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The aggregation of Amyloid- β (A β) peptides is associated with neurodegeneration in Alzheimer's disease (AD). We previously identified novel naphtalene derivatives, including the lead compound Amylovis-201, able to form thermodynamically stable complexes with A β species, peptides and fibrils. As the drug showed a chemical scaffold coherent for an effective interaction with the σ 1 receptor chaperone and as σ 1 agonists are currently developed as potent neuroprotectants in AD, we investigated the pharmacological action of Amylovis-201 on the σ 1 receptor. We report that Amylovis-201 is a potent σ 1 agonist by several in silico , in vitro and in vivo assays and that its anti-amnesic and neuroprotective effects involve a pharmacological action at σ 1 receptors. Furthermore, we show for the first time that classical σ 1 receptor agonist (PRE-084), and antagonist (NE-100) are able to interact and disaggregate A β 25–35 fibrils. Interestingly, Amylovis-201 was the only compound inhibiting A β 25–35 aggregates formation. Our results therefore highlight a dual action of Amylovis-201 as anti-aggregating agent and σ 1 receptor agonist that could be highly effective in long-term treatment against neurodegeneration in AD. Amylovis-201, known to interfere with Amyloid- β aggregation, also acts as a sigma-1 agonist in vitro and in vivo. The drug is therefore a dual-acting compound with synergic extracellular and intracellular modes of action. [Display omitted] [ABSTRACT FROM AUTHOR]

INTRODUCTION: Magnetic resonance imaging (MRI) segmentation algorithms make it possible to study detailed medial temporal lobe (MTL) substructures as hippocampal subfields and amygdala subnuclei, offering opportunities to develop biomarkers for preclinical Alzheimer's disease (AD). METHODS: We identified the MTL substructures significantly associated with tau‐positron emission tomography (PET) signal in 581 non‐demented individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI‐3). We confirmed our results in our UCLouvain cohort including 110 non‐demented individuals by comparing volumes between individuals with different visual Braak's stages and clinical diagnosis. RESULTS: Four amygdala subnuclei (cortical, central, medial, and accessory basal) were associated with tau in amyloid beta‐positive (Aβ+) clinically normal (CN) individuals, while the global amygdala and hippocampal volumes were not. Using UCLouvain data, we observed that both Braak I‐II and Aβ+ CN individuals had smaller volumes in these subnuclei, while no significant difference was observed in the global structure volumes or other subfields. CONCLUSION: Measuring specific amygdala subnuclei, early atrophy may serve as a marker of temporal tauopathy in preclinical AD, identifying individuals at risk of progression. Highlights: Amygdala atrophy is not homogeneous in preclinical Alzheimer's disease (AD).Tau pathology is associated with atrophy of specific amygdala subnuclei, specifically, the central, medial, cortical, and accessory basal subnuclei.Hippocampal and amygdala volume is not associated with tau in preclinical AD.Hippocampus and CA1‐3 volume is reduced in preclinical AD, regardless of tau. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Multi‐omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS: To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP‐AD) expanded brain multi‐omics profiling to multi‐ethnic donors. RESULTS: We generated multi‐omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non‐Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION: The inclusion of traditionally underrepresented groups in multi‐omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD. Highlights: Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi‐ethnic populations.Brain multi‐omics data is generated from Black American, Latin American, and non‐Hispanic White donors.RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared.Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The relationship between cerebrovascular disease (CVD) and amyloid beta (Aβ) in Alzheimer's disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)–based CVD biomarkers—including cerebral microbleeds (CMBs), lacunar infarction, and white matter hyperintensities (WMHs)—would correlate with Aβ positivity on positron emission tomography (Aβ‐PET). METHODS: We cross‐sectionally analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 1352). Logistic regression was used to calculate odds ratios (ORs), with Aβ‐PET positivity as the standard‐of‐truth. RESULTS: Following adjustment, WMHs (OR = 1.25) and superficial CMBs (OR = 1.45) remained positively associated with Aβ‐PET positivity (p < 0.001). Deep CMBs and lacunes exhibited a varied relationship with Aβ‐PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ‐PET (pseudo‐R2 = 0.41). DISCUSSION: The study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria. ClinicalTrials.gov: ADNI‐2 (NCT01231971), ADNI‐3 (NCT02854033). Highlights: Cerebrovascular biomarkers linked to amyloid beta (Aβ) in Alzheimer's disease (AD).White matter hyperintensities and cerebral microbleeds reliably predict Aβ‐PET positivity.Relationships with Aβ‐PET vary by cognitive stage.Novel accessible model predicts Aβ‐PET status.Study supports multimodal diagnostic approaches. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid (CSF) biomarkers for AD‐related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF β‐amyloid‐42/40, neurofilament light chain (NfL), and phospho‐tau‐181(p‐tau181)/β‐amyloid‐42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease‐relevant groups that correlate with biopsy data. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking. Highlights: AD CSF biomarkers correlate with CNS pathology and transcriptomic changes.Seven proteins correlate with CNS pathology and gene expression changes.Inflammatory and neuronal gene expression changes correlate with YKL‐40 and NPTXR, respectively.CSF metabolomic analysis identifies pathways that correlate with biopsy data.Fatty acid metabolic pathways correlate with β‐amyloid pathology. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We used clinical assessment records to provide pan‐Canadian estimates of the prevalence and risks associated with recent (within the last 3 days) critical wandering among home care clients, with and without dementia. METHODS: The data source is interRAI Home Care (interRAI HC) assessments. The population was all long‐stay home care clients assessed between 2004 and 2021 in seven Canadian provinces and territories (N = 1,598,191). We tested associations between wandering and cognition and dementia diagnoses using chi‐square tests and logistic regression. RESULTS: Approximately 84% of the sample was over the age of 65. The overall rate of recent wandering was 3.0%. Dementia diagnosis was strongly associated with two to four times higher rates in the prevalence of recent critical wandering. DISCUSSION: InterRAI HC offers insights into the wandering risk of home care clients. This information should be used to manage risks in the community and could be shared with first responders. Highlights: In all the study regions combined, the rate of recent wandering is 3.0%.Dementia was associated with 18 times greater prevalence of recent critical wandering.Home care clients at risk of wandering have complex clinical profiles that pose important risks for their health and well‐being.Collaboration and information sharing between search and rescue and health professions is essential for managing risks related to critical wandering. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate‐weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high‐resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex‐specific manner. METHODS: Eight‐month‐old male and female AD mice harboring mutant amyloid precursor protein (APPNL‐F/NL‐F: n = 36) and wild‐type (WT: n = 39) mice underwent GluCEST MRI, followed by proton magnetic resonance spectroscopy (1H‐MRS) in hippocampus and thalamus/hypothalamus using 9.4T preclinical MR scanner. RESULTS: GluCEST measurements revealed significant (p ≤ 0.02) glutamate loss in the entorhinal cortex (% change ± standard error: 8.73 ± 2.12%), hippocampus (11.29 ± 2.41%), and hippocampal fimbriae (19.15 ± 2.95%) of male AD mice. A similar loss of hippocampal glutamate in male AD mice (11.22 ± 2.33%; p = 0.01) was also observed in 1H‐MRS. DISCUSSIONS: GluCEST MRI detected glutamate reductions in the fimbria and entorhinal cortex of male AD mice, which was not reported previously. Resilience in female AD mice against these changes indicates an intact status of cerebral energy metabolism. Highlights: Glutamate levels were monitored in different brain regions of early‐stage Alzheimer's disease (AD) and wild‐type male and female mice using glutamate‐weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI). Male AD mice exhibited significant glutamate loss in the hippocampus, entorhinal cortex, and the fimbriae of the hippocampus. Interestingly, female AD mice did not have any glutamate loss in any brain region and should be investigated further to find the probable cause. These findings demonstrate previously unreported sex‐specific glutamate changes in hippocampal sub‐regions using high‐resolution GluCEST MRI. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The molecular basis of cognitive resilience (CR) among pathologically confirmed Alzheimer's disease (AD) cases is not well understood. METHODS: Abundance of 13 cell types and neuronal subtypes in brain bulk RNA‐seq data from the anterior caudate, dorsolateral prefrontal cortex (DLPFC), and posterior cingulate cortex (PCC) obtained from 434 AD cases, 318 cognitively resilient AD cases, and 188 controls in the Religious Orders Study and Rush Memory and Aging Project was estimated by deconvolution. RESULTS: PVALB+ neuron abundance was negatively associated with cognitive status and tau pathology in the DLPFC and PCC (Padj < 0.001) and the most reduced neuronal subtype in AD cases compared to controls in DLPFC (Padj = 8.4 × 10−7) and PCC (Padj = 0.0015). We identified genome‐wide significant association of neuron abundance with TMEM106B single nucleotide polymorphism rs13237518 in PCC (p = 6.08 × 10−12). rs13237518 was also associated with amyloid beta (p = 0.0085) and tangles (p = 0.0073). DISCUSSION: High abundance of PVALB+ neurons may be a marker of CR. TMEM106B variants may influence CR independent of AD pathology. Highlights: Neuron retention and a lack of astrocytosis are highly predictive of Alzheimer's disease (AD) resilience.PVALB+ GABAergic and RORB+ glutamatergic neurons are associated with cognitive status.A TMEM106B single nucleotide polymorphism is related to lower AD risk, higher neuron count, and increased AD pathology. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Recent advances in biomarker research have improved the diagnosis and monitoring of Alzheimer's disease (AD), but in vivo biomarker‐based workflows to assess 4R‐tauopathy (4RT) patients are currently missing. We suggest a novel biomarker‐based algorithm to characterize AD and 4RTs. METHODS: We cross‐sectionally assessed combinations of cerebrospinal fluid measures (CSF p‐tau181 and t‐tau) and 18F‐PI‐2620 tau‐positron emission tomography (PET) in patients with AD (n = 64), clinically suspected 4RTs (progressive supranuclear palsy or corticobasal syndrome, n = 82) and healthy controls (n = 19). RESULTS: Elevated CSF p‐tau181 and cortical 18F‐PI‐2620 binding was characteristic for AD while normal CSF p‐tau181 with elevated subcortical 18F‐PI‐2620 binding was characteristic for 4RTs. 18F‐PI‐2620‐assessed posterior cortical hypoperfusion could be used as an additional neuronal injury biomarker in AD. DISCUSSION: The specific combination of CSF markers and 18F‐PI‐2620 tau‐PET in disease‐specific regions facilitates the biomarker‐guided stratification of AD and 4RTs. This has implications for biomarker‐aided diagnostic workflows and the advancement in clinical trials. Highlights: Novel biomarker‐based algorithm for differentiating AD and 4R‐tauopathies.A combination of CSF p‐tau181 and 18F‐PI‐2620 discriminates AD versus 4R tauopathies.Hypoperfusion serves as an additional neuronal injury biomarker in AD. [ABSTRACT FROM AUTHOR]

