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Tauopathies, including Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy, are characterised by the aggregation of tau into insoluble neurofibrillary tangles in the brain. Tau is subject to a range of post-translational modifications, including proteolysis, that can promote its aggregation. Neuroinflammation is a hallmark of tauopathies and evidence is growing for a role of CD8+ T cells in disease pathogenesis. CD8+ T cells release granzyme proteases but what role these proteases play in neuronal dysfunction is currently lacking. Here, we identified that granzyme A (GzmA) is present in brain tissue and proteolytically cleaves tau. Mass spectrometric analysis of tau fragments produced on digestion of tau with GzmA identified three cleavage sites at R194-S195, R209-S210 and K240-S241. Mutation of the critical Arg or Lys residues at the cleavage sites in tau or chemical inhibition of GzmA blocked the proteolysis of tau by GzmA. Development of a semi-targeted mass spectrometry approach identified peptides in tauopathy brain tissue corresponding to proteolysis by GzmA at R209-S210 and K240-S241 in tau. When expressed in cells the GzmA-cleaved C-terminal fragments of tau were highly phosphorylated and aggregated upon incubation of the cells with tauopathy brain seed. The C-terminal fragment tau195-441 was able to transfer between cells and promote aggregation of tau in acceptor cells, indicating the propensity for such tau fragments to propagate between cells. Collectively, these results raise the possibility that GzmA, released from infiltrating cytotoxic CD8+ T cells, proteolytically cleaves tau into fragments that may contribute to its pathological properties in tauopathies.

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Neurodegenerative diseases such as Alzheimer´s (AD) and physiological ageing are characterized by a decline in neurogenesis and in the polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) expression within the hippocampus and specifically in the dentate gyrus (DG). In the 3xTG-AD mouse model, which mimics the human disease in both pathological and behavioral features, this decline in PSA-NCAM is associated with the presence of Aß plaques at 9 months and Tau tangles at 12-15 months. In this work we studied the presence of PSA-NCAM at early ages (1-6 months) in the same model. Our results demonstrated that even as early as the first month of age there is a strong decrease in PSA-NCAM dendritic tree mainly altering the molecular layer (MolL) coverage affecting the synaptic plasticity and furthermore confirmed by the reduction of PSA-NCAM area density (Sv) in the 3xTG-AD. Similar and more marked early changes were seen during aging in both NTG and 3xTg-AD animals. Our results demonstrate for the first time a precipitate decrease of PSA-NCAM cells at such very early phases of the disease. This result suggests an early effect of the disease in the progression of immature and pluripotent cells resulting in an ulterior and early diminution of neurogenesis and therefore an impaired hippocampal cellular and synaptic plasticity.

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There is growing public awareness and concern regarding dementia risk. In addition, genetic testing is increasingly accessible and is at the point of being integrated into routine clinical practice. As a result, there is a pressing need for treating clinicians to have the appropriate knowledge base to request and consent for diagnostic genetic testing in cognitive clinics. We outline our approach to genetic testing in patients with Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies and vascular cognitive impairment. We discuss when to consider testing, the consenting process, and the interpretation and communication of genetic test results.

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The production of neurotoxic amyloid-ß peptides (Aß) is central to the initiation and progression of Alzheimer's disease (AD) and involves sequential cleavage of the amyloid precursor protein (APP) by ß- and γ-secretases. APP and the secretases are transmembrane proteins and their co-localisation in the same membrane-bound sub-compartment is necessary for APP cleavage. The intracellular trafficking of APP and the ß-secretase, BACE1, is critical in regulating APP processing and Aß production and has been studied in several cellular systems. Here, we summarise the intracellular distribution and transport of APP and its secretases, and the intracellular location for APP cleavage in non-polarised cells and neuronal models. In addition, we review recent advances on the potential impact of familial AD mutations on APP trafficking and processing. This is critical information in understanding the molecular mechanisms of AD progression and in supporting the development of novel strategies for clinical treatment.

