The Alzheimer’s Dementia Patients’ Observed Illness Course and Experience in Ghana and Care Lessons to Be Learnt: A Mental Health Professional’s Perspective

Alzheimer’s disease (AD) and associated dementia patient numbers continue to increase globally with associated economic costs to healthcare systems. Of note is the increase in numbers in lower and middle-income countries (LMICs) including Sub-Saharan African (SSA) countries, which already face challenges with their health budgets from communicable and non-communicable diseases. Ghana, an SSA country, faces the problem of healthcare budgetary difficulties and the additional impact of AD as a consequence of increasing population strata of old aged persons (OAPs) due to the demographic transition effect. This article uses examples of known patients’ illness courses to give a perspective on the lived experience of patients with dementia (PWD) in Ghana, living amongst a populace with a culture of stigmatization of PWD, and a relatively fragile public mental health system (PMHS) for those with mental illness, including AD. The lived experience of AD patients is characterised by stigmatisation, discrimination, non-inclusiveness, diminished dignity and human rights abuses in the face of their mental disability, and eventually death. This article is an advocacy article giving voice to the voiceless and all persons suffering from AD and other dementias in Ghana, whilst pleading for a call to action from healthcare professionals and responsible state agencies.

Clinical Study on the Treatment of Senile Alzheimer’s Dementia with Sodium Oligomannate Combined with Memantine Hydrochloride

Objective:To analyze the clinical effects of sodium oligomannate combined with memantine hydrochloride in the treatment of senile Alzheimer’s dementia.Methods:Sixty-eight cases of Alzheimer’s dementia treated at the Second People’s Hospital of Fujian University of Traditional Chinese Medicine from March 2020 to March 2022 were selected as the study subjects.The patients were divided into two groups based on different treatment methods:the control group(treated with memantine hydrochloride,34 cases)and the treatment group(treated with sodium oligomannate+memantine hydrochloride,34 cases).Cognitive function,activities of daily living,neurotransmitters,serum intestinal flora metabolic markers,inflammatory factors,neurotrophic factors,and adverse reactions were compared between the two groups.Results:The treatment group showed better cognitive function,quality of life scores,and levels of relevant metabolic markers in the body compared to the control group,with statistically significant differences(P<0.05).The incidence of adverse reactions between the two groups(treatment group:2%;control group:4%)was not statistically significant(χ^(2)=0.731,P=0.393).Conclusion:Sodium oligomannate combined with memantine hydrochloride has better efficacy than the control group for treating senile Alzheimer’s dementia.It significantly improves and restores cognitive function and daily living abilities,benefits neurotransmitter secretion and internal regulation,upregulates the expression of neurotrophic factors,and has fewer adverse reactions,making it a treatment worthy of further clinical promotion and application.

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Emerging Novel Therapeutic Approaches for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly consists of symptomatic therapy and disease-modifying therapy (DMT). Several monotherapies including small molecules or antibodies have been evaluated through multiple clinical trials, but a very few have been approved by the USFDA to intervene the disease’s pathogenesis. Past research has shown multifactorial nature of AD, therefore, multi-target drugs were proposed to target different pathways at the same time, however, currently no rationally designed multi-target directed ligand (MTDL) has been clinically approved. Different combinations and bispecific antibodies are also under development. Novel approaches like stem cell-based therapies, microRNAs, peptides, ADCs and vaccines cast a new hope for AD treatment, however, a number of questions remained to be answered prior to their safe and effective clinical translation. This review explores the small molecules, MTDL, and antibodies (monospecific and bispecific) for the treatment of AD. Finally, future perspectives (stem cell therapy, PROTAC approaches, microRNAs, ADC, peptides and vaccines) are also discussed with regard to their clinical applications and feasibility.

Converging links between adult-onset neurodegenerative Alzheimer’s disease and early life neurodegenerative neuronal ceroid lipofuscinosis?