Neurogenesis persists throughout adulthood in the hippocampus and contributes to specific cognitive functions. In Alzheimer's disease (AD), the hippocampus is affected by pathology and functional impairment early in the disease. Human AD patients have reduced adult hippocampal neurogenesis (AHN) levels compared to age‐matched healthy controls. Similarly, rodent AD models show a decrease in AHN before the onset of the classical hallmarks of AD pathology. Conversely, enhancement of AHN can protect against AD pathology and ameliorate memory deficits in both rodents and humans. Therefore, impaired AHN may be a contributing factor of AD‐associated cognitive decline, rather than an effect of it. In this review we outline the regulation and function of AHN in healthy individuals, and highlight the relationship between AHN dysfunction and cognitive impairments in AD. The existence of AHN in humans and its relevance in AD patients will also be discussed, with an outlook toward future research directions. Highlights: Adult hippocampal neurogenesis occurs in the brains of mammals including humans.Adult hippocampal neurogenesis is reduced in Alzheimer's disease in humans and animal models. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The spatial and temporal patterns of cortical mean diffusivity (cMD), as well as its association with Alzheimer's disease (AD) and suspected non‐Alzheimer's pathophysiology (SNAP), are not yet fully understood. METHODS: We compared baseline (n = 617) and longitudinal changes (n = 421) of cMD, cortical thickness, and gray matter volume and their relations to vascular risk factors, amyloid beta (Aβ), and tau positron emission tomography (PET), and longitudinal cognitive decline in Aβ PET negative and positive older adults. RESULTS: cMD increases were more sensitive to detecting brain structural alterations than cortical thinning and gray matter atrophy. Tau‐related cMD increases partially mediated Aβ‐related cognitive decline in AD, whereas vascular disease‐related increased cMD levels substantially mediated age‐related cognitive decline in SNAP. DISCUSSION: These findings revealed the dynamic changes of microstructural and macrostructural indicators and their associations with AD and SNAP, providing novel insights into understanding upstream and downstream events of cMD in neurodegenerative disease. Highlights: Cortical mean diffusivity (cMD) was more sensitive to detecting structural changes than macrostructural factors.Tau‐related cMD increases partially mediated amyloid beta–related cognitive decline in Alzheimer's disease (AD).White matter hyperintensity–related higher cMD mainly explained the age‐related cognitive decline in suspected non‐Alzheimer's pathophysiology (SNAP).cMD may assist in tracking earlier neurodegenerative signs in AD and SNAP. [ABSTRACT FROM AUTHOR]