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BACKGROUND: Social isolation is a well-known risk factor for poor health outcomes, including incident dementia, yet its associations with outcomes among persons living with dementia is understudied. We examined the association between social isolation and hospitalization among a nationally representative sample of older adults with and without dementia. METHODS: This observational cohort study included 5,533 community-dwelling Medicare beneficiaries from the 2015 and 2016 National Health and Aging Trends Study (NHATS). Using multivariable logistic regression analyses, we examined associations between social isolation and hospitalization in the following year, examining differences by dementia status. Social isolation was measured using a 4-item typology. Dementia was identified using a pre-specified classification in NHATS. RESULTS: 20.7% of older adults were socially isolated. Social isolation was more prevalent among persons with dementia (35.4%) than among those without dementia (19.0%) (p < .001). Among persons with dementia, social isolation was associated with 1.68 greater odds of hospitalization (CI: 1.23‒2.28), translating into a 9% average increase in the predicted probability of hospitalization for persons with dementia who were socially isolated compared to those who were not (p = 0.001). In the combined sample that included persons with and without dementia, there was a significant moderation effect of dementia on the association between social isolation and hospitalization (OR: 1.70; CI: 1.19‒2.43). CONCLUSIONS: For persons with dementia, social isolation is prevalent and associated with greater odds of subsequent hospitalization. Efforts to reduce acute healthcare utilization should explore ways to bolster social connection to improve health outcomes among persons with dementia.

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Synaptic dysfunction is an early feature in Alzheimer's disease (AD) pathogenesis and a major morphological correlate of memory deficits. Given the main synaptic location of N-methyl-D-aspartate receptors (NMDARs), their dysregulation has been implicated in these pathological effects. Here, to detect possible alterations in the expression and synaptic localisation of the GluN1 subunit in the brain of amyloidogenic APP/PS1 mice, we employed histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques. Histoblots showed that GluN1 expression was significantly reduced in the hippocampus in a layer-dependent manner, in the cortex and the caudate putamen of APP/PS1 transgenic mice at 12 months of age but was unaltered at 1 and 6 months. Using quantitative SDS-FRL, we unravelled the molecular organisation of GluN1 in seven excitatory synapse populations at a high spatial resolution in the CA1 and CA3 fields and the DG of the hippocampus in 12-month-old APP/PS1 mice. In the CA1 field, the labelling density for GluN1 in the excitatory synapses established on spines and interneurons, was significantly reduced in APP/PS1 mice compared to age-matched wild-type mice in the stratum lacunosum-moleculare but unaltered in the stratum radiatum. In the CA3 field, synaptic GluN1 was reduced in mossy fibre-CA3 pyramidal cell synapses but unaltered in the A/C-CA3 pyramidal cell synapses. In the DG, the density of GluN1 in granule cell-perforant pathway synapses was reduced in APP/PS1 mice. Altogether, our findings provide evidence of specific alterations of synaptic GluN1 in the trisynaptic circuit of the hippocampus in Aß pathology. This differential vulnerability in the disruption of NMDARs may be involved in the mechanisms causing abnormal network activity of the hippocampal circuit and cognitive impairment characteristic of APP/PS1 mice.

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BACKGROUND: General practitioners (GPs) play a crucial role in identifying cognitive impairment and dementia and providing post-diagnostic care. This study investigates (1) how promising GP consider lifestyle changes to maintain cognitive performance in general, (2) GP beliefs about the power of modifiable health and lifestyle factors to maintain cognitive performance, and (3) whether those beliefs vary by GP age. METHODS: As part of the AgeWell.de trial, GPs (n = 72) completed a process evaluation questionnaire assessing their perspectives on lifestyle changes to preserve cognitive performance in elderly patients. In greater detail, their perceived efficacy of established risk and protective factors was investigated using a 5-point Likert scale. Descriptive statistical analyses were performed for research question (1) and (2). Spearman´s rank correlations and ordinal logistic regressions were used to answer research question (3). All results were interpreted exploratively. RESULTS: GPs rated the overall chance of lifestyle changes maintaining cognitive performance quite neutral with a median score of 3.0 (IQR = 2.0). They rated the efficacy of all the modifiable health and lifestyle factors high, with increase in physical and social activity ((Mdn = 5.0, IQR = 1.0) receiving the highest ratings with the narrowest range. Spearman's rank correlation indicated a significant positive relationship between age and the belief in "Optimization of nutrition" for preventing cognitive decline and dementia (ρ = .255, p = .041). However, ordinal logistic regressions showed no significant relationships between age and GP ratings of lifestyle change efficacy. CONCLUSION: These findings highlight the positive perception of GPs on the efficacy of modifiable health and lifestyle factors for preventing cognitive decline and dementia. TRIAL REGISTRATION: The AgeWell.de trial is registered in the German Clinical Trials Register (DRKS; trial identifier: DRKS00013555, Registration Date 07 December 2017).