Evidence from genetics and from analyzing cellular and animal models have converged to suggest links between neurodegenerative disorders of early and late life.Here,we summarize emerging links between the most common late life neurodegenerative disease,Alzheimer’s disease,and the most common early life neurodegenerative diseases,neuronal ceroid lipofuscinoses.Genetic studies reported an overlap of clinically diagnosed Alzheimer’s disease and mutations in genes known to cause neuronal ceroid lipofuscinoses.Accumulating data strongly suggest dysfunction of intracellular trafficking mechanisms and the autophagy-endolysosome system in both types of neurodegenerative disorders.This suggests shared cytopathological processes underlying these different types of neurodegenerative diseases.A better understanding of the common mechanisms underlying the different diseases is important as this might lead to the identification of novel targets for therapeutic concepts,the transfer of therapeutic strategies from one disease to the other and therapeutic approaches tailored to patients with specific mutations.Here,we review dysfunctions of the endolysosomal autophagy pathway in Alzheimer’s disease and neuronal ceroid lipofuscinoses and summarize emerging etiologic and genetic overlaps.

Treatment Efficacy of Photobiomodulation for Moderate and Advanced Dementia or Alzheimer’s Disease: Case Studies

Extensive research is ongoing in the use of Photobiomodulation (PBM, often referred to as low-level or cold laser therapy) to treat Alzheimer’s disease as well as other debilitating diseases. The following case studies further confirm that PBM could be a breakthrough approach to limit the progression of insidious diseases. We present four cases, two with mild to moderate dementia and two with more advanced symptoms. Several publications have shown beneficial results, however, several weeks of daily treatments were necessary. The cases described here suggest that moderate and advanced dementia cases can be significantly improved with three or four eight-minute treatments over a 5 - 7-day period when using super-pulsing technology on Monday-Wednesday-Friday schedule (Figure 1). Gives a brief visual explanation of super-pulsing versus continuous wave technology.

Correlation between Alzheimer’s Disease and Dementia with Lewy Bodies Scores Using VSRAD Advance

The objective of the study was to explore the relationship between the indicators of Alzheimer’s disease and dementia with Lewy bodies using the voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) advance. Among 36 patients with suspected dementia, patients with Alzheimer’s disease and dementia with Lewy bodies were identified using VSRAD advance from March 1 to October 30, 2019. All patients underwent brain Magnetic Resonance Imaging (MRI). We diagnosed Alzheimer’s disease using Volume of Interest (VOI) in the Medial Temporal Lobe (MTL) atrophy ratio > 2 and dementia with Lewy bodies using both VOI in the MTL atrophy ratio ≤ 2 and gray/white matter atrophy ratio ≥ 0.2. The correlation between the indicators of Alzheimer’s disease and dementia with Lewy bodies was calculated. The number of patients classified as having Alzheimer’s disease and dementia with Lewy bodies was 25 and 11, respectively. In the Alzheimer’s disease group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem gray matter was r = -0.40 (p = 0.045). In dementia with Lewy bodies group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem white matter was r = -0.78 (p < 0.01). Using VSRAD advance, gray matter atrophy and dorsal brainstem grey/white matter atrophy were found to be negatively correlated in Alzheimer’s disease and dementia with Lewy bodies.

阿尔茨海默病(Alzheimer’s Disease,AD)与动力相关蛋白1(dynamin-related protein 1,Drp1)

阿尔茨海默病(AD)已成为威胁老年人生活的一种常见病,对老年人的生活质量有着严重的影响,目前尚无有效地防治方法。最新研究发现在阿尔茨海默病的病理发生中,神经细胞伴有显著的线粒体代谢紊乱和动态变化的异常,其中动力相关蛋白1(Drp1)是参与线粒体动态变化的关键分子。深入研究阿尔茨海默病中线粒体动态变化的异常及Drp1等关键分子的作用机制,对于揭示AD的发生机制及寻找药物作用靶点具有重要意义。综述了Drp1在阿尔茨海默病中的调控机制。

Dementia and Cognitive Impairment Reduction after Laser Transcatheter Treatment of Alzheimer’s Disease