Black women are sorely underrepresented in studies of Alzheimer's disease and related dementias (ADRD) despite higher rates of ADRD diagnoses than in non‐Hispanic White women. There are many reasons for underrepresentation, including medical mistrust, limited access to clinical studies, and restrictive study inclusion criteria. These pervasive barriers to research participation are often not considered during study development and, if eventually thought of tend to be after the fact. Community‐engaged research (CER) approaches are an effective method for reducing participation barriers. This article describes how CER approaches were used to develop the Black Women Inflammation and Tau Study (BWITS), a prospective study to identify biopsychosocial risk factors for ADRD in Black women. Guidelines discussed here for future ADRD research in diverse populations are informed by Community‐Based Participatory Research (CBPR), the National Institute on Minority Health and Health Disparities (NIMHD), and the Patient‐Centered Outcomes Research Institute (PCORI). Highlights: Understand the historical tragedies related to medical practices and research designs that may contribute to the underrepresentation of Black Americans in research studies today.Highlight community‐engaged research approaches that effectively reduce participation barriers in minoritized groups.Review Community‐Based Participatory Research, National Institute of Minority Health and Health Disparities, and the Patient‐Centered Outcomes Research Institute guidelines for conducting research with minoritized communities.Describe using the three frameworks to inform the study development protocol for the Black Women Inflammation and Tau Study.Conclude by offering study design considerations that we hope can be a helpful starting point for others conducting research with minoritized communities. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Neuroanatomical normative modeling captures individual variability in Alzheimer's disease (AD). Here we used normative modeling to track individuals' disease progression in people with mild cognitive impairment (MCI) and patients with AD. METHODS: Cortical and subcortical normative models were generated using healthy controls (n ≈ 58k). These models were used to calculate regional z scores in 3233 T1‐weighted magnetic resonance imaging time‐series scans from 1181 participants. Regions with z scores < –1.96 were classified as outliers mapped on the brain and summarized by total outlier count (tOC). RESULTS: tOC increased in AD and in people with MCI who converted to AD and also correlated with multiple non‐imaging markers. Moreover, a higher annual rate of change in tOC increased the risk of progression from MCI to AD. Brain outlier maps identified the hippocampus as having the highest rate of change. DISCUSSION: Individual patients' atrophy rates can be tracked by using regional outlier maps and tOC. Highlights: Neuroanatomical normative modeling was applied to serial Alzheimer's disease (AD) magnetic resonance imaging (MRI) data for the first time.Deviation from the norm (outliers) of cortical thickness or brain volume was computed in 3233 scans.The number of brain‐structure outliers increased over time in people with AD.Patterns of change in outliers varied markedly between individual patients with AD.People with mild cognitive impairment whose outliers increased over time had a higher risk of progression from AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. METHODS: MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p‐tau181, amyloid beta 1‐42 [Aβ1‐42], Aβ1‐40) were analyzed using logistic and analysis of covariance models. RESULTS: Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p = 0.023) and lower CSF Aβ1‐42 (p = 0.047), Aβ1‐42/Aβ1‐40 (p = 0.040), and Aβ1‐42/p‐tau181 (p = 0.020) in the whole cohort. DISCUSSION: Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients. Highlights: We studied the impact of caffeine consumption in the BALTAZAR cohort.Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients.Caffeine intake is associated with CSF biomarkers in AD patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Mnemonic Similarity Task (MST) is a popular memory task designed to assess hippocampal integrity. We assessed whether analyzing MST performance using a multinomial processing tree (MPT) cognitive model could detect individuals with elevated Alzheimer's disease (AD) biomarker status prior to cognitive decline. METHOD: We analyzed MST data from >200 individuals (young, cognitively healthy older adults and individuals with mild cognitive impairment [MCI]), a subset of which also had existing cerebrospinal fluid (CSF) amyloid beta (Aβ) and phosphorylated tau (pTau) data using both traditional and model‐derived approaches. We assessed how well each could predict age group, memory ability, MCI status, Aβ, and pTau status using receiver operating characteristic analyses. RESULTS: Both approaches predicted age group membership equally, but MPT‐derived metrics exceeded traditional metrics in all other comparisons. DISCUSSION: A MPT model of the MST can detect individuals with AD prior to cognitive decline, making it a potentially useful tool for screening and monitoring older adults during the asymptomatic phase of AD. Highlights: The MST, along with cognitive modeling, identifies individuals with memory deficits and cognitive impairment.Cognitive modeling of the MST identifies individuals with increased AD biomarkers prior to changes in cognitive function.The MST is a digital biomarker that identifies individuals at high risk of AD. [ABSTRACT FROM AUTHOR]

