise (EX) combined with environmental enrichment (EE) on behavioral phenotypes and neurogenesis markers in an Alzheimer-like rat model was investigated. Materials and Methods: The groups consisted of AD, sham-operated, AD+EX, AD+EE, and AD+EX+EE. AD was produced by injection of amyloid-beta (1-42, 6 µg) intrahippocampally, and a daily treadmill for 3 consecutive weeks was used for EX animals. EE was a large cage (50× 50× 50 cm) containing differently shaped objects. Spatial learning and memory were evaluated in the Morris water maze (MWM), and a shuttle box was used to evaluate inhibitory avoidance memory. RT-PCR was performed to assess the expression of early neurogenesis markers, DCX, and Sox2 within the hippocampus.Results: Pretreatment with exercise and EE, both individually and in combination, could provide protection from memory impairments in AD rats. Combined treatment led to a significantly more pronounced improvement in memory deficits of AD rats than either paradigm alone. Combination therapy with exercise and EE could also reverse the passive avoidance memory impairment and hippocampal DCX expression of AD rats to the control levels.Conclusion: These data suggest that exercise in combination with cognitive engagement can provide a non-pharmacological and multidomain policy that may prevent or delay AD symptoms.

Alzheimer’s disease (AD) is a neurodegenerative disease manifested with accumulation of neurotoxic proteins like beta-amyloid (Aβ) and hyperphosphorylated tau. Administration of angiotensin receptor blockers (ARBs) such as Telmisartan has demonstrated to generate significant memory improvement in AD. Azilsartan is an ARB with better bioavailability than Telmisartan. Hence, the present work evaluates the efficacy of Azilsartan against aluminium chloride (AlCl3) induced AD. In the work, albino rats were divided into five groups (n=6). Group I served as control and received saline (10 ml/kg). Group-II was treated with AlCl3 (100 mg/kg) for 42 days; Group-III and IV received Azilsartan (5 mg/kg) and Telmisartan (10 mg/kg) with AlCl3 daily for 42 days. Y-maze, elevated plus maze and radial arm maze were used to evaluate memory functions. This was followed by biochemical and histological studies, along-with determination of Aβ content and anti-oxidant status. AlCl3 was found to significantly (p

The escalating global healthcare challenge posed by Alzheimer’s Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D.

Background: This study evaluated the effects of zein nanoparticles with resveratrol on neuroinflammation caused by Alzheimer’s disease. Method: The sample consisted of 30 animals divided into control (C), positive control (CP), white nanoparticles (NB), resveratrol nanoparticles (NR) and resveratrol (R) groups. The animals received 10 mg/kg of resveratrol or nanoparticles according to the group, daily, for 15 days, oral administration. Afterward, they were submitted to immunohistochemical (IHC) analyses. Results: the IHC showed that there was no change in the morphological brain composition in the NR and C groups. Conversely, in the CP, NB, and R groups, changes in the deposition of Anti Tau were observed. The NR group showed a normal projection of taurine in the axon, which was not presented in the same way in the other groups. The CD68 marker showed no microglial activation in the R and C groups. Quantitative analyses of Anti Beta-Amyloid in the NR group showed a statistical difference compared to the CP, NB, and R groups, whereas the Anti Tau analysis showed a significant difference between the CP and NR groups. The CD68 marker showed a significant difference between the C and NR groups. The analysis of cytokines showed a significant difference in TNF-α between the C and CP groups, C and NB groups, CP and NR groups, and NB and NR groups. IL-6 and InF-δ showed no significant difference between all groups. IL-10 showed significant differences between the C and NR groups, C and R groups, and CP and NR groups. Conclusion: NR prevented the evolution of neuroinflammation.

Abstract Background The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia. Methods We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested. Results Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65–0.91; PYRAMID: HR = 0.86, 95% CI = 0.73–1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia. Conclusions Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

Natural visual experience involves a continuous series of related images while the subject is immobile. How does the cortico-hippocampal circuit process a visual episode? The hippocampus is crucial for episodic memory, but most rodent single unit studies require spatial exploration or active engagement. Hence, we investigated neural responses to a silent movie (Allen Brain Observatory) in head-fixed mice without any task or locomotion demands, or rewards. Surprisingly, a third (33%, 3379/10263) of hippocampal –dentate gyrus, CA3, CA1 and subiculum– neurons showed movie-selectivity, with elevated firing in specific movie sub-segments, termed movie-fields, similar to the vast majority of thalamo-cortical (LGN, V1, AM-PM) neurons (97%, 6554/6785). Movie-tuning remained intact in immobile or spontaneously running mice. Visual neurons had >5 movie-fields per cell, but only ~2 in hippocampus. The movie-field durations in all brain regions spanned an unprecedented 1000-fold range: from 0.02s to 20s, termed mega-scale coding. Yet, the total duration of all the movie-fields of a cell was comparable across neurons and brain regions. The hippocampal responses thus showed greater continuous-sequence encoding than visual areas, as evidenced by fewer and broader movie-fields than in visual areas. Consistently, repeated presentation of the movie images in a fixed, but scrambled sequence virtually abolished hippocampal but not visual-cortical selectivity. The preference for continuous, compared to scrambled sequence was eight-fold greater in hippocampal than visual areas, further supporting episodic-sequence encoding. Movies could thus provide a unified way to probe neural mechanisms of episodic information processing and memory, even in immobile subjects, across brain regions, and species.