Reduced cerebral perfusion and microcirculation are found among AD causes, which should be considered in the development of new treatments for the disease. 165 patients with AD were examined. The examination plan included clinical assessment of dementia severity (CDR), cognitive function assessment (MMSE), laboratory examination, cerebral scintigraphy (SG), rheoencephalography (REG), cerebral CT and MRI, morphometric AD stages assessment (TDR) and cerebral multi-gated angiography (MUGA). 89 patients aged 34 - 79 (average age 67) were selected for the treatment: 31 (34.83%) male, 58 (65.17%) female patients. According to their AD stage, the patients were divided into: TDR-0 (preclinical stage)—10 (11.24%) patients, TDR-1 (early stage with mild dementia, mild cognitive impairment)—28 (31.46%) patients, TDR-2 (medium stage with moderate dementia, cognitive impairment sufficiently persistent)—34 (38.20%) patients, TDR-3 (late stage with sufficiently severe dementia and cognitive impairment)—17 (19.10%) patients. Test Group—46 (51.68%) patients—had transcatheter treatment with low-energy lasers. Control Group—43 (48.31%)—had conservative treatment with Memantin and Rivastigmine. The Test Group had cerebral microcirculation improvement leading to permanent dementia reduction and cognitive recovery which allowed transferring the patients to a lighter TDR group or withdrawing them from the scale. Control Group patients with earlier AD stages (TDR-0, TDR-1, TDR-2) obtained stabilization for a period of 6 months-3 years, with subsequent growth of dementia and cognitive impairment;patients with late AD stage (TDR-3) showed further increase of cognitive impairment and dementia. Transcatheter treatment allows reducing the effects of dyscirculatory angiopathy of Alzheimer’s type (DAAT) improving cerebral microcirculation and metabolism, which leads to permanent dementia regression and cognitive impairment reduction. These data show that AD treatment should be comprehensive and aimed at both the recovery of cerebral microcirculation and blood supply and the normalization of amyloid beta metabolism in the cerebral tissue.

Novel Computer-Aided Diagnosis System for the Early Detection of Alzheimer’s Disease

Aging is a natural process that leads to debility,disease,and dependency.Alzheimer’s disease(AD)causes degeneration of the brain cells leading to cognitive decline and memory loss,as well as dependence on others to fulfill basic daily needs.AD is the major cause of dementia.Computer-aided diagnosis(CADx)tools aid medical practitioners in accurately identifying diseases such as AD in patients.This study aimed to develop a CADx tool for the early detection of AD using the Intelligent Water Drop(IWD)algorithm and the Random Forest(RF)classifier.The IWD algorithm an efficient feature selection method,was used to identify the most deterministic features of AD in the dataset.RF is an ensemble method that leverages multiple weak learners to classify a patient’s disease as either demented(DN)or cognitively normal(CN).The proposed tool also classifies patients as mild cognitive impairment(MCI)or CN.The dataset on which the performance of the proposed CADx was evaluated was sourced from the Alzheimer’s Disease Neuroimaging Initiative(ADNI).The RF ensemble method achieves 100%accuracy in identifying DN patients from CN patients.The classification accuracy for classifying patients as MCI or CN is 92%.This study emphasizes the significance of pre-processing prior to classification to improve the classification results of the proposed CADx tool.

Prevalence of cerebrospinal fluid Alzheimer disease-like pattern in atypical dementias