The Alzheimer's Disease Neuroimaging Initiative (ADNI) PET Core has evolved over time, beginning with positron emission tomography (PET) imaging of a subsample of participants with [18F]fluorodeoxyglucose (FDG)‐PET, adding tracers for measurement of β‐amyloid, followed by tau tracers. This review examines the evolution of the ADNI PET Core, the novel aspects of PET imaging in each stage of ADNI, and gives an accounting of PET images available in the ADNI database. The ADNI PET Core has been and continues to be a rich resource that provides quantitative PET data and preprocessed PET images to the scientific community, allowing interrogation of both basic and clinically relevant questions. By standardizing methods across different PET scanners and multiple PET tracers, the Core has demonstrated the feasibility of large‐scale, multi‐center PET studies. Data managed and disseminated by the PET Core has been critical to defining pathophysiological models of Alzheimer's disease (AD) and helped to drive methods used in modern therapeutic trials. Highlights: The ADNI PET Core began with FDG‐PET and now includes three amyloid and three tau PET ligands.The PET Core has standardized acquisition and analysis of multitracer PET images.The ADNI PET Core helped to develop methods that have facilitated clinical trials in AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Typical Alzheimer's disease (AD) and limbic‐predominant age‐related TAR DNA‐binding protein 43 (TDP‐43) encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but are associated with distinct proteinopathies. METHODS: We investigated white matter (WM) fiber bundle alterations, using fixel‐based analysis, a state‐of‐the‐art diffusion magnetic resonance imaging model, in early AD, presumed LATE, and controls. We also investigated regional cortical atrophy. RESULTS: Both amnestic AD and presumed LATE patients exhibited WM alterations in tracts of the temporal and limbic lobes and in callosal fibers connecting superior frontal gyri. In addition, presumed LATE patients showed alterations in callosal fibers connecting the middle frontal gyri and in the cerebello–thalamo–cortical tract. Cortical thickness was reduced in regions connected by the most altered tracts. DISCUSSION: These findings, the first to describe WM fiber bundle alterations in presumed LATE, are consistent with results on cortical atrophy and with the staging system of tau or TDP‐43 accumulation. Highlights: Fixel‐based analysis revealed white matter (WM) fiber bundle alterations in presumed limbic‐predominant age‐related TAR DNA‐binding protein 43 encephalopathy (LATE) patients identified by isolated episodic/limbic amnesia, the absence of positive Alzheimer's disease (AD) biomarkers, and no other neurological diagnosis after 2 years of follow‐up.Presumed LATE and amnestic AD shared similar patterns of WM alterations in fiber bundles of the limbic and temporal lobes, in congruence with their similar limbic cognitive phenotype.Presumed LATE differed from AD by the alteration of the callosal fibers connecting the middle frontal gyri and of the cerebello–thalamo–cortical tract.WM fiber bundle alterations were consistent with results on regional cortical atrophy.The different anatomical patterns of WM degeneration could provide information on the propagation pathways of distinct proteinopathies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Digital cognitive assessments, particularly those that can be done at home, present as low‐burden biomarkers for participants and patients alike, but their effectiveness in the diagnosis of Alzheimer's disease (AD) or predicting its trajectory is still unclear. Here, we assessed what utility or added value these digital cognitive assessments provide for identifying those at high risk of cognitive decline. METHODS: We analyzed >500 Alzheimer's Disease Neuroimaging Initiative participants who underwent a brief digital cognitive assessment and amyloid beta (Aβ)/tau positron emission tomography scans, examining their ability to distinguish cognitive status and predict cognitive decline. RESULTS: Performance on the digital cognitive assessment was superior to both cortical Aβ and entorhinal tau in detecting mild cognitive impairment and future cognitive decline, with mnemonic discrimination deficits emerging as the most critical measure for predicting decline and future tau accumulation. DISCUSSION: Digital assessments are effective at identifying at‐risk individuals, supporting their utility as low‐burden tools for early AD detection and monitoring. Highlights: Performance on digital cognitive assessments predicts progression to mild cognitive impairment at a higher proficiency compared to amyloid beta and tau.Deficits in mnemonic discrimination are indicative of future cognitive decline.Impaired mnemonic discrimination predicts future entorhinal and inferior temporal tau. [ABSTRACT FROM AUTHOR]

INTRODUCTION: CT1812 is in clinical development for the treatment of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) exploratory proteomics was employed to identify pharmacodynamic biomarkers of CT1812 in mild to moderate AD from two independent clinical trials. METHODS: Unbiased analysis of tandem‐mass tag mass spectrometry (TMT‐MS) quantitative proteomics, pathway analysis and correlation analyses with volumetric magnetic resonance imaging (vMRI) were performed for the SPARC cohort (NCT03493282). Comparative analyses and a meta‐analysis with the interim SHINE cohort (NCT03507790; SHINE‐A) followed by network analysis (weighted gene co‐expression network analysis [WGCNA]) were used to understand the biological impact of CT1812. RESULTS: CT1812 pharmacodynamic biomarkers and biological pathways were identified that replicate across two clinical cohorts. The meta‐analysis revealed novel candidate biomarkers linked to S2R biology and AD, and network analysis revealed treatment‐associated networks driven by S2R. DISCUSSION: Early clinical validation of CT1812 candidate biomarkers replicating in independent cohorts strengthens the understanding of the biological impact of CT1812 in patients with AD, and supports CT1812's synaptoprotective mechanism of action and its continued clinical development. Highlights: This exploratory proteomics study identified candidate biomarkers of CT1812 in SPARC (NCT03493282)Comparative analyses identified biomarkers replicating across trials/cohortsTwo independent Ph2 trial cohorts (SPARC and interim SHINE [NCT03507790; SHINE‐A]) were used in a meta‐analysisAmyloid beta (Aβ) & synaptic biology impacted by CT1812 and volumetric magnetic resonance imaging (vMRI) treatment‐related correlates emergeNetwork analyses revealed sigma‐2 receptor (S2R)‐interacting proteins that may be "drivers" of changes [ABSTRACT FROM AUTHOR]

INTRODUCTION: The in vivo detection of mixed Alzheimer's disease (AD) and α‐synuclein (αSyn) pathology is important for clinical management and prognostic stratification. We investigated the contribution of αSyn pathology, detected by cerebrospinal fluid (CSF) seed amplification assay (αSyn SAA), on [18F]‐fluorodeoxyglucose positron emission tomography (FDG PET) pattern in subjects with amnestic mild cognitive impairment (aMCI). METHODS: We included 562 aMCI participants and 204 cognitively normal controls (CN) with available αSyn SAA and cerebral metabolic rate for glucose utilization (rCMRgl) data. RESULTS: 24% of aMCI cases were positive (+) for CSF αSyn SAA. Compared to CN, both αSyn+ and negative (−) aMCI participants showed reductions in rCMRgl within AD typical regions. αSyn+ aMCI had lower rCMRgl within AD and dementia with Lewy bodies (DLB) typical regions compared to αSyn− aMCI, even after stratification according to the CSF AT(N) system. DISCUSSION: αSyn pathology contributes to a distinct FDG PET pattern in aMCI. Highlights: αSyn pathology can be detected in vivo by CSF αSyn SAA.We investigated the FDG PET pattern in aMCI patients with CSF αSyn SAA positivity.αSyn+ aMCI showed a marked brain hypometabolism in AD and DLB typical regions. [ABSTRACT FROM AUTHOR]