A feasible system for measuring patient outcomes of rehabilitation is required for assessing the real-world cost-effectiveness of rehabilitation. This study aims to assess the feasibility of measuring outcomes of rehabilitation among elderly individuals with early-stage Alzheimer's. We used the principles of Design Science to construct a set of metrics consisting of standardized PROM (Patient-Reported Outcome Measure) questionnaires, clinician-reported measures, and observational measures of functioning. We used standardized questionnaires whenever possible to ensure the validity and reliability of the questionnaires. The set of metrics was piloted on 16 individuals living at home with regular home care services. After the pilot, we further refined the set of metrics based on relevance, sensitivity to change, and applicability. We found that measurement was feasible and we propose the final set of metrics as a minimum set, which could be further improved upon by addition of metrics relevant to each subgroup of elderly individuals. We also found that using self-reported questionnaires in this population is not without difficulties. We therefore suggest that the role of informal caregivers be considered, and that accessibility of outcome questionnaires be improved.

Alzheimer's disease is a common type of dementia. It is a progressive neurodegenerative disease that starts with mild memory loss and may progress to loss of ability to convey a conversation and respond to the surrounding. Early detection can help in the management of this disease. In this review, we attempted to find the most accurate method for salivary biomarkers detection, which can aid in the early diagnosis of Alzheimer's disease. For this scoping review; PubMed, Scopus, and Google Scholar online databases were searched to find studies and articles that test the salivary biomarkers for the diagnosis of Alzheimer's disease. Eleven studies were eligible for our research. Ten were case–control, and one was a cohort study. Seven of the studies used the enzyme-linked immunosorbent assay (ELISA) method, five of which showed diagnostic potential. Two studies used Luminex assay and photomultiplier tube, showing similar results to ELISA. AbsoluteIDQ®p150 Kit and faster ultra-performance liquid chromatography-mass spectrometry analysis and pattern recognition techniques tested different metabolites with potential diagnostic significance. Furthermore, another study using an extended gate ion sensitive field effect transistor sensor related salivary trehalose sugar to Alzheimer's disease. Different reliable biomarkers were detected using ELISA kit and appear to be effective in disease detection. Further studies and clinical trials on a large scale are required to determine the most accurate method of detecting Alzheimer's disease.

Abstract Unconventional protein secretion (UPS) is the new secretion process discovered in liquid form over three decades ago. More recently, UPS has been shown to operate also in solid forms generated from four types of organelles: fractions of lysosomes and autophagy (APh) undergoing exocytosis; exosomes and ectosomes, with their extracellular vesicles (EVs). Recently many mechanisms and proteins of these solid forms have been shown to depend on UPS. An additional function of UPS is the regulation of diseases, often investigated separately from each other. In the present review, upon short presentation of UPS in healthy cells and organs, interest is focused on the mechanisms and development of diseases. The first reported are neurodegenerations, characterized by distinct properties. Additional diseases, including inflammasomes, inflammatory responses, glial effects and other diseases of various origin, are governed by proteins generated, directly or alternatively, by UPS. The diseases most intensely affected by UPS are various types of cancer, activated in most important processes: growth, proliferation and invasion, relapse, metastatic colonization, vascular leakiness, immunomodulation, chemoresistence. The therapy role of UPS diseases depends largely on exosomes. In addition to affecting neurodegenerative diseases, its special aim is the increased protection against cancer. Its immense relevance is due to intrinsic features, including low immunogenicity, biocompatibility, stability, and crossing of biological barriers. Exosomes, loaded with factors for pharmacological actions and target cell sensitivity, induce protection against various specific cancers. Further expansion of disease therapies is expected in the near future.

Background and Objective: In this study, the thickness of the retinal nerve fibers layer(RNFL) was compared among patients with mild cognitive impairment, Alzheimer's dementia, and healthy individuals (controls) using Optical Coherence Tomography (OCT) device. Materials and Methods: This case-control study was conducted on 30 patients diagnosed with mild cognitive impairment and 31 healthy subjects undergoing neurological examination. The examinations included minimal mental state examination a comprehensive assessment of ophthalmology and performance of OCT using a Spectralis device. Both eyes were selected for analysis, and the differences in the thickness of retinal nerve fibers layer between patients with mild cognitive impairment and healthy subjects were investigated. Results: In this study, the mean age scores of the patients and healthy individuals were 66.00±8.56 and 60.25±7.50 years, respectively. According to the results of the ordinal logistic regression model, after controlling the effects of other variables, the severity of cognitive impairment increased by 1.26 times in the right eye and by 1.30 times in the left eye (P

Alzheimer’s disease is the sixth most common cause of death in the United States (U.S.), with one in three adults 65 years of age and older dying of the disease each year. Deaths from Alzheimer’s have more than doubled between 2000 and 2019, killing more adults than both breast cancer and prostate cancer. In 2021, Alzheimer’s disease resulted in 36 deaths per 100,000 in the U.S. In Mississippi, deaths from Alzheimer’s have almost doubled between 2011 and 2021, resulting in 52.9 deaths per 100,000. Women have a higher mortality rate from Alzheimer’s than men. Alzheimer’s is a progressive disease that develops through seven stages. There are effective strategies to prevent the onset of Alzheimer’s. Methods: This paper reviews the risk factors, mortality trends, etiology, and prognosis of Alzheimer’s in Mississippi with a focus on prevention. Results: The southern diet with foods high in sugar and sodium, along with sedentary and poor lifestyle choices, increases mortality risk from Alzheimer’s disease for women in Mississippi, specifically due to women over 65 having higher rates of obesity and hypertension. Conclusion: Understanding the epidemiology and risk factors of Alzheimer’s in Mississippi will help inform communities, policies, and programs to prevent disease occurrence.

