Alzheimer\'s disease and related dementias (ADRD) are a spectrum of disorders characterized by cognitive decline, which pose significant challenges for both affected individuals and their caregivers. Previous literature has focused on patient family surveys which do not always capture the breadth of authentic experiences of the caregiver. Online social media platforms provide a space for individuals to share their experiences and obtain advice toward caring for those with ADRD. This study leverages Reddit, a platform frequented by caregivers seeking advice for caring for a family member with advice for ADRD. To identify the topics of discussion or advice that most caregivers seek and sought after, we employed structured topic modeling techniques such as BERTopic to analyze the content of these posts and use an intertopic distance map to discern the variation in themes across different Reddit categories. In addition, we analyze the sentiment of the Reddit postings using Valence Aware Dictionary and Sentiment Reasoner to deduce the degree of negative, positive, and neutral sentiment of the discussion posts. Our findings reveal that the topics that caregivers most frequently discuss and seek advice for were related to caregiver stories, community support, and concerns ADRD. Specifically, we aimed to reproduce an organic Reddit search of caregiving of abuse on family member, financial struggles, symptoms of hallucinations, and repetition in ADRD family members. These results underscore the importance of online communities for gaining a comprehensive understanding of the multifaceted experiences and challenges faced by ADRD caregivers.

BACKGROUND: During the COVID-19 pandemic, patients with Alzheimer\'s disease and related dementias (ADRD) were especially vulnerable, and modes of medical care delivery shifted rapidly. This study assessed the impact of the pandemic on care for people with ADRD, examining the use of primary, emergency, and long-term care, as well as deaths due to COVID and to other causes.
METHODS: Among 4.2 million beneficiaries aged 66 and older with ADRD in traditional Medicare, monthly deaths and claims for routine care (doctors\' office and telehealth visits), inpatient/emergency department (ED) visits, and long-term care facility use from March or June 2020 through December 2022 are compared to monthly rates predicted from January-December 2019 using OLS and logistic/negative binomial regression. Correlation analyses examine the association between excess deaths - due to COVID and non-COVID causes - and changes in care use in the beneficiary\'s state of residence.
RESULTS: Increased telehealth visits more than offset reduced office visits, with primary care visits increasing overall (by 9 percent from June 2020 onward relative to the predicted rate from 2019, p < .001). Emergency/inpatient visits declined (by 9 percent, p < .001) and long-term care facility use declined, remaining 14% below the 2019 trend from June 2020 onward (p < .001). Both COVID and non-COVID deaths rose, with 231,000 excess deaths (16% above the prediction from 2019), over 80 percent of which were attributable to COVID. Excess deaths were higher among women, non-White patients, those in rural and isolated zip codes, and those with higher social deprivation index scores. States with the largest increases in primary care visits had the lowest excess deaths (correlation -0.49).
CONCLUSIONS: Older adults with ADRD had substantial deaths above pre-pandemic projections during the COVID-19 pandemic, 80 percent of which were attributed to COVID-19. Routine care increased overall due to a dramatic increase in telehealth visits, but this was uneven across states, and mortality rates were significantly lower in states with higher than pre-pandemic visits.

Background: The VALCODIS (Valencian Cognitive Diseases Study) cohort was designed and studied at the Hospital Universitari i Politècnic La Fe (Valencia, Spain) for the research of cognitive diseases, especially in the search for new biomarkers of Alzheimer\'s disease (AD). Methods: Participants in the VALCODIS cohort had cerebrospinal fluid (CSF) and blood samples, neuroimaging, and neuropsychological tests. The ApoE genotype was evaluated to identify its relationship with CSF biomarkers and neuropsychological tests in AD and non-AD participants. Results: A total of 1249 participants were included. They were mainly AD patients (n = 547) but also patients with other dementias (frontotemporal lobar dementia (n = 61), Lewy body dementia without AD CSF signature (n = 10), vascular dementia (n = 24) and other specific causes of cognitive impairment (n = 442), and patients with subjective memory complaints (n = 165)). In the ApoE genotype evaluation, significant differences were found for Aβ42 levels between genotypes in both AD and non-AD patients, as well as a negative correlation between tau values and a cognitive test in non-carriers and ε4 heterozygous. Conclusions: The VALCODIS cohort provides biologically diagnosed patients with demographical, clinical and biochemical data, and biological samples for further studies on early AD diagnosis. Also, the ApoE genotype evaluation showed correlations between CSF biomarkers and neuropsychological tests.

