Journal of Alzheimer's Disease最新文献

Background: The association between androgen deprivation therapy (ADT) and dementia risk is controversial, and the dose-response relationship between them remains unclear.

Objective: We aim to further clarify the relationship between ADT and dementia risk.

Methods: PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched up to September 2024 to identify relevant studies. A meta-analysis was conducted using hazard ratios (HR) and 95% confidence intervals (CI) as pooled indicators. The robust error meta-regression (REMR) approach was performed to explore the dose-response relationship. Heterogeneity was assessed using I² statistics, and subgroup analysis, sensitivity analysis, and meta-regressions were conducted. Publication bias was evaluated with a funnel plot and Egger's test.

Results: Our meta-analysis of 21 studies involving 2,278,835 patients revealed that ADT significantly increased the risk of overall dementia (HR = 1.14, 95% CI: 1.06-1.20) and Alzheimer's disease (AD) (HR = 1.15, 95% CI: 1.06-1.23), but not non-AD dementia (HR = 1.01, 95% CI: 0.89-1.16). For ADT subtypes, anti-androgens increased the risk of overall dementia (HR = 1.27, 95% CI: 1.09-1.49), particularly for AD (HR = 1.53, 95% CI: 1.19-1.97), while Luteinizing hormone-releasing hormone therapy and bilateral orchiectomy were not linked to the risk of any dementia subtype. A bell-shaped non-linear relationship between ADT duration and dementia risk was observed, with the highest risk observed at 15.5 to 21.5 months (HR = 1.25), which was confirmed by subgroup analysis for AD.

Conclusions: The risk of overall dementia and AD were found to be significantly associated with ADT in a bell-shaped dose-response effect.

Background: The relationship between peripheral cytokines and neuroimaging biomarkers for Alzheimer's disease (AD) is not yet well established.

Objective: To determine the association of cytokine plasma levels with brain amyloid deposition, cortical glucose metabolism, hippocampal volume, and white matter lesions (WMLs) in older adults with mild cognitive impairment (MCI).

Methods: We recruited 50 older individuals with amnestic MCI (25 men and 25 women; median age, 75 years) and performed plasma analysis, ¹¹C-Pittsburgh compound-B positron-emission tomography (PiB-PET), ¹⁸F-fluorodeoxyglucose positron-emission tomography, and magnetic resonance imaging. Global PiB and fluorodeoxyglucose (FDG) uptake were assessed by the ratio of the voxel number-weighted average of the mean uptake in the frontal, temporoparietal, and posterior cingulate, in reference to the cerebellum. The Fazekas scale was used to evaluate WMLs. Plasma levels of 48 cytokines were simultaneously measured with bead-based multiplex assays.

Results: The plasma levels of IL-2Ra, IL-3, IL-5, IL-7, IL-9, IL-16, IL-18, fibroblast growth factor (FGF-basic), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein-1α (MIP-1α), regulated on activation, normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), cutaneous T-cell attracting chemokine (CTACK), growth-regulated oncogene α (GROα), hepatocyte growth factor (HGF), interferon-α2 (IFN-α2), leukemia inhibitory factor (LIF), monocyte chemoattractant protein-3 (MCP-3), β-nerve growth factor (β-NGF), stem cell factor (SCF), stem cell growth factor-β (SCGF-β), and TNF-related apoptosis-inducing ligand (TRAIL) were significantly associated with global PiB uptake, whereas those of IL-7 and GROα were significantly associated with hippocampal volume after covariate adjustment and false discovery rate correction.

Conclusions: Plasma cytokines are associated with brain amyloid deposition rather than brain dysfunction or hippocampal atrophy. Moreover, cytokines may play important roles in early-stage AD pathophysiology.

Background: A disintegrin and metalloproteinase 17 (ADAM-17) has multiple pathophysiological functions in Alzheimer's disease (AD). However, the clinical relevance of ADAM-17 in AD is not clear yet.

Objective: This study aims to investigate the levels of circulating ADAM-17 and their association with AD.

Methods: This cross-sectional study recruited 40 normal cognition (NC) participants and 36 AD patients. Plasma ADAM-17 and biomarkers of neurodegeneration were determined. The association of plasma ADAM-17 with cognitive functions and biomarkers of neurodegeneration was analyzed.