BACKGROUND: Differential diagnosis between Frontotemporal Dementia (FTD), Corticobasal Syndrome (CBS), Progressive Supranuclear Palsy Syndrome (PSP), FTD with motor neuron disease (FTD-MND) is often challenging, because of the occurrence of atypical cases. Autopsy series have identified Alzheimer Disease (AD) pathology in a consistent percentage of patients with atypical dementias. It has been demonstrated that Cerebrospinal Fluid (CSF) Tau/Aβ42 dosage is a reliable marker for AD. OBJECTIVE: To evaluate the presence and percentage of CSF AD-like patterns (high CSF tau/Aβ42 ratio) in patients with atypical dementias in order to identify an ongoing AD neurodegenerative process. METHODS: One hundred seventy two consecutive patients fulfilling current clinical criteria for behavioural variant FTD (bvFTD, n = 73), agrammatic variant of Primary Progressive Aphasia (avPPA, n = 19), semantic variant of PPA (svPPA, n = 12), FTD-MND (n = 5), CBS (n = 42), PSP (n = 21) were recruited and underwent CSF analysis. CSF AD-like and non AD (nAD-like) patterns were identified. RESULTS: CSF AD-like pattern was reported in 6 out of 73 cases (8.2%) in the bvFTD group, in 3 out of 19 (15.8%) in the avPPA group, and in 7 out of 42 (16.7%) in the CBS group. One out of 12 (8.3%) of svPPA had CSF AD-like pattern. None of patients FTD-MND and PSP had CSF AD-like pattern. No differences in demographic characteristics were detected between subgroups in each phenotype. CONCLUSIONS: Our findings convey that the CSF tau/ Aβ42 ratio could be found in a proportion of cases with clinical bvFTD, avPPA and CBD. Detecting anon-going AD pathological process in atypical dementias has several implications for defining distinctive therapeutic approaches, guiding genetic screening and helping in patients’ selection in future clinical trials.

Neuroprotective Effect of Phyllanthus acidus L. on Learning and Memory Impairment in Scopolamine-Induced Animal Model of Dementia and Oxidative Stress: Natural Wonder for Regulating the Development and Progression of Alzheimer’s Disease

Nature is the best source of complementary and alternative medicine. The plant Phyllanthus acidus (PA) L. has been used traditionally in pain, inflammatory and oxidative stress related disorders. In this consequence, methanolic extract of PA (MEPA) was selected to explore the ability of this plant to enhance cognitive function, brain antioxidant enzymes and anti-acetylcholinesterase activity which can be used for the treatment of oxidative stress related disorders like Alzheimer’s disease (AD). The purpose of this study was to investigate the neuroprotective effect of MEPA on learning and memory impairment in scopolamine-induced rats of dementia and oxidative stress. Treatment with MEPA (i.e., 100 and 200 mg/kg b.w.) was investigated in scopolamine-treated Swiss albino male rats for 14 days and its neuroprotective effects were examined using Elevated Plus Maze (EPM) test, Passive Avoidance (PA) test, Novel Object Recognition (NOR) test, Morris Water Maze (MWM) test as well as level of antioxidant enzymes such as catalase (CAT), super oxide dismutase (SOD), glutathione reductase (GSR), glutathione-S-transferase (GST), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), lipid peroxidation (TBARS) contents and acetylcholinesterase (AChE) activity in rat brain tissue homogenates. Administration of MEPA significantly (P < 0.05, P < 0.01;P < 0.01) decreased RTL (retention transfer latency) in rats on 7th and 14th day compared to the disease control and control group in the EPM test. In PA test the doses of MEPA suggestively (P < 0.05, P < 0.001;P < 0.05, P < 0.01) increased STL (step-through latency) in rats on 7th and 14th day with respect to disease control and control group. For NOR test administration of MEPA considerably (P < 0.01, P < 0.001;P < 0.01) increased the DI (discrimination index) in rats with respect to that of disease control and control group. The doses of MEPA markedly (P < 0.05, P < 0.01;P < 0.01) decreased EL (escape latency) and significantly (P < 0.01, P < 0.001;P < 0.05, P < 0.01) increased TSTQ (time spent in the target quadrant) on successive days as compared to that of disease control and control group in the acquisition trial of MWM test. In case of probe trial of MWM test MEPA administration considerably (P < 0.01;P < 0.05, P < 0.01) increased TSTQ and significantly (P < 0.05, P < 0.01;P < 0.05, P < 0.01) increased TSA (time spent in the annuli) in rats on successive days as compared to that of disease control and control group. MEPA administration significantly (P < 0.05, P < 0.01, P < 0.001;P < 0.05, P < 0.01) increased the level of CAT, SOD, GSR, GST GSH, GSH-Px and markedly (P < 0.01;P < 0.01, P < 0.001) decreased TBARS level through inhibiting lipid peroxidation as well as significantly (P < 0.01, P < 0.001;P < 0.05, P < 0.01, P < 0.001) decreasing AChE activity in rats brain compared to the disease control and control group. The present study demonstrates that MEPA showed the neuroprotective effect by improving cognitive functions and reduces oxidative stress by increasing the level of brain antioxidant enzymes as well as decreasing lipid peroxidation and acetylcholinesterase activity. Therefore, this plant extract can be used for enhancing learning, memory, antioxidant potentiality and anti-acetylcholinesterase activity in neurodegenerative disorders like AD.