UNASSIGNED: Drug development for Alzheimer\'s disease has one of the greatest failure rates of any therapeutic field and AD is still incurable. Glycogen synthase kinase-3β is a critical enzyme implicated in the pathogenesis of AD, particularly in the hyperphosphorylation of tau protein, which leads to the formation of neurofibrillary tangles. TNF-α also plays a significant role in the pathogenesis of Alzheimer\'s disease by promoting neuroinflammation, contributing to the formation of amyloid plaques and neurofibrillary tangles, impairing synaptic function, and disrupting the balance of neurotrophic factors. Phytomedicine has numerous advantages over synthetic medications, acting multiple mode of action, including being less toxic and having fewer adverse effects. Flavonoids act as a promising therapeutic target for treating Alzheimer\'s disease. The present work investigates the anti-AD potentials of 35 flavonoids for the inhibition of GSK-3β and TNF-α.
UNASSIGNED: The physicochemical, pharmacokinetic parameters, toxicity profile and drug-likeliness of the selected 35 flavonoids were predicted using SwissADME & OSIRIS data Warrier property explorer web tool. All flavonoids were selected for docking studies on GSK-3β and TNF-α protein using Autodock 4.2.1.
UNASSIGNED: The predictions of this study suggested that among the selected 35 flavonoids, Top 3 flavonoids, such as Epicatechin gallate -10.93 kcal/mol, Fisetin -9.44 kcal/mol and Eriodictyol -8.54 kcal/mol for GSK-3β targets. TNF-α Fisetin -11.52 kcal/mol, Sterubin -10.87 kcal/mol, Biochainin A -10.69 kcal/mol were compared with standard drug donepezil.
UNASSIGNED: Therefore, these flavonoids could be utilized as possible leads for the structure-based design in the advancement of new, strong Anti-Alzheimer\'s agents. However, more invitro and invivo analyses are required to finally confirm the outcomes of this research.

Single Nucleotide Polymorphisms (SNPs) are key in understanding complex diseases. Nonsynonymous single-nucleotide polymorphisms (nsSNPs) occur in protein-coding regions, potentially altering amino acid sequences, protein structure and function. Computational methods are vital for distinguishing deleterious nsSNPs from neutral ones. We investigated the role of NLRP3 gene in neuroinflammation associated with Alzheimer\'s disease (AD) pathogenesis. A total of 893 missense (nsSNPs) were obtained from the dbSNP database and subjected to rigorous filtering using bioinformatics tools like SIFT, Align GVGD, PolyPhen-2, and PANTHER to identify potentially damaging variants. Of these, 18 nsSNPs were consistently predicted to have deleterious effects across all tools. Notably, 16 of these variants exhibited reduced protein stability, while only 4 were predicted to be buried within the protein structure. Among the identified nsSNPs, rs180177442 (R262L and R262P), rs201875324 (T659I), and rs139814109 (T897M) were classified as high-risk variants due to their significant deleterious impact, probable damaging effects, and association with decreased protein stability. Molecular docking and simulation analyses were conducted utilizing Memantine, a standard drug utilized in AD treatment, to investigate potential interactions with the altered protein structures. Additional clinical and genetic investigations are necessary to elucidate the underlying mechanisms that link NLRP3 polymorphisms with the initiation of AD.

UNASSIGNED: This study aimed to evaluate the effects of a multicomponent psychotherapy programme for people with mild Alzheimer\'s dementia (AD) and their caregivers on depression and related neuropsychiatric symptoms.
UNASSIGNED: The cognitive behavioural therapy (CBT)-based treatment consisted of 25 weekly sessions, including behavioural activation, behaviour management, interventions for the caregiver, reminiscence, couples counselling, and cognitive restructuring. 41 participants and their caregivers were randomised to either the CBT or the control group, which received treatment-as-usual (TAU). Follow-ups took place at 6 and 12 months posttreatment. The primary outcome was depression in the patient with AD. The secondary outcomes were apathy, other neuropsychiatric symptoms, functional abilities, quality of life, and quality of the relationship with the caregiver.
UNASSIGNED: Linear mixed models revealed a statistically significant superiority of CBT regarding clinician-rated depression at the 12-month follow-up with large effect sizes (within-subject d = 1.22, between-subject d = 1.00). Effect sizes were only moderate for self-rated depression and small for informant-rated depression. There was also a significant advantage for CBT regarding clinician-rated apathy, relationship quality, and informant-rated quality of life (QoL) but not for the other neuropsychiatric symptoms or self-rated QoL.
UNASSIGNED: The results are very encouraging and support an adequately powered multicentre study.
Trial registration: ClinicalTrials.gov NCT01273272. Date of registration: 3 Jan 2011.