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Dementia is a leading cause of disability, and as the population ages, there will be a greater need for friends and family to care for people with Dementia. Unfortunately, informal care for a person with dementia is associated with poor psychological and physical health and lower quality of life of the caregiver. The aim of the present study was to understand how to best support caregivers within their communities by examining their experience of loneliness, isolation, and their relationship with well-being. The study used a representative sample of the New Zealand population in terms of ethnicity, age, gender, education, and income and asked people if they were a primary caregiver of a person with Alzheimer's Disease or related disorder. Both loneliness and isolation were linked to overall well-being; however, loneliness was a stronger predictor of satisfaction with relationships and feeling part of one's community. The findings highlight the importance of examining the multi-factorial constructs of social connectedness and question research attributing loneliness solely to reduced social involvement. As such, interventions for caregivers of a person with dementia need to target feelings of loneliness as well as their social isolation.

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Alzheimer's disease (AD) constitutes a major public-health issue of our time. Regrettably, despite our considerable understanding of the pathophysiological aspects of this disease, current interventions lead to poor outcomes. Furthermore, experimentally promising compounds have continuously failed when translated to clinical trials. Along with increased population ageing, Type 2 Diabetes Mellitus (T2DM) has become an extremely common condition, mainly due to unbalanced dietary habits. Substantial epidemiological evidence correlates T2DM with cognitive impairment as well. Considering that brain insulin resistance, mitochondrial dysfunction, oxidative stress, and amyloidogenesis are common phenomena, further approaching the common features among these pathological conditions. Metformin constitutes the first-choice drug to preclude insulin resistance in T2DM clinical management. Experimental evidence suggests that its functions might include neuroprotective effects, in addition to its hypoglycemic activity. This review aims to summarize and discuss current knowledge of experimental data on metformin on this path towards translational medicine. Finally, we discuss the controversial data of responses to metformin in vitro, and in vivo, animal models and human studies.

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Background and objective Dementia is a prevalent clinical syndrome characterized by memory impairment and cognitive dysfunction. Its global burden is expected to rise significantly, particularly in low- and middle-income countries. Understanding the spectrum of dementia types and associated risk factors is crucial for effective management. This study aims to elucidate the demographic profiles, clinical types, and risk factors of newly diagnosed dementia cases at a tertiary care hospital in India. Methods and materials A cross-sectional, hospital-based observational study was conducted on 81 patients at the Department of Medicine, Dr. D. Y. Patil Medical College, Hospital, and Research Centre, Pimpri, Pune, from February 2022 to January 2024. Ethical approval was obtained, and written consent was obtained from participants. Clinical diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria, supported by cognitive assessment tools and laboratory/radiological investigations. Inclusion criteria encompassed individuals aged 18 years or older, presenting with clinical symptoms suggestive of dementia, having a Mini-Mental State Examination (MMSE) score of less than 24 and Montreal Cognitive Assessment (MoCA) score of less than 25, according to DSM-V criteria for dementia. Exclusion criteria included individuals with a history of head trauma or those below 18 years of age. Results Of the 81 participants, the majority (74.1%) were over 60 years old, with females comprising 59.3% of the sample. Alzheimer's disease was the most prevalent dementia subtype (34.5%), followed by vascular dementia (19.7%) and mixed dementia (13.5%). Other causes included Lewy body dementia (2.46%), Parkinson's dementia (4.9%), frontotemporal dementia (4.9%), and Creutzfeldt-Jakob disease (1.2%). Reversible causes accounted for a significant proportion of cases: alcohol-associated dementia (6.1%), hypothyroid-associated dementia (3.7%), HIV-associated dementia (2.46%), herpes simplex dementia (1.2%), neurosyphilis-associated dementia (1.2%), and normal pressure hydrocephalus (NPH)-associated dementia (2.4%). Analysis of risk factors revealed distinct patterns among different dementia types, emphasizing the role of cardiovascular and metabolic health. Conclusion This study provides insights into the demographic profiles, clinical types, and dementia risk factors in India. Addressing causes and managing cardiovascular/metabolic health is crucial for dementia prevention and management. Comprehensive care strategies and ongoing research efforts are essential for improving dementia outcomes and enhancing the quality of life for affected individuals and their families.