Background: Activation of brain renin angiotensin system is associated with neurodegenerative disorders like Alzheimer's disease (AD). AD is the most common type of dementia. Angiotensin Receptor Blockers (ARBs) like Telmisartan, Azilsartan, Valsartan and Losartan have shown efficacy against animal models of AD. The efficacy of Irbesartan in AD has not been thoroughly investigated. Aluminium chloride (AlCl ) induces AD like pathology in rats. Aim and Objectives: The present work evaluates the efficacy of Irbesartan against AlCl induced amyloidogenesis and cognitive impairment. Material and Methods: Wistar albino rats were divided into four groups containing six each. Group I (saline 10 ml/kg p.o.) and Group II (AlCl 100 mg/kg p.o.) served as normal control and toxic control respectively. Both the groups were dosed daily for 42 days. Group III and Group IV received Irbesartan (10 mg/kg) and Telmisartan (10 mg/kg) respectively with AlCl daily for 42 days. The drugs were given 1 hour before the administration of AlCl . Y-maze, elevated plus maze and radial arm maze were used to evaluate memory functions on day 0 and 42. Amyloid β (Aβ) content and enzymatic anti-oxidant status in both plasma and brain homogenate were measured and histological studies of brain tissues were done on day 43. Results: AlCl (100 mg/kg, p.o.) significantly (p

Background: Alzheimer's disease (AD) is a neurodegenerative disorder marked by brain inflammation resulted in structural damage and brain dysfunction. Tumor necrosis factor α (TNFα) is a cytokine that plays an important role in inflammation. Dates fruit may help to fight oxidative stress and inflammation in the brain. Objective: To determine the effect of date fruit extracts on blood TNFα levels and brain weight of alzheimer’s model rats. Methods: This research is a laboratory experimental study by post-test only with control group design using alzheimer model rats. This study used 6 treatment groups with simple randomization. Each treatment group was represented by 8 Sprague Dawley rats. The normal control group (KN) was not induced by Hcy and was not given date palm extract, the negative control group (K-) was the Alzheimer's experimental rats which was not given the date palm extract, the positive group was the Alzheimer's experimental rats which was given the Donepezil (K+). Groups P1, P2, P3 were Alzheimer's experimental rats that were given date palm extract at a dose of 200, 400,800 mg / kgBW / day. The effect of date palm extract dosage on TNFα levels and brain weight were analyzed using the One Way Anova test followed by Tukey's post hoc test. Results: The difference in TNFα levels between groups showed a significant difference (p = 0.00). Meanwhile there was no significant difference in brain weight among all groups (p > 0,05). Conclusion: Date palm extract at doses of 200, 400, 800 mg / kgBW can decrease blood TNFα levels of Alzheimer’s model rats.

Amyotrophic lateral sclerosis (ALS) is classified as a motor neuron disease (MND) that can present with both upper and lower motor neuron signs. Concurrent ALS and frontotemporal dementia (FTD) is also a well-known phenomenon. Examples of other primary disorders mimicking ALS or ALS-FTD have been reported in the literature and recognition of these entities is important to ensure proper clinical management. We present here an unusual case of an 86-year-old male patient, clinically diagnosed with ALS and severe cognitive impairment thought to be due to FTD. Postmortem neuropathological examination of his brain and spinal cord did not reveal the typical findings of ALS or FTD. Rather, it revealed multiple non-ALS pathologies including argyrophilic grain disease (AGD), cerebrovascular disease, and Alzheimer’s type pathology. This case raises the possibility that mixed pathologies could mimic motor neuron disease.

Alzheimer's disease is one of the problems that usually affects the elderly and causes memory problems. In order to determine the appropriate method of Alzheimer's treatment, first this complication must be accurately diagnosed. To diagnose this condition, the doctor uses various tests to rule out the possibility of other diseases. In this study, the ways of diagnosing the disease such as MRI and other methods are described and the methods of Alzheimer's treatment (pharmacological and non-pharmacological) are reviewed. In this study, by examining 121 samples of patients with Alzheimer's, recommendations have been made regarding the care of Alzheimer's patients. The results showed that memory loss is the first sign of Alzheimer's. Usually, a person with memory problems does not notice the occurrence of this problem, and friends and family members find out about this problem. The occurrence of problems in short-term memory is common in the sixth and seventh decades of life; But it does not mean the occurrence of Alzheimer's. Normal memory problems are different from the type of memory problems caused by Alzheimer's. [ABSTRACT FROM AUTHOR]

INTRODUCTION The development of PET radiopharmaceuticals suitable for the identification and in vivo quantification of β Amyloid plaques has been the focus of intense research, representing a useful means for the non-invasive detection of β Amyloid plaques in subjects affected by the Alzheimer's disease (AD). The purpose of this article is to provide a general overview of the application of PET radiopharmaceuticals currently available for in vivo imaging of β amyloid plaques. The aim is therefore to describe the chemical and synthetic characteristics of the main radiopharmaceuticals currently used in in vivo amyloid imaging and to provide a technical description of the acquisition protocols, always keeping the patient at the center of each step. MATERIALS AND METHODS Radiopharmaceuticals for PET imaging of amyloid β include two broad classes: planar hetero aromatic compounds and alkenes analogs. Among the former are 11C PiB and 18F Flutemetmol. While among the analogues of alkenes, the most used are the following two radiolabelled compounds: [18F] Florbetaben; [18F] AV-45, Florpyramine, [18F] Florbetapir. A suitable and standardized protocol depending on the radiopharmaceutical used together with technical precautions and good communication with the client, contribute to the good quality of the service offered, both in terms of efficacy and safety of the treatments. It is important to have a professional attitude aimed at active listening, to formulate short, precise sentences, composed of simple and clear words, to speak slowly and to give time to respond. The patient with demented syndrome needs a relaxed and non-judgmental environment. Current PET / CT on the market are equipped with tools such as automatic exposure control and iterative algorithms, useful for reducing and optimizing the radiation exposure, the scan parameters may vary depending on the type of scanner. In clinical practice it is commonly used to use 120 KV and 60-100 mA, to obtain a suitable attenuation map and morphological localization. The PET scan is reconstructed using a 256 × 256 matrix using an iterative algorithm with a Gaussian low-pass filter. Both PET and CT data are constructed with a 25-30cm FOV. CONCLUSIONS The radiopharmaceuticals currently available must be known for their respective specifications by the technologist, in order to guarantee the correct acquisition and compliance with the exam timing. An adequate implementation of technical skills and soft communication skills makes an appropriate context for the delicate balance of AD patients, having the patients and their specific needs at the center of health care.