Evaluation of retinal and choroidal changes in patients with Alzheimer’s type dementia using optical coherence tomography angiography

AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and to explore changes in retinal function.METHODS:Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled.All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area,including the vessel length density,the vessel perfusion density and the area of foveal avascular zone(FAZ),as well as the choroidal thickness.The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters.We also recorded the flash ERGs using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.RESULTS:The vessel parameters[Pvessel length density=0.005 and Pvessel perfusion density=0.006]and average choroid thickness(P<0.001)in the macular area of the ATD group was less than the control group.The FAZ area was statistically significantly enlarged in the ATD group(P<0.001).These parameters were correlated with the Mini-Mental State Examination(MMSE)score and the Montreal Cognitive Assessment(MoCA).CONCLUSION:Patients with ATD exhibit decreases in the parameters associated with fundus.In addition,these indicators significantly correlate with the MMSE score and the MoCA score.OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.

The tomography dementia rating scale (TDR)—The rating scale of Alzheimer’s disease stages

The purpose of this research is to develop a morphologically determined scale—the Tomography Dementia Rating scale (TDR) to diagnose AD stages, based on the measurement of the severity of voluminal atrophic changes of the temporal lobes of the brain detected among patients during CT and MRI at various stages of the disease. The research included 140 patients aged 28 - 79. Test Group comprised 81 patients aged 34 - 79 suffering from various AD stages. Control Group consisted of 59 patients aged 28 - 78 who had various types of brain lesions with manifestations of dementia and cognitive impairment but who did not suffer from AD. CT and MRI data obtained has made it possible to create a scale that allows determining the severity of atrophic changes in the temporal lobes at each stage of AD development: 1) Pre-clinical AD stage—TDR-0: temporal lobes atrophy with a 4% - 8% decrease in tissue mass (corresponds to 26 - 28 MMSE points);2) Early AD Stage—mild dementia—TDR-1: temporal lobes atrophy with a 9% - 18% decrease in tissue mass (corresponds to CDR-1 and to 20 - 25 MMSE points);3) Middle AD stage—moderate dementia—TDR-2: temporal lobes atrophy with a 19% - 32% decrease in tissue mass (corresponds to CDR-2 and to 12 - 19 MMSE points);4) Late AD stage—heavy dementia—TDR-3: temporal lobes atrophy with a 33% - 62% decrease in tissue mass (corresponds to CDR-3 and to 7 - 11 MMSE points). Thereby, the developed Tomography Dementia Rating scale (TDR) complements the Clinical Dementia Rating scale (CDR) and allows a correct and objective determination of AD stages as well as an easy differentiation of existing lesions with neurodegenerative changes characteristic for other diseases accompanied by dementia and cognitive impairment.