Results: Plasma ADAM-17 levels were elevated in AD patients in comparison with NC subjects. Plasma ADAM-17 was positively associated with Clinical Dementia Rating (CDR) scores, but negatively associated with the Mini-Mental State Examination scores and Montreal Cognitive Assessment scores. Plasma ADAM-17 levels were positively associated with the levels of Aβ₄₀, Aβ₄₂, and p-Tau181.

Conclusions: These findings suggest a link between ADAM-17 and the pathogenesis of AD from a clinical perspective.

Background: Recent technological advances in digital assessment of auditory and cognitive function may be used to circumvent the costs associated to screening for cognitive decline in the general population. Pre-clinical cognitive screening could have a transformative impact for preventive care in our increasingly old world population. However, advances in digital assessment need to be adapted for Spanish-speaking populations as innovation occurs mainly in English.

Objective: This study explores the potential of a novel screening battery for cognitive decline that utilizes digital tests of cognitive and auditory function adapted to the Spanish language.

Methods: Participants were evaluated on standard clinical scales and questionnaires, and on a digital battery of auditory and cognitive tests with potential clinical value to screen cognitive decline.

Results: We report the ability to detect minimal cognitive impairment (MCI; 3/10 tests) and dementia (10/10 tests) of each digital test and the full battery. We further show concurrent validity for cognitive screening with the Montreal Cognitive Assessment (MoCA) and describe the shared variance across tests in the battery. Lastly, we show multiple regression models predicted with medium sensitivity (57%) and high specificity (97%) the dementia cases, and with high sensitivity (93%) but low specificity (31%) the MCI cases.

Conclusions: Overall, this study demonstrates discriminatory value and concurrent validity to screen for cognitive decline in older adults using open-access digital auditory and cognitive tests in the Spanish language. Follow-up studies with larger and more diverse samples will be instrumental in achieving cognitive screening procedures for the general population.

Background: Synaptic transmission dysfunction is associated with a range of neurological disorders, including Alzheimer's disease (AD). However, the role of γ-aminobutyric acid (GABA)-mediated synaptic inhibition in AD has not been fully explored.

Objective: We studied basal, GABA-activated slow spontaneous synaptic currents (sIPSCs) in dentate gyrus (DG) granule cells in the dorsal hippocampus of an AD mouse model (tg-APPSwe) and investigated insulin's modulatory effects.

Methods: GABA-activated slow sIPSCs were recorded in the DG granule cells by whole-cell patch--clamp recordings in dorsal hippocampal brain slices from 5-6 (adult) and 10-12 (aged) months old wild-type (WT) and AD mice, in the presence or absence of insulin (1 nM).

Results: The median 10-90% rise time of slow sIPSCs significantly decreased with age (10-12 months vs. 5-6 months) only in AD mice. The median amplitude of the slow sIPSCs was decreased in adult and aged AD mice as compared to WT mice whereas the slow sIPSCs frequency was only reduced in the aged WT mice. The median 63% decay time and total current density of the slow IPSCs was significantly decreased in the aged AD mice as compared to both WT mice and to the adult AD mice. Insulin application exerted no effect on slow sIPSCs properties in any of the animal groups.

Conclusions: The characteristics of the slow sIPSCs recorded in DG granule cells of dorsal hippocampus from WT and AD mice are altered by age- and disease-state, whereas insulin has negligible effects.

Digital health innovations hold diagnostic and therapeutic promise but may be subject to biases for underrepresented groups. We explored perceptions of using artificial intelligence (AI) diagnostics for dementia through a focus group as part of the Automated Brain Image Analysis for Timely and Equitable Dementia Diagnosis (ABATED) study. Qualitative feedback from a diverse public engagement group indicated that cultural variations in trust and acceptability of AI diagnostics may be an unrecognised source of real-world inequity. Efforts focused on the adoption of AI diagnostics in memory clinic pathways should aim to recognise and account for this issue.

Background: Nutrition risk is common in Alzheimer's disease and is associated with symptoms of dementia, cognitive decline, institutionalization, and mortality. Family caregivers who increasingly manage nutrition needs of persons with dementia (PWD) experience high caregiver burden, low health literacy, and nutrition risk. Few interventions for informal caregivers have included nutrition.