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Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by abnormal protein deposition. With an alarming 30 million people affected worldwide, AD poses a significant public health concern. While inhibiting key enzymes such as ß-site amyloid precursor protein-cleaving enzyme 1 and γ-secretase or enhancing amyloid-ß clearance, has been considered the reasonable strategy for AD treatment, their efficacy has been compromised by ineffectiveness. Furthermore, our understanding of AD pathogenesis remains incomplete. Normal aging is associated with a decline in glucose uptake in the brain, a process exacerbated in patients with AD, leading to significant impairment of a critical post-translational modification: glycosylation. Glycosylation, a finely regulated mechanism of intracellular secondary protein processing, plays a pivotal role in regulating essential functions such as synaptogenesis, neurogenesis, axon guidance, as well as learning and memory within the central nervous system. Advanced glycomic analysis has unveiled that abnormal glycosylation of key AD-related proteins closely correlates with the onset and progression of the disease. In this context, we aimed to delve into the intricate role and underlying mechanisms of glycosylation in the etiopathology and pathogenesis of AD. By highlighting the potential of targeting glycosylation as a promising and alternative therapeutic avenue for managing AD, we strive to contribute to the advancement of treatment strategies for this debilitating condition.

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About 80 % of brain disorders have a genetic basis. The pathogenesis of most neurodegenerative diseases is associated with a myriad of genetic defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. The emergence of new sequencing technologies and tools to study the epigenome has led to identifying predictive biomarkers for earlier diagnosis, opening up the possibility of prophylactical interventions. As a result, advances in pharmacogenetics and pharmacoepigenomics now allow for personalized treatments based on the profile of each patient and the specific genetic and epigenetic mechanisms involved. This Review highlights the complexity of neurodegenerative diseases and the variability in patient responses to pharmacotherapy, emphasizing the influence of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of drugs used to treat those conditions. We specifically discuss the potential modulatory effect of several genetic polymorphisms associated with an increased risk of developing different neurodegenerative diseases. We explore genetic and genomic technologies and the potential of analyzing individual-specific drug metabolism to predict and influence drug response and associated clinical outcomes. We also provide insights into the mechanism of action of the drugs under investigation and their potential impact on disease-modifying pathways. Finally, the Review underscores the great potential of this field to enhance the effectiveness and safety of drug treatments through personalized medicine.

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Alzheimer's disease (AD) is a fatal neurological illness that worsens with time. Preventing the aggregate formation of amyloid beta protein is a promising approach to treat Alzheimer's disease. This article describes an amiable procedure for the synthesis of Olesoxime-Resveratrol (OLX-RSV) encapsulated in exosomes. By suppressing Aß1-42 aggregation and crossing the blood-brain barrier also known as BBB after intravenous treatment without resulting in any discernible damage, the nanocomposite demonstrated good biocompatibility. A variety of characterization technique including particle size, TEM, and in vitro drug release experiments, were used to characterize the exosomes. Human Neuroblastoma (SHSY5Y) cells were used to test the cytotoxicity and viability of cells of the formulation using the Cell Counting Kit-8 assay. The prepared OLX-RSV-loaded exosomes were tested for their ability to suppress Aß1-42 in SHSY5Y Cells by analyzing the amyloid samples using CD spectra. The effects of apoptosis on Human neuroblastoma cells were studied using cytofluorometry. The parameters of SOD, caspase-3 and the ability to scavenge reactive oxygen species (ROS) were also evaluated. The behavioral outcomes of Morris water maze test demonstrated that OLX-RSV-loaded exosomes significantly enhanced the APP/PS1 mice's capacity to learn and remember spatial cues. Therefore, we hypothesized that OLX-RSV-loaded exosomes could be a useful and efficient method in the treatment of AD.