Background: In recent years, the potential role of probiotics has become prominent in the discoveries of neurotherapy against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Lactic acid bacteria (LAB) exhibit neuroprotective properties and exert their effects via various mechanisms of actions. This review aimed to evaluate the effects of LAB on neuroprotection reported in the literature. Methods: A database search on Google Scholar, PubMed, and Science Direct revealed a total of 467 references, of which 25 were included in this review based on inclusion criteria which comprises 7 in vitro, 16 in vivo, and 2 clinical studies. Results: From the studies, LAB treatment alone or in probiotics formulations demonstrated significant neuroprotective activities. In animals and humans, LAB probiotics supplementation has improved memory and cognitive performance mainly via antioxidant and anti-inflammatory pathways. Conclusions: Despite promising findings, due to limited studies available in the literature, further studies still need to be explored regarding synergistic effects, efficacy, and optimum dosage of LAB oral bacteriotherapy as treatment or prevention against neurodegenerative diseases.

Older adults living with dementia experience progressive decline, prompting reliance on others for spiritual care and support. Despite a growing interest in studying persons living with dementia (PLwDs), empirical evidence on the spiritual needs of PLwDs has not been synthesized. Using the Whittemore and Knafl method, this integrative review examined the literature from 2000 to 2022 on the spiritual care needs of PLwDs. We sought to identify characteristics of the spiritual needs of PLwDs and ways to address them. The ATLA Religion, CINAHL, PsycINFO, PubMed, and Socindex databases were used to search the literature, and 12 peer-reviewed articles met the inclusion criteria. Spiritual care needs varied across studies. Overall, findings support the importance of identifying PLwDs’ religious and spiritual backgrounds to inform person-centered care. Spiritual needs were identified as verbal and non-verbal expressions related to past meaning and religious and spiritual background and were not consistently addressed in care. Providers reported observing spiritual distress in the mild stage prompting the need for spiritual care. There is a great need for dementia-specific spiritual assessment tools and spiritual care interventions to support spiritual well-being in dementia care. Spiritual care involves facilitating religious rituals and providing spiritual group therapy and religious and spiritual activities.

Background: Alzheimer’s disease and related dementias (ADRDs) pose a major public health challenge in older adults. In sub-Saharan Africa, the burden of ADRD is projected to escalate amidst ill-equipped healthcare workers (HCWs). Aim: This study aimed to assess ADRD knowledge amongst Ghanaian HCWs and improve gaps identified through a workshop. Setting: Study was conducted among HCWs attending a workshop in Kumasi, Ghana. Methods: On 18 August 2021, a workshop on ADRD was organised in Kumasi, Ghana, which was attended by 49 HCWs comprising doctors, nurses, pharmacists, social workers and nutritionists. On arrival, they answered 30 pre-test questions using the Alzheimer’s Disease Knowledge Scale (ADKS). A post-test using the same questionnaire was conducted after participants had been exposed to a 4-h in-person educational content on ADRD delivered by facilitators from family medicine, neurology, geriatrics, psychiatry and public health. Results: The mean age of participants was 34.6 (± 6.82), mean years of practice was 7.7 (± 5.6) and 38.8% (n = 19) were nurses. The mean score of participants’ overall knowledge was 19.8 (± 4.3) at pre-test and 23.2 (± 4.0) at post-test. Participants’ pre-test and post-test scores improved in all ADKS domains. Factors associated with participants’ knowledge at baseline were profession, professional rank and the highest level of education attained. After adjusting for age and sex, participant’s rank, being a specialist (adjusted β = 14.44; 95% confidence interval [CI] = 7.03, 21.85; p 0.001) was an independent predictor of knowledge on Alzheimer’s disease. Conclusion: Existing knowledge gaps in ADRD could be improved via continuous medical education interventions of HCWs to prepare healthcare systems in Africa for the predicted ADRD epidemic.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. To date, therapies targeting end-stage disease plaques, tangles, or inflammation have limited efficacy. Therefore, we set out to identify a potential earlier targetable phenotype. Utilizing a mouse model of AD and human fetal cells harboring mutant amyloid precursor protein, we show cell intrinsic neural precursor cell (NPC) dysfunction precedes widespread inflammation and amyloid plaque pathology, making it the earliest defect in the evolution of the disease. We demonstrate that reversing impaired NPC self-renewal via genetic reduction of USP16, a histone modifier and critical physiological antagonist of the Polycomb Repressor Complex 1, can prevent downstream cognitive defects and decrease astrogliosis in vivo. Reduction of USP16 led to decreased expression of senescence gene Cdkn2a and mitigated aberrant regulation of the Bone Morphogenetic Signaling (BMP) pathway, a previously unknown function of USP16. Thus, we reveal USP16 as a novel target in an AD model that can both ameliorate the NPC defect and rescue memory and learning through its regulation of both Cdkn2a and BMP signaling.