Objective: To inform design of a future caregiver nutrition intervention.

Methods: This cross-sectional study used a convergent mixed methods approach to 1) assess nutrition status among PWD and caregiver dyads (measures in common included Mini Nutrition Assessment, skin carotenoid, and handgrip strength), and 2) interview caregivers to identify needs and barriers for nutrition intervention. We hypothesized caregiver nutrition literacy is associated with PWD nutrition risk. Data collected in nutrition assessment and interviews were analyzed separately then side-by-side for comparison.

Results: Of 50 dyads, 48% had at least one individual exhibiting nutrition risk, and nutrition status categories (χ²= 6.25, p = 0.012) between caregivers and PWD were related. Caregiver nutrition literacy was associated with 1) PWD factors including nutrition risk (rho = 0.244), body mass index (BMI) (rho = 0.421), handgrip strength (rho = 0.283), and skin carotenoid (rho = 0.351), and 2) Caregiver factors including nutrition risk (rho = 0.304), diet quality (rho = 0.304), and BMI (rho = 0.333). Interviews with 18 caregivers found caregivers prioritize PWD nutrition, provide more PWD nutrition care since diagnosis, experience social isolation, and would attend nutrition interventions if PWD are included.

Conclusions: Nutrition risk was more common among caregivers when PWD demonstrated nutrition risk. Factors present in individuals within the dyad were associated with partner nutrition risk. Future research should identify effective approaches for intervening on dyadic nutrition risk.

Background: Hippocampal atrophy is linked to memory and cognitive deficits, preceding clinical diagnosis of mild cognitive impairment (MCI) by decades. Morphometry changes in the hippocampal formation (HF) and their relationship to tau deposition in non-demented individuals remains unclear.

Objective: To investigate morphometry changes in the HF and their association with tau deposition in a non-demented cohort.

Methods: Eighty-three subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent T1-weighted MRI and Tau-PET scans at baseline and longitudinal follow-up. Participants were divided into amyloid-negative (Aβ-) and amyloid-positive (Aβ+) groups. Hippocampal volume/thickness were measured, and associations with tau deposition in temporal regions were examined using multivariable linear regression.

Results: No significant association was found between the hippocampal volume/thickness and tau deposition of temporal regions for the Aβ- group. For the Aβ+ group, the hippocampal thickness was significantly associated with tau deposition of entorhinal cortex (ERC) for both hemispheres, and temporal pole, inferior temporal, and middle temporal regions for right hippocampi with the longitudinal follow up scans, while no significant association with the baseline scans. It was interesting that there was strong association between the baseline tau deposition of ERC and temporal pole and the longitudinal follow up thickness of left hippocampi, while the associated regions for the right hemisphere were ERC, temporal pole, and inferior temporal regions.

Conclusions: Hippocampal atrophy may precede cognitive symptoms, with tau deposition in adjacent temporal regions contributing to hippocampal changes. The right HF appears more vulnerable than the left, indicating hemispheric differences in pathology.

Background: Alzheimer's disease is the most common age-related dementia. Recent compelling evidence from previous retrospective electronic health record (EHRs) studies suggests that herpes simplex virus (HSV) infections may be a risk factor for developing dementia. However, no age and propensity score matched studies have been published in a United States general population cohort study to date.

Objective: We aimed to identify whether HSV infection shows a significantly increased risk of the development of dementia in a sizable and heterogeneous cohort. We investigated whether herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), or coinfections with both serotypes pose a greater risk of developing dementia across different biological sexes and racial groups.

Methods: EHRs from patients with a history of HSV or specific serotypes (HSV1 or HSV2) infection were selected for analysis. These records were compared to a propensity-matched control group and analyzed for hazard and odds ratios through TriNetX.

Results: There was a significant difference in dementia incidence in the HSV-infected group versus the control. Individuals with a history of HSV, HSV1, HSV2, and coinfection all showed a significant risk of developing dementia compared to controls. Males with HSV2 are at a higher risk of dementia outcome than females with HSV2.

Conclusions: While consistent with previous reports, these findings are the first to establish a higher risk of developing dementia in patients who have any HSV diagnosis using a nationwide, population-based matched cohort study in the United States.