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Alterations in cognitive and non-cognitive cerebral functions characterize Alzheimer's disease (AD). Cortical and hippocampal impairments related to extracellular accumulation of Aß in AD animal models have been extensively investigated. However, recent reports have also implicated intracellular Aß in limbic regions, such as the nucleus accumbens (nAc). Accumbal neurons express high levels of inhibitory glycine receptors (GlyRs) that are allosterically modulated by ethanol and have a role in controlling its intake. In the present study, we investigated how GlyRs in the 2xTg mice (AD model) affect nAc functions and ethanol intake behavior. Using transgenic and control aged-matched litter mates, we found that the GlyRα2 subunit was significantly decreased in AD mice (6-month-old). We also examined intracellular calcium dynamics using the fluorescent calcium protein reporter GCaMP in slice photometry. We also found that the calcium signal mediated by GlyRs, but not GABAAR, was also reduced in AD neurons. Additionally, ethanol potentiation was significantly decreased in accumbal neurons in the AD mice. Finally, we performed drinking in the dark (DID) experiments and found that 2xTg mice consumed less ethanol on the last day of DID, in agreement with a lower blood ethanol concentration. 2xTg mice also showed lower sucrose consumption, indicating that overall food reward was altered. In conclusion, the data support the role of GlyRs in nAc neuron excitability and a decreased glycinergic activity in the 2xTg mice that might lead to impairment in reward processing at an early stage of the disease.

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Background: There is a common agreement that Alzheimers disease (AD) is inherently complex; otherwise, a general disagreement remains on its etiological underpinning, with numerous alternative hypotheses having been proposed. Objective: To perform a scoping review of original manuscripts describing hypotheses and theories of AD published in the past decades. Results: We reviewed 131 original manuscripts that fulfilled our inclusion criteria out of more than 13,807 references extracted from open databases. Each entry was characterized as having a single or multifactorial focus and assigned to one of 15 theoretical groupings. Impact was tracked using open citation tools. Results: Three stages can be discerned in terms of hypotheses generation, with three quarter of studies proposing a hypothesis characterized as being single-focus. The most important theoretical groupings were the Amyloid group, followed by Metabolism and Mitochondrial dysfunction, then Infections and Cerebrovascular. Lately, evidence towards Genetics and especially Gut/Brain interactions came to the fore. Conclusions: When viewed together, these multi-faceted reports reinforce the notion that AD affects multiple sub-cellular, cellular, anatomical, and physiological systems at the same time but at varying degree between individuals. The challenge of providing a comprehensive view of all systems and their interactions remains, alongside ways to manage this inherent complexity.

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Several in vivo studies have shown that systemic inflammation, mimicked by LPS, triggers an inflammatory response in the CNS, driven by microglia, characterized by an increase in inflammatory cytokines and associated sickness behavior. However, most studies induce relatively high systemic inflammation, not directly compared with the more common low-grade inflammatory events experienced in humans during the life course. Using mice, we investigated the effects of low-grade systemic inflammation during an otherwise healthy early life, and how this may precondition the onset and severity of Alzheimer's disease (AD)-like pathology. Our results indicate that low-grade systemic inflammation induces sub-threshold brain inflammation and promotes microglial proliferation driven by the CSF1R pathway, contrary to the effects caused by high systemic inflammation. In addition, repeated systemic challenges with low-grade LPS induce disease-associated microglia. Finally, using an inducible model of AD-like pathology (Line 102 mice), we observed that preconditioning with repeated doses of low-grade systemic inflammation, prior to APP induction, promotes a detrimental effect later in life, leading to an increase in Aß accumulation and disease-associated microglia. These results support the notion that episodic low-grade systemic inflammation has the potential to influence the onset and severity of age-related neurological disorders, such as AD.

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BACKGROUND: Although the family plays a pivotal role in older adults' care, there is limited research on how evolving demographic trends affect older adults' support networks and how the trends vary by race. To fill this gap, we examine the influence of shifting family demographics on future care needs for older adults with dementia, emphasizing the unequal health and potential caregiving burdens by race in the U.S. METHODS: Using demographic models of kinship, we estimate the availability of potential caregivers, and dementia prevalence among one's kin by race, kin type, and the age of a focal person from 2000 to 2060. We introduce an index called the Dementia Dependency Ratio to assess dementia caregiving demands at the population level, taking into account the age and kinship structure of the population. RESULTS: Our findings suggest that Black individuals tend to have more children, grandchildren, and nieces/nephews as they age. However, Black individuals also tend to have more kin with dementia compared to their White counterparts. This elevated prevalence of dementia among Black kinship networks counterbalances the advantage of having more kin as potential caregivers. A further projection analysis suggests that the racial gap in caregiving demand within the kinship network will widen in the next four decades if the racial gap in dementia prevalence remains unchanged. CONCLUSIONS: These findings emphasize the urgency of reducing racial inequality in dementia prevalence rates and increasing public support for families with extended members affected by dementia. With the shrinkage of nuclear families and population aging in the next few decades, extended family members may undertake more caregiving responsibilities for dementia. We call for a kinship perspective in understanding dementia care in future research.