Various oligomeric species of amyloid-beta have been proposed to play different immunogenic roles in the cellular pathology of Alzheimer\'s Disease. The dynamic interconversion between various amyloid oligomers and fibrillar assemblies makes it difficult to elucidate the role each potential aggregation state may play in driving neuroinflammatory and neurodegenerative pathology. The ability to identify the amyloid species that are key and essential drivers of these pathological hallmarks of Alzheimer\'s Disease is of fundamental importance for also understanding downstream events including tauopathies that mediate neuroinflammation with neurologic deficits. Here, we report the design and construction of a quantum dot mimetic for larger spherical oligomeric amyloid species as an \"endogenously\" fluorescent proxy for this cytotoxic assembly of amyloid to investigate its role in inducing inflammatory and stress response states in neuronal and glial cell types. The design parameters and construction protocol developed here may be adapted for developing quantum dot nano-bio assemblies for other biological systems of interest, particularly neurodegenerative diseases involving other protein aggregates.

Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [MeanAGE = 72.69 (5.48)] with menarche in childhood, early-, mid-, and late-adolescence and dementia prevalence, severity, and type, including the effects of education and socioeconomic status. Adjusting for covariates, menarche at 11-14 years of age was associated with better memory, executive and global cognitive functioning in old age, and stronger positive effects of education and socioeconomic status on cognition than those with menarche at 15-17 years. We found a critical age window for the neuroprotective effects of estrogens during early adolescence, putting women with later menarche at higher risk for cognitive decline. Effects of socioeconomic status and education in adulthood should be a focus of future research.

Criticality, observed during second-order phase transitions, is an emergent phenomenon. The brain operates near criticality where complex systems exhibit high correlations. As a system approaches criticality, it develops \"domain\"-like regions with competing phases and increased spatio-temporal correlations that diverge. The dynamics of these domains depend on the system\'s proximity to criticality. This study explores the differences in the proximity to criticality of Alzheimer\'s-afflicted and cognitively normal brains through the use of a spin-lattice model derived from resting-state fMRI data and investigates the type of criticality found in the human brain - whether it is of the Ising class or something more complex. The temporal correlations in both groups display a stretched exponential nature, indicating closer alignment with the criticality of the spin-glass class rather than the Ising class. Longer relaxation times observed in cognitively normal subjects suggest increased proximity to the phase boundary. The weak distinction observed in the spatial characteristics related to proximity to criticality might once more point to a spin-glass scenario, necessitating nuanced order parameters to distinguish between phase-ordering in Alzheimer\'s and cognitively normal brains.

BACKGROUND: The link between Alzheimer\'s disease and depression has been confirmed by clinical and epidemiological research. Therefore, our study examined the literary landscape and prevalent themes in depression-related research works on Alzheimer\'s disease through bibliometric analysis.
METHODS: Relevant literature was identified from the Web of Science core collection. Bibliometric parameters were extracted, and the major contributors were defined in terms of countries, institutions, authors, and articles using Microsoft Excel 2019 and VOSviewer. VOSviewer and CiteSpace were employed to visualize the scientific networks and seminal topics.
RESULTS: The analysis of literature utilised 10,553 articles published from 1991 until 2023. The three countries or regions with the most publications were spread across the United States, China, and England. The University of Toronto and the University of Pittsburgh were the major contributors to the institutions. Lyketsos, Constantine G., Cummings, JL were found to make outstanding contributions. Journal of Alzheimer\'s Disease was identified as the most productive journal. Furthermore, \"Alzheimer\'s\", \"depression\", \"dementia\", and \"mild cognitive decline\" were the main topics of discussion during this period.
CONCLUSIONS: Data were searched from a single database to become compatible with VOSviewer and CiteSpace, leading to a selection bias. Manuscripts in English were considered, leading to a language bias.
CONCLUSIONS: Articles on \"Alzheimer\'s\" and \"depression\" displayed an upward trend. The prevalent themes addressed were the mechanisms of depression-associated Alzheimer\'s disease, the identification of depression and cognitive decline in the early stages of Alzheimer\'s, alleviating depression and improving life quality in Alzheimer\'s patients and their caregivers, and diagnosing and treating neuropsychiatric symptoms in Alzheimer. Future research on these hot topics would promote understanding in this field.