The COVID pandemic has shown that when the research community comes together, we can conquer the most complex biomedical challenges. Collaboration and teamwork among federal agencies, private organizations, and researchers have been crucial in the development of vaccines and therapeutics against COVID. Possibly the first example of such cross‐functional collaboration is the Alzheimer's Disease Neuroimaging Initiative (ADNI), the largest and longest continually monitored Alzheimer's study. ADNI was designed and operated as a public‐private partnership, managed by the Foundation for the National Institutes of Health. This article shows how recent successes in the Alzheimer's field are directly a result of ADNI's open and transparent sharing of knowledge, expertise, and resources, which have allowed researchers to advance their understanding of Alzheimer's and tackle challenges in a relatively short period of time. ADNI's approach to open‐source innovation also served as a model for addressing other complex diseases and led to numerous collaborative research initiatives. Highlights: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was designed, structured, and operated as a public‐private partnership, managed by the Foundation for the National Institutes of Health.The recent successes in the Alzheimer's field are directly a result of ADNI's efforts.Open and transparent sharing of knowledge, expertise, and resources allowed researchers to advance their understanding of Alzheimer's and tackle challenges in a relatively short period of time. [ABSTRACT FROM AUTHOR]

A Nature Medicine paper published in January 2024 describes eight cases of iatrogenic Alzheimer's disease in individuals who received cadaveric pituitary‐derived human growth hormone. The paper's conclusions argue for the transmissibility of Alzheimer's disease, which, if true, would create a significant public health crisis. For example, neurosurgical practices would require substantial revision, and many individuals who have undergone neurosurgical procedures would now be at considerable risk of Alzheimer's disease. A detailed review of the presented cases reveals that they do not have Alzheimer's disease, and there are alternative explanations for the cognitive decline described. In people with progressive cognitive decline, the diagnosis of Alzheimer's disease requires a demonstration of amyloid and tau pathology or amyloid and tau biomarkers. Extensive tau pathology is not demonstrated, and some also lack amyloid beta pathology. The cases described in this paper do not meet the criteria for dementia due to Alzheimer's disease by clinical and pathological standards. Highlights: Creutzfeldt‐Jakob disease has been transmitted by cadaveric growth hormone.There is no evidence for the transmission of Alzheimer's disease by cadaveric growth hormone.There is no evidence that Alzheimer's disease is transmissible. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Cellular prion protein (PrPC) was implicated in amyloid beta (Aβ)‐induced toxicity in Alzheimer's disease (AD), but the precise molecular mechanisms involved in this process are unclear. METHODS: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light‐sheet microscopy was used for whole brain tissue analyses. PrPC‐overexpressing cells were developed for in vitro studies, and microscopy was used to assess co‐localization of proteins of interest. Surface‐plasmon resonance (SPR) was used to investigate protein‐binding characteristics. RESULTS: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aβ levels. Light‐sheet microscopy showed that PrPC influenced Aβ‐plaque burden but not the distribution of those plaques. Interestingly, caveolin‐1 (Cav‐1) KO neurons significantly reduced intracellular Aβ‐oligomer (Aβo) uptake when compared to wild‐type neurons. DISCUSSION: The findings shed new light on the relevance of intracellular Aβo, suggesting that PrPC and Cav‐1 modulate intracellular Aβ levels and the Aβ‐plaque load. Highlights: PrPC expression adversely affects lifespan and behavior in 5xFAD mice.PrPC increases Aβ1‐40 and Aβ1‐42 levels and Aβ‐plaque load in 5xFAD mice.Cav‐1 interacts with both PrPC and Aβ peptides.Knocking out Cav‐1 leads to a significant reduction in intracellular Aβ levels. [ABSTRACT FROM AUTHOR]

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has revolutionized the landscape of Alzheimer's research through its Informatics Core, which has facilitated unprecedented data standardization and sharing. Over 20 years, ADNI established a robust informatics framework, enabling the validation of biomarkers and supporting global research efforts. The Informatics Core, centered at the Laboratory of Neuro Imaging (LONI), provides a comprehensive data hub that ensures data quality, accessibility, and security, fostering over 5600 publications and significant scientific advancements. By embracing open data sharing principles, ADNI set a gold standard in data transparency, allowing over 26,000 investigators from 169 countries to access and download a wealth of multimodal data. This collaborative approach not only accelerated biomarker discovery and drug development and advanced our understanding of Alzheimer's disease but also has served as a model for other research initiatives, demonstrating the transformative potential of carefully designed informatics models and shared data in driving global scientific progress. Highlights: Accelerating biomarker discovery and drug development for Alzheimer's disease.Alzheimer's Disease Neuroimaging Initiative's (ADNI's) open data sharing drives scientific progress.Data exploration and coupled analytics to data archives. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive. METHODS: Here, we integrated [18F]FDG‐PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel‐wise linear regression analysis. RESULTS: Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG‐PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak‐t(223) = 4.86, P value < 0.001) and zinc‐finger–related regulatory units (peak‐t(223) = 3.90, P value < 0.001). DISCUSSION: By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity–associated genes and zinc‐finger–related regulatory units are highly associated with brain metabolic changes in AD. Highlights: We conducted an integrated analysis of system‐based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) at the voxel level in Alzheimer's disease (AD).The biological process of serine/threonine kinase activity was the most associated with [18F]FDG‐PET in the AD brain.Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG‐PET.Zinc‐finger transcription factor targets were associated with AD brain [18F]FDG‐PET metabolism. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Geographic variation in diagnosed cases of Alzheimer's disease and related dementias (ADRD) could be due to underlying population risk or differences in intensity of new case identification. Areas with low ADRD diagnostic intensity could be targeted for additional surveillance efforts. METHODS: Medicare claims were used for a cohort of older adults across hospital referral regions (HRRs). ADRD‐specific regional diagnosis intensity was measured as the ratio of expected new ADRD cases (estimated using population demographics, risk factors, and practice intensity) compared to observed ADRD‐diagnosed cases. RESULTS: Crude new ADRD diagnosis rate ranged from 1.7 to 5.4 per 100 across HRRs. ADRD‐specific diagnosis intensity ranged from 0.69 to 1.47 and varied most for Black, Hispanic, and the youngest (66–74) subgroups. Across all subgroups, ADRD diagnosis intensity was associated with 2‐fold difference in receiving an ADRD diagnosis. DISCUSSION: Where one resides influences the likelihood of receiving an ADRD diagnosis, particularly among those 66–74 years of age and minoritized groups. Highlights: Rate of new Alzheimer's disease and related dementias (ADRD) case identification varies geographically across the United States.Variation in case identification is greatest in Black, Hispanic, and young‐old groups.Intensity of diagnosis (ie, case identification) unrelated to population risk differs across place.Likelihood of receiving an ADRD diagnosis varies 2‐fold based on place of residence. [ABSTRACT FROM AUTHOR]