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Introduction: Remote monitoring technologies (RMTs) can measure cognitive and functional decline objectively at-home, and offer opportunities to measure passively and continuously, possibly improving sensitivity and reducing participant burden in clinical trials. However, there is skepticism that age and cognitive or functional impairment may render participants unable or unwilling to comply with complex RMT protocols. We therefore assessed the feasibility and usability of a complex RMT protocol in all syndromic stages of Alzheimer's disease and in healthy control participants. Methods: For 8 weeks, participants (N = 229) used two activity trackers, two interactive apps with either daily or weekly cognitive tasks, and optionally a wearable camera. A subset of participants participated in a 4-week sub-study (N = 45) using fixed at-home sensors, a wearable EEG sleep headband and a driving performance device. Feasibility was assessed by evaluating compliance and drop-out rates. Usability was assessed by problem rates (e.g., understanding instructions, discomfort, forgetting to use the RMT or technical problems) as discussed during bi-weekly semi-structured interviews. Results: Most problems were found for the active apps and EEG sleep headband. Problem rates increased and compliance rates decreased with disease severity, but the study remained feasible. Conclusions: This study shows that a highly complex RMT protocol is feasible, even in a mild-to-moderate AD population, encouraging other researchers to use RMTs in their study designs. We recommend evaluating the design of individual devices carefully before finalizing study protocols, considering RMTs which allow for real-time compliance monitoring, and engaging the partners of study participants in the research.

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment, a loss of cholinergic neurons, and cognitive decline that insidiously progresses to dementia. The pathoetiology of AD is complex, as genetic predisposition, age, inflammation, oxidative stress, and dysregulated proteostasis all contribute to its development and progression. The histological hallmarks of AD are the formation and accumulation of amyloid-ß plaques and interfibrillar tau tangles within the central nervous system. These histological hallmarks trigger neuroinflammation and disrupt the physiological structure and functioning of neurons, leading to cognitive dysfunction. Most treatments currently available for AD focus only on symptomatic relief. Disease-modifying treatments (DMTs) that target the biology of the disease in hopes of slowing or reversing disease progression are desperately needed. This narrative review investigates novel DMTs and their therapeutic targets that are either in phase three of development or have been recently approved by the U.S. Food and Drug Administration (FDA). The target areas of some of these novel DMTs consist of combatting amyloid or tau accumulation, oxidative stress, neuroinflammation, and dysregulated proteostasis, metabolism, or circadian rhythm. Neuroprotection and neuroplasticity promotion were also key target areas. DMT therapeutic target diversity may permit improved therapeutic responses in certain subpopulations of AD, particularly if the therapeutic target of the DMT being administered aligns with the subpopulation's most prominent pathological findings. Clinicians should be cognizant of how these novel drugs differ in therapeutic targets, as this knowledge may potentially enhance the level of care they can provide to AD patients in the future.

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OBJECTIVES: In this study, we examine the measurement of cognition in different racial/ethnic groups to move towards a less biased and more inclusive set of measures for capturing cognitive change and decline in older adulthood. METHODS: We use data from Round 2 (N=3377) and Round 3 (N=4777) of the National Social Life, Health, and Aging Project (NSHAP) and examine the study's Survey Adjusted version of the Montreal Cognitive Assessment (MoCA-SA). We employ exploratory factor analyses to explore configural invariance by racial/ethnic group. Using modification indexes, two-parameter item response theory models, and split-sample testing, we identify items that seem robust to bias by race. We test the predictive validity of the full (18-item) and short (4-item) MoCA-SAs using self-reported dementia diagnosis, instrumental activities of daily living (IADLs), proxy reports of dementia, proxy reports of dementia-related death, and National Death Index reports of dementia-related death. RESULTS: We found that four measures out of the 18 used in NSHAP's MoCA-SA formed a scale that was more robust to racial bias. The shortened form predicted consequential outcomes as well as NSHAP's full MoCA-SA. The short form was also moderately correlated with the full form. DISCUSSION: Although sophisticated structural equation modeling techniques would be preferrable for assuaging measurement invariance by race in NSHAP, the shortened form of the MoCA-SA provides a quick way for researchers to carry out robustness checks and to see if the disparities and associations by race they document are "real" or the product of artifactual bias.