Background: Approximately 50 million people worldwide are suffering from dementia, it is the 7th leading cause of death among the elderly. In India, more than 4 million people have some form of dementia 3. According to the World Health Organization, India’s population of those aged over 65, which was 40 million in 1997, is set to increase to 108 million by 2025 and 240 million by 2050. Aim and Objective: The aim of the study was to study the prevalence of risk factors of dementia among the elderly population residing in a tribal area of Central India. Materials and Methods: A door to door cross-sectional study was conducted in the rural/tribal area with a pre-designed case record form that investigated the prevalence of risk factors along with measurement of anthropometry and mini-mental state examination was used to categorize subjects according to their mental status. Results: This study reports high prevalence of risk factors such as hypertension (31.8%), tobacco chewing (25.43%), high waist-hip ratio (24.57%), smoking habit (15.03%), head injury (11%), overweight (9.54%), alcohol intake (9.25%), 71–80 age (9.25%), diabetics (9%), stroke (4.62%), family history of dementia (2.6%), obesity (2.31%), coronary artery disease (CAD) (1.73%), and depression (1.45%). Conclusions: This study highlights a significant burden of undiagnosed cases of hypertension, diabetes, depression, and CAD all of which are important risk factors for dementia in the community, most of them are poorly controlled. There is a need to identify the large pool of undiagnosed cases of the mentioned morbidities by screening and offer early treatment to avoid complications.

Objective (s): Caring for elderly with Alzheimer can lead to the development or exacerbation of many physical and psychological problems for caregivers. The purpose of this study was to assess the anxiety and depression in caregivers of elderly with Alzheimer. Methods: This was a cross-sectional study of 315 caregivers of elderly people with Alzheimer in Tehran, Iran. Data were collected by demographic questionnaire, the Beck Anxiety Inventory and the Beck Depression Inventory. Descriptive statistics were used for data analysis. Results: The mean and standard deviation of caregivers’ anxiety was 12.61± 10.48 which was significantly higher in women than men (p = 0.004). The mean and standard deviation of caregivers’ depression was 13.23 ± 9.52 which was significantly higher in women than men (p = 0.001). The results of t-test and one-way analysis of variance showed that there was a significant difference between total anxiety score by gender, caregiver-to-elderly ratio, health status and caregivers’ income status (p = 0.001). There was also a significant difference between the overall score of depression and marital status, gender, income and caregivers health status (p = 0.001). Conclusion: The study showed that Alzheimerchr('39')s caregivers experience mild to moderate levels of anxiety and depression. The findings suggest strategic planning to increase social support among Alzheimerchr('39')s caregivers is essential.

The One Card Learning Test (OCL80) from the Cogstate Brief Battery—a digital cognitive test used both in-person and remotely in clinical trials and in healthcare contexts to inform health decisions—has shown high sensitivity to changes in memory in early Alzheimer's disease (AD). However, recent studies suggest that OCL sensitivity to memory impairment in symptomatic AD is not as strong as that for other standardized assessments of memory. This study aimed to improve the sensitivity of the OCL80 to AD-related memory impairment by reducing the test difficultly (i.e., OCL48). Experiment 1 showed performance in healthy adults improved on the OCL48 while the pattern separation operations that constrain performance on the OCL80 were retained. Experiment 2 showed repeated administration of the OCL48 at short retest intervals did not induce ceiling or practice effects. Experiment 3 showed that the sensitivity of the OCL48 to AD-related memory impairment (Glass's Δ = 3.11) was much greater than the sensitivity of the OCL80 (Glass's Δ = 1.94). Experiment 4 used data from a large group of cognitively normal older adults to calibrate performance scores between the OCL80 and OCL48 using equipercentile equating. Together these results showed the OCL48 to be a valid and reliable test of learning with greater sensitivity to memory impairment in AD than the OCL80.

Apolipoprotein E4 (ApoE4) is the most important and prevalent risk factor for late-onset Alzheimer’s disease (AD). The isoelectric point of ApoE4 matches the pH of the early endosome (EE), causing its delayed dissociation from ApoE receptors and hence impaired endolysosomal trafficking, disruption of synaptic homeostasis, and reduced amyloid clearance. We have shown that enhancing endosomal acidification by inhibiting the EE-specific sodium-hydrogen exchanger 6 (NHE6) restores vesicular trafficking and normalizes synaptic homeostasis. Remarkably and unexpectedly, loss of NHE6 (encoded by the gene Slc9a6) in mice effectively suppressed amyloid deposition even in the absence of ApoE4, suggesting that accelerated acidification of EEs caused by the absence of NHE6 occludes the effect of ApoE on amyloid plaque formation. NHE6 suppression or inhibition may thus be a universal, ApoE-independent approach to prevent amyloid buildup in the brain. These findings suggest a novel therapeutic approach for the prevention of AD by which partial NHE6 inhibition reverses the ApoE4-induced endolysosomal trafficking defect and reduces plaque load.