Biological and clinical heterogeneity is a major challenge in research for developing new treatments for Alzheimer's disease (AD). AD may be defined by its amyloid beta and tau pathologies, but we recognize that mixed pathologies are common, and that diverse genetics, central nervous system (CNS) and systemic pathophysiological processes, and environmental/experiential factors contribute to AD's diverse clinical and neuropathological features. All these factors are rational targets for therapeutic development; indeed, there are hundreds of candidate pharmacological, dietary, neurostimulation, and lifestyle interventions that show benefits in homogeneous laboratory models. Conventional clinical trial designs accommodate heterogeneity poorly, and this may be one reason that progress in translating candidate interventions has been so difficult. We review the challenges of AD's heterogeneity for the clinical trials enterprise. We then discuss how advances in repeatable biomarkers and digital phenotyping enable novel "single‐case" and adaptive trial designs to accelerate therapeutics development, moving us closer to personalized research and medicine for AD. Highlights: Alzheimer's disease is diverse in its clinical features, course, risks, and biology.Typical randomized controlled trials are exclusive and necessarily large to attain arm comparability with broad outcomes.Repeated blood biomarkers and digital tracking can improve outcome measure precision and sensitivity.This enables the use of novel "single‐case" and adaptive trial designs for inclusivity, rigor, and efficiency. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population. METHODS: This population‐based study used baseline data from MIND‐China (2018; n = 4873) and follow‐up data from dementia‐free individuals (2014–2018; n = 2117). We measured AD‐related plasma biomarkers in a subsample (n = 1256). Data were analyzed using logistic and Cox regression models. RESULTS: We developed PRS with (PRSAPOE) and without (PRSnon‐APOE) apolipoprotein E (APOE) gene. In the longitudinal analysis, PRSAPOE was associated with a multivariable‐adjusted hazards ratio of 1.91 (95% CI = 1.13–3.23) for AD. PRSAPOE in combination with demographics yielded discriminative (area under the curve [AUC]) and predictive(C‐statistic) accuracy of 0.80 (95% confidence interval [CI] = 0.77–0.84) and 0.80 (0.77–0.82), respectively. PRSnon‐APOE showed an association with AD risk similar to PRSAPOE. PRSAPOE, but not PRSnon‐APOE, was associated with reduced plasma Aβ42/Aβ40 ratio and increased Neurofilament light chain (NfL) (p < 0.05). DISCUSSION: The PRS with and without APOE gene, in combination with demographics, shows good discriminative and predictive ability for AD. The AD‐related pathologies underlie AD risk associated with PRSAPOE. Highlights: The PRSAPOE and PRSnon‐APOE were associated with AD risk in the Chinese population.The PRSAPOE and PRSnon‐APOE, in combination with demographics, showed good discriminative and predictive ability for AD.The AD‐related pathologies underlie the AD risk associated with PRSAPOE but not PRSnon‐APOE. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood‐derived DNA methylation as a promising tool for early dementia risk detection. METHODS: In conjunction with an extensive array of machine learning techniques, we employed whole blood genome‐wide DNA methylation data as a surrogate for 14 modifiable and non‐modifiable factors in the assessment of dementia risk in independent dementia cohorts. RESULTS: We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross‐sectionally, independent of age and sex (P = 2.0 × 10−3). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)‐Learning = 2.47) and Parkinson's disease (hazard ratio for MCI/dementia = 2.59). DISCUSSION: Our work shows the potential of employing blood‐derived DNA methylation data in the assessment of dementia risk. Highlights: We used whole blood DNA methylation as a surrogate for 14 dementia risk factors.Created a multivariate methylation risk score for predicting cognitive impairment.Emphasized the role of machine learning and omics data in predicting dementia.The score predicts cognitive impairment development at the population level. [ABSTRACT FROM AUTHOR]

Communication is an essential aspect of care for all patients but is especially important for individuals with Alzheimer’s disease or other forms of dementia. Nurses who care for persons living with dementia (PwD), as well as family members and caregivers, need understanding of verbal and nonverbal communication techniques and approaches that are effective throughout the stages of dementia. Spiritual assessment and care also are critical. This article provides evidence-based and biblical examples for communication as a healing art in caring for PwD. [ABSTRACT FROM AUTHOR]

A progressive neurodegenerative disorder that leads to cognitive decline and memory loss is known as Alzheimer's Disease (AD). Researchers propose an integrated framework centered on brain atrophy analysis and hippocampus segmentation to predict AD and its subtypes. This approach augments the accurate prediction of AD subtype classification, thus addressing the lack of emphasis in prevailing works. Primarily, the T1-weighted brain Magnetic Resonance Imaging (MRI) images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database undergo preprocessing. After that, for spatiotemporal evaluation, region segmentation, tau accumulation analysis, and Feature Extraction (FE), the image is processed. By employing the Fisher-Kolmogorov (FK) model, the essential parameters are extracted in spatio-temporal evaluation. In the meantime, for tissue segmentation, the Knowledge Partitioned Clustering (KPC) is utilized, and for hippocampus segmentation, the Kullback-Leibler Within-layer Regularized UNet (KLW-RU-Net) is employed. Moreover, by binarizing the image, the tau accumulation is analyzed; in addition, Principal Component Analysis (PCA) is utilized for FE. After PCA, the Adaptive Step-sized Gauss Rabbits Optimization (ASGRO) is employed for feature selection. Subsequently, to classify AD, the Dilated Derivative Sigmoid-Weighted DenseNet (DD-SWDN) is employed. Additionally, by employing Type-1 Fuzzy Logic (T1FL), the subtype of AD is classified, thus achieving higher accuracy for AD subtype classification. Therefore, as per these outcomes, the proposed work performs better than the other conventional approaches. [ABSTRACT FROM AUTHOR]