The Prevalence of Alzheimer’s Disease and Dementia in Alzheimer’s Disease in Patients of Long-Term Nursing Home Care in the Podlaskie Province in Poland

The prevalence of Alzheimer’s disease and dementia in Alzheimer’s disease according to the International Statistical Classification of Diseases and Related Health Problems ICD-10 in patients of long-term nursing home care in the Podlaskie province is not yet known. The aim of the study was the socio-demographic assessment of the long-term nursing home care patients with diagnosed Alzheimer’s disease and socio-demographic assessment of the long-term nursing home care patients with dementia in Alzheimer’s disease. Data concerning all 7637 patients who received long- term nursing home care benefits in the years from 2008 to 2013 in the Podlaskie province were investigated. Alzheimer’s disease was diagnosed in 2.972% of patients at the average age of 79.82 years (±8.05). The disease was diagnosed more frequently (78.4%) and earlier in women (from 44 years of age). Dementia in Alzheimer’s disease was diagnosed in 210 patients (2.749%). The mean age of patients with Alzheimer’s dementia was 81.72 years (±7.73). Stupor in patients under 65 years more frequently affected women. Research confirms the impact of Alzheimer’s disease and dementia in Alzheimer’s disease on daily activity performance. Studies suggest that the high rate of Alzheimer’s disease and dementia in Alzheimer’s disease is due to ethnic and national differences associated with learning at home and in schools in the Podlaskie province.

The Efficacy and Safety of Yokukansankachimpihange for Treating Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: An Open-Label Pilot Study

Previous clinical trials have demonstrated the efficacy of yokukansan, a traditional Japanese medicine, for the treatment of behavioral and psychological symptoms of dementia (BPSD). However, less evidence is available for the treatment of BPSD with yokukansankachimpihange (YKSCH), which consists of yokukansan and two additional herbal ingredients. The present study was conducted to investigate the efficacy and safety of YKSCH for treating BPSD in patients with Alzheimer’s disease (AD). We enrolled outpatients with mild-to-moderate AD who exhibited BPSD and obtained a Neuropsychiatric Inventory (NPI) score of >3 including subscale scores for “agitation”, “anxiety”, “irritability”, and “sleep and night-time behavior change”. A daily YKSCH dose of 7.5 g was administered for 12 weeks with concomitant administration of anti-dementia medication. BPSD was evaluated using the NPI at baseline and every 4 weeks during the intervention. We also examined apathy using the Japanese translation of the Apathy Scale, the short version of the Japanese version of the Zarit Caregiver Burden Interview, and the Modified Crichton Rating Scale for Predicting Activities of Daily Living. Cognitive dysfunction was evaluated using the Mini Mental State Examination and the AD Assessment Scale-Cognitive (Japanese version). Five participants were enrolled. The NPI total score tended to decrease between the baseline and 8-week evaluations during the YKSCH intervention (Wilcoxon signed rank test, P = 0.063). In terms of the NPI subscale scores, “apathy”, “agitation”, “delusions”, and “sleep and night-time behavior change” decreased after the intervention in those who exhibited each symptom at baseline. There were no significant differences in the other scores examined. No serious adverse events were observed. YKSCH could ameliorate BPSD in patients with mild-to-moderate AD with agitation, anxiety, irritability, and sleep and night-time behavior change, and it was well-tolerated.

Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease

Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.

Inter-individual differences in the responses to aerobic exercise in Alzheimer’s disease: Findings from the FIT-AD trial

Background:Despite the strong evidence of aerobic exercise as a disease-modifying treatment for Alzheimer’s disease(AD)in animal models,its effects on cognition are inconsistent in human studies.A major contributor to these findings is inter-individual differences in the responses to aerobic exercise,which was well documented in the general population but not in those with AD.The purpose of this study was to examine inter-individual differences in aerobic fitness and cognitive responses to a 6-month aerobic exercise intervention in community-dwelling older adults with mild-to-moderate dementia due to AD.Methods:This study was a secondary analysis of the Effects of Aerobic Exercise for Treating Alzheimer’s Disease(FIT-AD)trial data.Aerobic fitness was measured by the shuttle walk test(SWT),the 6-min walk test(6MWT),and the maximal oxygen consumption(VO2max)test,and cognition by the AD Assessment Scale-Cognition(ADAS-Cog).Inter-individual differences were calculated as the differences in the standard deviation of 6-month change(SDR)in the SWT,6MWT,VO2max,and ADAS-Cog between the intervention and control groups.Results:Seventy-eight participants were included in this study(77.4±6.3 years old,mean±SD;15.7±2.8 years of education;41%were female).VO2max was available for 26 participants(77.7±7.1 years old;14.8±2.6 years of education;35%were female).The SDR was 37.0,121.1,1.7,and 2.3 for SWT,6MWT,VO2max,and ADAS-Cog,respectively.Conclusion:There are true inter-individual differences in aerobic fitness and cognitive responses to aerobic exercise in older adults with mild-tomoderate dementia due to AD.These inter-individual differences likely underline the inconsistent cognitive benefits in human studies.