Abstract Background With increasing numbers of people in the UK living with dementia, the provision of good quality person-centred care that meets the often complex needs of this population is required. Given the majority of people with dementia live in the community, significant care and support will be provided by primary care services. This means the primary care workforce needs appropriate education to ensure they have the right knowledge, skills and attitudes to meet these care needs. However, little is understood about the most successful approaches to dementia education in this setting. Methods An in-depth case study was undertaken in a single primary care organisation with the aim of exploring the impact of a person-centred dementia educational programme, and identify barriers and facilitators to implementation. Data was gathered from a wide range of sources and analysed using Kirkpatrick’s evaluative framework. Results Initially, staff learners struggled to incorporate the ‘whole-person’ approach to dementia care, but gained knowledge and confidence through self-directed learning. They reacted positively to the training and appreciated opportunities to learn from peers in other services. They identified improvements in communication and prescribing practices, despite difficulties implementing changes during busy periods. Resultant impact for service users included more timely routine appointments, and positive satisfaction ratings from patients and families. Conclusions The findings indicate the perceived value of person-centred dementia education for primary care. Further recommendations for provision in this service setting include tailored programmes designed collaboratively with clinical service providers, and bringing together an interdisciplinary mix of learners to enhance knowledge exchange.

Abstract Background People with dementia (PwD) vary in the degree of awareness they show about their situation, both generally concerning the diagnosis and more specifically around certain aspects or objects of awareness such as awareness of memory impairment, altered daily activities or social functioning. The extent of awareness or lack of awareness has consequences for well-being of PwD and carers, impacting on rates of hospital admission, institutionalization, mood, adjustment to diagnosis, outcomes from intervention and carer burden. An accurate estimation of a person’s awareness could therefore be useful in a clinical setting to support PwD and their carers in making appropriate choices for health and care decisions, and could facilitate safe management by health care professionals, e.g. in an acute care setting. There is a range of different approaches to measuring awareness reported in the dementia research literature, with varying estimates of the frequency of lack of awareness, reflecting different methodologies and populations. The majority of the methods have been developed for research purposes and may not be suitable for clinical use. There are no recent scoping or systematic reviews of the available methods. Method We will conduct a scoping review of published studies that have assessed awareness in people with dementia of all types, and all degrees of severity. The systematic search will include the electronic databases PubMed, Embase, PsycInfo, CINAHL, Web of Science and Cochrane Library, using search terms for dementia (“dement*” or “Alzheimer*” or “Pick’s disease”) and “awareness”, “unawareness”, “anosognosia”, “insight”, “denial”, “metacognit*” or “discrepanc*” identified from pilot searches. Findings will be mapped and described according to the method used, the setting and diagnosis and the object of awareness studied if specified. Validated measures will be identified. Discussion This scoping review will provide an overview of the methods used to measure awareness in people with dementia, allowing comparison of the methods along with identification of validated measures. The methods or components will be appraised for potential clinical use, and gaps in research will be highlighted.

An approach called deep mutational scanning is improving our understanding of amyloid beta aggregation.

Plaques of the amyloid beta (Aß) peptide are a pathological hallmark of Alzheimer’s disease (AD), the most common form of dementia. Mutations in Aß also cause familial forms of AD (fAD). Here, we use deep mutational scanning to quantify the effects of >14,000 mutations on the aggregation of Aß. The resulting genetic landscape reveals mechanistic insights into fibril nucleation, including the importance of charge and gatekeeper residues in the disordered region outside of the amyloid core in preventing nucleation. Strikingly, unlike computational predictors and previous measurements, the empirical nucleation scores accurately identify all known dominant fAD mutations in Aß, genetically validating that the mechanism of nucleation in a cell-based assay is likely to be very similar to the mechanism that causes the human disease. These results provide the first comprehensive atlas of how mutations alter the formation of any amyloid fibril and a resource for the interpretation of genetic variation in Aß.

In Prion Diseases, misfolding of neuronal prion protein (PrPC) to a pathogenic isomer (PrPSC) is associated with neuronal death. Previous pathological studies have demonstrated increased immunoreactivity of PrPC at Aβ plaques in Alzheimer's Disease, and it has been suggested that this either reflects a role for PrPC in the neuronal response to stress or is a feature of the neuropathogenesis of atypical subtypes of Alzheimer's disease. In this paper we utilised western blotting to examine the molecular characteristics of PrP in frozen Hippocampal tissue from 7 cases of Alzheimer's Disease in which prion protein expression was demonstrated by immunohistochemistry, before using Restriction Fragment Length Polymorphism (RFLP) methodology to define the genotype of the codon 129 polymorphism of PRNP in each case. We observed PrP accumulating as globular structures at A plaques, and within ependymal cells lining the lateral ventricle. Immunohistochemistry also showed that PrPC and Superoxide dismutase-1 where deposited in a similar pattern at Aβ plaques. Western blotting revealed that PrP in Alzheimer's disease is composed of the same 208-residue peptide expressed in non-diseased brain. Quantitative western blot analysis demonstrated increased levels of PrPC in a short duration case of Alzheimer's Disease, while, in the remaining cases, levels of PrPC decreased in parallel with increasing disease duration and decreasing brain mass. RFLP genotyping revealed that all codon 129 genotypes (M/M, M/V, V/V) were represented in our study cohort. Our data suggest that increased levels of PrPC may account for PrP immunoreactivity at plaques in Alzheimer's disease, and that PrP deposition is not restricted to certain atypical subtypes of Alzheimer's disease.

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Alzheimer’s disease and vascular dementia account for the majority of cases of cognitive decline in elderly people. These two main forms of dementia, under which various subtypes fall, are often overlapping and, in some cases, definitive diagnosis may only be possible post-mortem. This has implications for the quality of care and the design of individualized interventions for these patients. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality used to visualize the retinal layers and vessels which shows encouraging results in the study of various neurological conditions, including dementia. This review aims to succinctly sum up the present state of knowledge and provide critical insight into emerging patterns of OCTA biomarker values in Alzheimer’s disease and vascular dementia. According to the current literature, vessel density seems to be a common biomarker for both forms; inner retinal layer thickness might represent a biomarker preferentially affected in degenerative dementia including Alzheimer’s, while, in contrast, the outer-layer thickness as a whole justifies attention as a potential vascular dementia biomarker. Radial peripapillary capillary density should also be further studied as a biomarker specifically linked to vascular dementia.