Background: Astrocytes have recently gained attention as key players in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease. Numerous differentiation protocols have been developed to study human astrocytes in vitro. However, the properties of the resulting glia are inconsistent, making it difficult to select an appropriate method for a given research question. Therefore, we compared three approaches for the generation of iPSC-derived astrocytes. We performed a detailed analysis using a widely used long serum-free (LSFP) and short serum-free (SSFP) protocol, as well as a TUSP protocol using serum for a limited time of differentiation. Results: We used RNA sequencing and immunochemistry to characterize the cultures. Astrocytes generated by the LSFP and SSFP methods differed significantly in their characteristics from those generated by the TUSP method using serum. The TUSP astrocytes had a less neuronal pattern, showed a higher degree of extracellular matrix formation, and were more mature. The short-term presence of FBS in the medium facilitated the induction of astroglia characteristics but did not result in reactive astrocytes. Data from cell-type deconvolution analysis applied to bulk transcriptomes from the cultures assessed their similarity to primary and fetal human astrocytes. Conclusions: Overall, our analyses highlight the need to consider the advantages and disadvantages of a given differentiation protocol for solving specific research tasks or drug discovery studies with iPSC-derived astrocytes. [ABSTRACT FROM AUTHOR]

The progressive form of Alzheimer's disease (AD) is a neurological condition marked by decline in older people's memory and cognition. Scopolamine is a behavioral technique that is frequently used to study cognitive disorders, such as Alzheimer's disease. This investigation aimed to determine the protective effects of ethanolic extracts derived from Sterculia guttata (ESG) on neurological & pathological changes induced by Scopolamine in rats with Alzheimer's. The ESG procured through a 48-hour hot maceration, followed by column chromatography, isolation and characterization using techniques such as FTIR, 1HNMR, 13CNMR and mass spectra. A flavonoid called Diosmin was identified in the extract. Rats were segregated into five groups: normal, scopolamine, scopolamine + Donepezil, scopolamine + ESG (200mg per kg orally), & scopolamine + ESG (400mg per kg orally) for a study of 14 day duration. Memory & learning abilities were assessed using the rectangular maze and Cook's pole climbing model. Additionally, biochemical parameters and brain histology were analyzed. ESG treatment mitigated scopolamine-induced changes in acetylcholinesterase, dopamine, serotonin, glutamate, and GABA levels, suggesting neuroprotection. These findings propose that ethanolic extracts of Sterculia guttata (ESG) show promise as effective preventive or therapeutic agents due to their potential for neuroprotection & cognitive enhancement in AD. [ABSTRACT FROM AUTHOR]

• We conducted a meta-analysis of twenty-two trials involving 1074 adults with mild cognitive impairment and Alzheimer's disease. • The effects of transcranial direct current stimulation (tDCS) on various on global cognitions were assessed. • The tDCS can ameliorate global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS. To systematically assess the effectiveness of transcranial direct current stimulation (tDCS) on global cognition in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Ten databases were retrieved for pertinent Chinese and English studies published up until February 2023. Two researchers independently selected the literature, extracted the data, evaluated using the Cochrane Collaboration's quality criteria, and then cross-checked. Meta-analysis was performed using RevMan 5.4. 22 studies involving 1074 patients were included. Compared with the control group received the interventions such as pharmacotherapy, cognitive stimulation, et al., with/without sham-tDCS, while the experiment group received tDCS added to the interventions of the control group. The meta-analysis found that tDCS increased MMSE, MoCA, MODA scores and reduced the P300 latency scores (all P < 0.05). The tDCS can ameliorate the global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS. [ABSTRACT FROM AUTHOR]

• The sense of self is diminished in AD. • Institutionalization can contribute to the diminished sense of self in AD. • Activities that are likely to enhance the sense self should be a priority in institutions. In this longitudinal study, we investigated the effects of institutionalization on the sense-of-self in individuals with Alzheimer's Disease (AD). We recruited two groups of participants: one living in care facilities (i.e., institutionalized-group) and another group living in their own home (i.e., non-institutionalized-group). In the two groups, we assessed the "Who-am-I" task on which participants were invited to provide statements beginning with the phrase "I am" that they felt were essential in defining who they are. We assessed this task, in the two groups, at a baseline (approximately one-month before-institutionalization) and at a follow-up (approximately six months after institutionalization). We analyzed whether responses on the "Who-am-I" task reflected physical-, social-, or psychological-self. Unlike at the baseline, fewer statements describing physical-, social-, and psychological-self were observed in the institutionalization than in the non-institutionalized group at the follow up. These findings demonstrate negative effects of institutionalization on the sense of self in AD. [ABSTRACT FROM AUTHOR]

• Acute exercise has a positive effect on enhancing cognitive function in elderly individuals with AD and MCI. • The effectiveness of acute exercise in preventing various types of dementia and AD shows a dose-response trend. • Acute exercise (aerobic or resistance) can temporarily increase the levels of some neuroprotective growth factors and enhance the neurocognitive abilities of elderly MCI patients. This narrative review follows the JBI approach and comprehensively explores the effects and mechanisms of acute exercise on cognitive function in Alzheimer's disease (AD) and Mild cognitive impairment (MCI) patients. The results showed that the combination of acute exercise and cognitive training improved the cognitive function of AD patients better than aerobic exercise or resistance training alone. For patients with MCI, moderate intensity acute aerobic exercise and resistance exercise were beneficial to enhance Inhibitory control (IC), but high-intensity acute exercise was adverse to improve IC; Brain-derived neurotrophic factor (BDNF) and Insulin-like growth factor 1 (IGF-1) may assume the potential mediating mechanism of acute exercise on cognitive function in AD and MCI patients, but more research is needed to further confirm this mechanism. [ABSTRACT FROM AUTHOR]

Importance: Alzheimer's disease (AD) is the most common cause of dementia in the elderly with the incidence rising exponentially after the age of 65 years. Unfortunately, effective treatments are extremely limited and definite diagnosis can only be made at autopsy. This is in part due to our limited understanding of the complex pathophysiology, including the various genetic, environmental, and metabolic contributing factors. In an effort to better understand this complex disease, researchers have employed nonhuman primates as translational models. Case Presentation: This report aims to describe the AD-like neuropathology in the brain of a 37-year-old female baboon (Papio hamadryas), which at the time of her death made her the oldest hamadryas baboon at any member institution of the Association of Zoos and Aquariums. A diagnostic necropsy was performed, and the brain was evaluated for neurodegenerative disease. Frequent amyloid-ß deposits were identified, consistent with what has been described in other geriatric nonhuman primates. Phospho-tau pathology, including neurofibrillary tangles, a feature not well-described in other primate models, was also abundant. Conclusions and Relevance: Our results suggest that more detailed, prospective, longitudinal studies are warranted utilizing this particular species to see if they represent a viable model for human brain aging. [ABSTRACT FROM AUTHOR]