Depressive Symptom Endorsement among Alzheimer’s Disease, Vascular Dementia and Mild Cognitive Impairment

Background: The Geriatric Depression Scale (GDS) is widely used to assess depressive symptoms in clinical and research settings. This study utilized a 4 factor solution for the 30-item GDS to explore differences in the presentation of depressive symptoms in various types of cognitive impairment. Method: Retrospective chart review was conducted on 254 consecutive cases of community dwelling elderly newly diagnosed with mild Alzheimer’s Dementia (AD) n = 122, mild Vascular Dementia (VaD) n = 71 or Amnestic Mild Cognitive Impairment (aMCI) n = 32 and Non-Amnestic MCI (nMCI) n = 29. Results: Analysis revealed no significant differences (p 05). No statistically significant differences were found between VaD and nMCI or between the MCI groups. Conclusions: Support is provided for the use of GDS subscales in a wide range of cognitively impaired elderly. This study suggests in mild dementia the number and type of depressive symptoms vary significantly between AD and VaD. There are indications that aMCI patients are similar in their symptom endorsement to AD and nMCI are similar to VaD which is consistent with some of the notions regarding likely trajectories of the respective MCI groups.

Early Detection of Alzheimer’s Disease Based on Laplacian Re-Decomposition and XGBoosting

The precise diagnosis of Alzheimer’s disease is critical for patient treatment,especially at the early stage,because awareness of the severity and progression risks lets patients take preventative actions before irreversible brain damage occurs.It is possible to gain a holistic view of Alzheimer’s disease staging by combining multiple data modalities,known as image fusion.In this paper,the study proposes the early detection of Alzheimer’s disease using different modalities of Alzheimer’s disease brain images.First,the preprocessing was performed on the data.Then,the data augmentation techniques are used to handle overfitting.Also,the skull is removed to lead to good classification.In the second phase,two fusion stages are used:pixel level(early fusion)and feature level(late fusion).We fused magnetic resonance imaging and positron emission tomography images using early fusion(Laplacian Re-Decomposition)and late fusion(Canonical Correlation Analysis).The proposed system used magnetic resonance imaging and positron emission tomography to take advantage of each.Magnetic resonance imaging system’s primary benefits are providing images with excellent spatial resolution and structural information for specific organs.Positron emission tomography images can provide functional information and the metabolisms of particular tissues.This characteristic helps clinicians detect diseases and tumor progression at an early stage.Third,the feature extraction of fused images is extracted using a convolutional neural network.In the case of late fusion,the features are extracted first and then fused.Finally,the proposed system performs XGB to classify Alzheimer’s disease.The system’s performance was evaluated using accuracy,specificity,and sensitivity.All medical data were retrieved in the 2D format of 256×256 pixels.The classifiers were optimized to achieve the final results:for the decision tree,the maximum depth of a tree was 2.The best number of trees for the random forest was 60;for the support vector machine,the maximum depth was 4,and the kernel gamma was 0.01.The system achieved an accuracy of 98.06%,specificity of 94.32%,and sensitivity of 97.02%in the case of early fusion.Also,if the system achieved late fusion,accuracy was 99.22%,specificity was 96.54%,and sensitivity was 99.54%.