Saporin is a ribosome-inactivating protein that can cause inhibition of protein synthesis and causes cell death when delivered inside a cell. Development of commercial Saporin results in a technology termed ‘molecular surgery’, with Saporin as the scalpel. Its low toxicity (it has no efficient method of cell entry) and sturdy structure make Saporin a safe and simple molecule for many purposes. The most popular applications use experimental molecules that deliver Saporin via an add-on targeting molecule. These add-ons come in several forms: peptides, protein ligands, antibodies, even DNA fragments that mimic cell-binding ligands. Cells that do not express the targeted cell surface marker will not be affected. This review will highlight some newer efforts and discuss significant and unexpected impacts on science that molecular surgery has yielded over the last almost four decades. There are remarkable changes in fields such as the Neurosciences with models for Alzheimer’s Disease and epilepsy, and game-changing effects in the study of pain and itch. Many other uses are also discussed to record the wide-reaching impact of Saporin in research and drug development.

Background: Recently, we reported that patients with mild cognitive impairment (MCI) harbor specific signature of bacteria in their gut and that a modified Mediterranean ketogenic diet (MMKD) improves Alzheimer's disease (AD) markers in cerebrospinal fluid (CSF) and the signatures of gut bacteria. However, other microbial population such as gut fungi (mycobiome) in relation to MCI/AD pathology, gut bacteria and diet remain unknown. Methods: We measure gut mycobiome by sequencing of the fungal rRNA ITS1 gene in 17 older adults (11 MCI; 6 cognitively normal [CN]) in a single-center, randomized, double-blind, crossover pilot study, before and after 6 weeks intervention of MMKD and American Heart Association Diet (AHAD), and determine its correlation with AD markers in CSF and gut bacteria. Findings: Compared to CN counterparts, patients with MCI have higher proportion of families Sclerotiniaceae, Phaffomyceteceae, Trichocomaceae, Cystofilobasidiaceae, Togniniaceae and genera Botrytis, Kazachstania, Phaeoacremonium and Cladosporium and lower abundance of Meyerozyma. Specific fungal taxa exhibit distinct correlation arrays with AD markers and gut bacteria in subjects with versus without MCI. MMKD induces broader effect on fungal diversity in subjects with MCI and increases Agaricus and Mrakia while decreasing Saccharomyces and Claviceps with differential response in subjects with or without MCI. Interpretation: The study reveals MCI-specific mycobiome signatures and demonstrates that distinct diets modulate the mycobiome in association with AD markers and fungal-bacterial co-regulation networks in patients with MCI. The findings corroborate the notion of considering gut mycobiome as a unique factor that can affect cognitive health/AD by interacting with gut bacteria and diet and facilitate better understanding of the AD and related microbiome, using unique diet or microbiome modulators.

Whether and how persistent firing in lateral entorhinal cortex layer III (LEC III) supports temporal associative learning is still unknown. In this study, persistent firing was evoked in vitro from LEC III neurons from young and aged rats that were behaviorally naive or trained on trace eyeblink conditioning. Persistent firing ability from neurons from behaviorally naive aged rats was lower compared to neurons from young rats. Neurons from learning impaired aged animals also exhibited reduced persistent firing capacity, which may contribute to aging-related learning impairments. Successful acquisition of the trace eyeblink task, however, increased persistent firing ability in both young and aged rats. These changes in persistent firing ability are due to changes to the afterdepolarization, which may in turn be modulated by the postburst afterhyperpolarization. Together, these data indicate that successful learning increases persistent firing ability and decreases in persistent firing ability contribute to learning impairments in aging.

Aim - research of gene APOE for definition of allele structures of the human population phenotypes resulting in risk of Alzheimer’s disease. Materials and methods. Use of the Hardy-Weinberg theory and statistical researches of the alleles distribution of gene APOE in a human population. Results. Principles of the phenotype allele structures formation resulting in risk of Alzheimer’s disease are investigated. The expediency of these phenotypes finding is shown. On the basis of the received phenotypes distribution in human population the dependence of phenotype frequencies on risk of Alzheimer’s disease is investigated. The most dangerous phenotypes are revealed. Conclusion. On the basis of representation about dominant and recessive structure of gene APOE alleles it is shown that in a human population exists three phenotypes which determine the risk of Alzheimer’s disease. Distribution of these phenotypes in populations is investigated.

Aim: To determine the perceived needs of carers of non-institutionalized family members that suffer from dementia. Methods: Two-steps qualitative study by focus groups of relatives in three centres of different characteristics from the Girona Health Region (step 1) and two in-depth interviews with significant professionals in dementia care (step 2). The analysis was performed based on the interpretation of the transcribed data and the bottom-up coding of categories and themes. The information was triangulated and coding was agreed upon. Results: There were three groups, 26 main carers of community-dwelling relatives with dementia in step 1 and two in-depth interviews with dementia-specialised healthcare and social care professionals in step 2. The demands were categorised according to three main themes: whether they were addressed to the members of care services for more direct and close care, to the agencies for a better joint working and less fragmented system, or to society for better comprehension and social recognition. We emphasize the need for a consultation-liaison reference figure throughout the process both for aspects of greater efficiency in the management of resources and for greater empowerment of carers.