Introduction: Living with dementia can be challenging, even more so for people diagnosed before age 65. Loss of identity is one of the main subjective consequences dementia poses at this stage in life due to the loss of social relations and daily activities. While a growing body of research is reporting the experienced impact of early-onset dementia on identity for this group, studies synthesizing this knowledge are very limited. Therefore, we have conducted a meta-ethnographic review to explain how people with early-onset dementia form their sense of identity. Method: A systematic review of literature from five databases was conducted. Ten original studies published between 2004 and 2020 were included and analyzed using an interpretive approach. Findings: A conceptual interpretation emerged from the analysis, showing that social arenas and activities of daily life, as well as assumptions about dementia and natural aging made by the participants and society, influenced the participants' sense of identity. Conclusion: Being in nonjudgmental environments can support people with early-onset dementia in creating continuity and positive connections in their personal history. Providing such environments can be a viable venue for healthcare professionals to support people with early-onset dementia in maintaining a positive sense of identity. [ABSTRACT FROM AUTHOR]

Against the backdrop of a desperate wait for treatment for Alzheimer's, patients and their care partners are actively seeking newly approved anti-amyloid antibody treatments. These drugs may reduce cognitive decline but also increase the risk of swelling, edema, and encephalitis. In this period of uncertainty, there is a need for interdisciplinary deliberation about treatment options. The radiology nurse, equipped with knowledge of individuals' care needs and ethical principles, is ideally positioned to encourage communication among different parties to ensure ethical care. • The risk/benefit ratio of new antibody treatments for Alzheimer's is still unknown. • Interdisciplinary debate can lead to ethical progress regarding the benefits of these treatments to patients. • The radiology nurse is ideally positioned to ensure ethical care. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is projected to affect a preponderant proportion of the aging population. Lifelong dietary habits have been hypothesized to play a role in preventing cognitive decline. Among the most studied dietary components, fish consumptionhas been extensively studied for its potential effects on the human brain. Aims: To perform a meta-analysis of observational studies exploring the association between fish intake and cognitive impairment/decline and all types of dementia. Methods: A systematic search of electronic databases was performed to identify observational studies providing quantitative data on fish consumption and outcomes of interest. Random effects models for meta-analyses using only extreme exposure categories, subgroup analyses, and dose-response analyses were performed to estimate cumulative risk ratios (RRs) and 95% confidence intervals (CIs). Results: The meta-analysis comprised 35 studies. Individuals reporting the highest vs. the lowest fish consumption were associated with a lower likelihood of cognitive impairment/decline (RR = 0.82, 95% CI: 0.75, 0.90, I2 = 61.1%), dementia (RR = 0.82, 95% CI: 0.73, 0.93, I2 = 38.7%), and Alzheimer's disease (RR = 0.80, 95% CI: 0.67, 0.96, I2 = 20.3%). The dose-response relation revealed a significantly decreased risk of cognitive impairment/decline and all cognitive outcomes across higher levels of fish intake up to 30% for 150 g/d (RR = 0.70, 95% CI: 0.52, 0.95). The results of this relation based on APOE ε4 allele status was mixed based on the outcome investigated. Conclusions: Current findings suggest fish consumption is associated with a lower risk of cognitive impairment/decline in a dose-response manner, while for dementia and Alzheimer's disease there is a need for further studies to improve the strength of evidence. [ABSTRACT FROM AUTHOR]

Background: Substantial evidence supports that glaucoma and dementia share pathological mechanisms and pathogenic risk factors. However, the association between glaucoma, cognitive decline and dementia has yet to be elucidated. Objective: This study was aimed to assess whether glaucoma increase the risk of dementia or cognitive impairment. Methods: PubMed, Cochrane Library, Web of Science, and EMBASE databases for cohort or case-control studies were searched from inception to March 10, 2024. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to the risk of bias. Heterogeneity was rigorously evaluated using the I2 test, while publication bias was assessed by visual inspection of the funnel plot and by Egger' s regression asymmetry test. Subgroup analyses were applied to determine the sources of heterogeneity. Results: Twenty-seven studies covering 9,061,675 individuals were included. Pooled analyses indicated that glaucoma increased the risk of all-cause dementia, Alzheimer's disease, vascular dementia, and cognitive impairment. Subgroup analysis showed that the prevalence of dementia was 2.90 (95% CI: 1.45–5.77) in age ≥ 65 years and 2.07 (95% CI: 1.18–3.62) in age<65 years; the incidence rates in female glaucoma patients was 1.46 (95% CI: 1.06-2.00), respectively, which was no statistical significance in male patients. Among glaucoma types, POAG was more likely to develop dementia and cognitive impairment. There were also differences in regional distribution, with the highest prevalence in the Asia region, while glaucoma was not associated with dementia in Europe and North America regions. Conclusion: Glaucoma increased the risk of subsequent cognitive impairment and dementia. The type of glaucoma, gender, age, and region composition of the study population may significantly affect the relationship between glaucoma and dementia. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders, notably Alzheimer's, pose an escalating global health challenge. Marked by the degeneration of brain neurons, these conditions lead to a gradual decline in nerve cells. Worldwide, over 55 million people grapple with dementia, with Alzheimer's prominently impacting the aging demographic. The primary hurdle to early Alzheimer's detection is the widespread lack of awareness. The main goal is to design and implement an artificial intelligence system using deep learning (DL) to detect Alzheimer's disease (AD) through medical images and classify them into various stages, such as non-demented, moderate dementia, mild dementia, and very mild dementia. The dataset contains 6400 magnetic resonance images in .jpg format, with standardized dimensions of 176 × 208 pixels. To demonstrate the advantages of data augmentation and transformation techniques, four scenarios were created: two without these techniques, utilizing the Adam and SGD optimizers, and two with these techniques, also employing the Adam and SGD optimizers, respectively. The main results revealed that scenarios utilizing these techniques exhibited more stable performance when validated with a new dataset. Scenario 3, using the Adam optimizer, achieved a weighted average accuracy of 91.83%, whereas scenario 4, employing the SGD optimizer, reached 87.58% accuracy. In contrast, scenarios 1 and 2, which omitted these techniques, obtained low accuracies below 55%. It is concluded that classifying AD with a DL model exceeding 90% accuracy is feasible. This is the importance of utilizing data augmentation and transformation techniques to improve generalizability to input image variations, which is a consistent factor in the healthcare sector. [ABSTRACT FROM AUTHOR]