Dementia is a general term for a series of medical conditions that affect the brain and evolve progressively. According to the literature, there are over 200 subtypes and causes of dementia, with Alzheimer’s disease (AD) being the most common in elderly people. AD is an irreversible progressive neurodegenerative condition that leads to a decline in mental function, enough to disrupt daily life. Thinking skills slowly deteriorate, which, in advanced stages, makes it impossible to perform simple tasks. Besides the change in the quality of life of AD patients and their families, there is a considerable alteration in the quality of life of their caregivers, whose health can be negatively affected by the development of mental and somatic disorders. This article reviews the literature in order to reveal the benefits of applying non-pharmacological interventions such as music and art therapy to improve quality of life. This article also aims to shed light on the impact of this disease on the caregiver’s life. Music and art therapy have produced reliable results in the treatment of patients with AD, and the best effects are related to increased socialization and the maintenance of social status.

HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11β1/2 genes in adults. A total of 32 studies were identified. There is prospective evidence for an association between HSD11β2 methylation and hypertension, and functional evidence of an association between NR3C1 methylation and both small cell lung cancer (SCLC) and breast cancer. Strong associations have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically-plausible associations have been reported between FKBP5 methylation and Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental health outcomes have been reported according to different social and environmental exposures, and according to varying gene regions investigated. We conclude by highlighting key challenges and future research directions that will need to be addressed in order to develop both clinically meaningful prognostic biomarkers and an evidence base that can inform public policy practice.

Objectives: This paper aims to explore whether the Persian-speaking patients of different stages, ranging from mild to moderate, have a deficit in semantic processing by comparing the performance of Alzheimer’s patients with that of the healthy individuals. Methods: The subjects of both the groups of Alzheimer’s patients and healthy control were matched for age, the state of monolingual or bilingual, and socio-cultural status. In order to assess the semantic processing ability of the subjects, Pekkala’s 2004 model was adopted. According to the model, the subjects were required to produce (say) the name of as many as category members of animals as possible within the time limit of 60 seconds. Results: The findings showed that while healthy subjects had an intact semantic processing ability, the AD patients showed weak performance in the five measures of semantic fluency including the number of true linguistic units, the total quantity of words, word size in clusters, the mean cluster size, and the cluster switching. Discussion: Conclusion: Following the framework of Troyer (1998b), it has been concluded that AD patients suffer from the semantic processing.

BACKGROUND The clinical efficacy and safety of combination therapy with acetylcholinesterase inhibitor (AChEI) and memantine compared to AChEI or memantine alone in patients with Alzheimer’s disease is inconclusive. AIMS OF THE STUDY. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the clinical efficacy and safety of combination therapy of AChEI and memantine to monotherapy with either substance in patients with moderate to severe Alzheimer's disease (Mini-Mental State Examination score is

It is widely accepted that the endocrine hormone leptin controls food intake and energy homeostasis via activation of leptin receptors expressed on hypothalamic arcuate neurons. The hippocampal formation also displays raised levels of leptin receptor expression and accumulating evidence indicates that leptin has a significant impact on hippocampal synaptic function. Thus, cellular and behavioural studies support a cognitive enhancing role for leptin as excitatory synaptic transmission, synaptic plasticity and glutamate receptor trafficking at hippocampal Schaffer collateral (SC)-CA1 synapses are regulated by leptin, and treatment with leptin enhances performance in hippocampus-dependent memory tasks. Recent studies indicate that hippocampal temporoammonic (TA)-CA1 synapses are also a key target for leptin. The ability of leptin to regulate TA-CA1 synapses has important functional consequences as TA-CA1 synapses are implicated in spatial and episodic memory processes. Moreover, degeneration is initiated in the TA pathway at very early stages of Alzheimer’s disease, and recent clinical evidence has revealed links between plasma leptin levels and the incidence of Alzheimer’s disease (AD). Additionally, accumulating evidence indicates that leptin has neuroprotective actions in various AD models, whereas dysfunctions in the leptin system accelerate AD pathogenesis. Here, we review the data implicating the leptin system as a potential novel target for AD, and the evidence that boosting the hippocampal actions of leptin may be beneficial.

BACKGROUND AND OBJECTIVE: Serum level of digitalis-like factors or sodium pump inhibitors increase under numerous pathogenic circumstances. Diminution of sodium pump activity was reported to be secondary to beta-amyloid oligomers, though the mechanism involved remains inconclusive. Therefore, this study was conducted to evaluate the alteration in serum levels of endogenous ouabain and cerebrospinal fluid (CSF) sodium in an animal model of Alzheimer’s disease, induced by intracerebroventricular injection of streptozotocin (ICV-STZ). METHODS: In this empirical study, 48 male rats were randomly divided into six groups of saline and STZ. Alzheimer’s model was induced by ICV injection of STZ (3 mg/kg) on the first and third days. CSF samples were drawn from cisterna magna, and blood samples were collected from caudal vein. Thereafter, serum levels of ouabain and CSF sodium were evaluated 2, 7, and 14 days after STZ/saline injection in the test groups. Cresyl violet and Congo red stains were applied to study neuronal morphology and presence of amyloid plaques. FINDINGS: The mean serum levels of ouabain in the STZ groups were 0.2±0.05 ng/mL vs. 0.54±0.04 ng/mL on the second day, 0.3±0.02 ng/mL vs. 0.59±0.06 ng/mL on the seventh day, and 0.2±0.07 ng/mL vs. 0.65±0.08 ng/mL on the fourteenth day. These results indicated a significant increase of endogenous ouabain in the experimental groups compared to the saline groups (p