Journal of Alzheimer's disease reports最新文献

Background: Chronic microglial activation is a key characteristic of Alzheimer's disease (AD). In mouse models of AD, microglial activation is considered associated with microglial cell population expansion.

Objective: To elucidate species- and gene-dosage-dependent differences and similarities in microglial cell population expansion in response to amyloid-β (Aβ) plaque pathology.

Methods: The total number of Iba1⁺ microglia in the neocortex of hemizygous APP_swe/PS1_ΔE9 (APP/PS1) mice and hemi- and homozygous TgF344-AD rats, carrying the same human mutations, was estimated by use of stereological techniques. Furthermore, microglial cluster formation was assessed. Proliferation was assessed in the mouse model.

Results: A significant two-fold increase in microglia was observed in the neocortex of hemizygous APP/PS1 mice at 18 months and of homozygous TgF344-AD rats at 17 months. In comparison, the number of microglia in hemizygous TgF344-AD rats, remained constant from 4 to 17 months. Microglial clusters formed prior to the increase in microglial numbers in both species. The clusters were typically small, surrounding the smaller-sized Aβ plaques, occasionally also containing recently proliferated microglia. The Aβ plaque loads were comparable in hemizygous TgF344-AD rats and APP/PS1 mice, and two-three-fold higher in homozygous TgF344-AD rats. The microglial population remained constant across ages in wild types in both species.

Conclusions: Transgenic mouse and rat AD models show significant differences in microglial population expansion, with a more restrained expansion in the rat. However, in both species and regardless of gene-dosage, population expansion is preceded by microglial clustering around Aβ plaques, indicating that cluster-formation is a key event in AD neuropathology.

Background: Sensory stimulation, such as sight, hearing, and smell influence healthy neurological processing evident by the growing literature which demonstrates that sensory loss increases Alzheimer's disease and related dementias (ADRD) risk. While these associations are critical in advancing the field, less is known related to cortical-level sensory processing and ADRD as a primary mechanism in functional performance and behavioral regulation. However, it is unclear how sensory processing assessment is used in clinical practice related to intervention.

Objective: This systematic review explores the current state of evidence of sensory processing assessment before sensory-based interventions in ADRD care.

Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 update to exhaustively examine published literature (1999-2024) regarding sensory processing assessment in ADRD prior to sensory-based intervention delivery.

Results: The systematic search identified 14,928 articles, all of which were screened for inclusion. No studies specifically assessed sensory processing prior to providing sensory-based interventions in older adults with ADRD.

Conclusions: Findings of this systematic review illustrate a substantial gap in the field of ADRD care as sensory interventions are used in clinical care, yet there is insufficient evidence of sensory processing assessment to appropriately guide safe use for individuals with ADRD.

Background: Instrumental Activities of Daily Living (IADL) are key indicators of functional decline in dementia, but culturally adapted tools for Latin America are scarce.

Objective: This study aims to assess the validity and robustness of a new Peruvian version of the Amsterdam Instrumental Activities of Daily Living Questionnaire-Short Version (A-IADL-Q-SV-P).

Methods: We recruited 171 participants from a cognitive clinic in Peru (81 Clinical Dementia Rating (CDR) = 0, 70 CDR = 1, 20 CDR = 2), including 54 with Alzheimer's disease and 36 with frontotemporal dementia. Validity of the A-IADL-Q-SV-P was assessed using quadratic discriminant analysis to classify CDR level. Spearman correlations tested robustness with demographics (age, sex, education) and associations with cognitive (Mini-Mental State Examination), mood (Generalized Anxiety Disorder-7, Geriatric Depression Scale, and Neuropsychiatric Inventory), and functionality (Pfeffer Functional Activities Questionnaire and Technology-Activities of Daily Living Questionnaire) measures.

Results: The A-IADL-Q-SV-P achieved excellent accuracy for classifying dementia severity (accuracy: 0.853, AUC > 0.92). The ability to classify normal cognition had a sensitivity of 0.95 and a specificity of 0.91, and results were similar for patients with Alzheimer's disease or frontotemporal dementia (accuracy > 0.88, sensitivity > 0.95, and specificity > 0.88, AUC > 0.91). We also found weak associations with age, sex, and education (|rho| < 0.2). Furthermore, the A-IADL-Q-SV-P had strong associations with other clinical scales (|rho| > 0.4), particularly in relation to cognition (rho = -0.70) and functionality (rho > 0.87).

Conclusions: A-IADL-Q-SV-P demonstrated excellent accuracy in classifying dementia severity, with strong correlations to cognitive and other functionality measures. This supports the utility of A-IADL-Q-SV-P as a culturally adapted tool for assessing functional decline in dementia.

Background: Alzheimer's disease (AD) is a leading cause of dementia with societal and economic burdens. While recent therapies offer disease-modifying potential, concerns remain about efficacy and safety. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), used in type 2 diabetes, show neuroprotective effects via reduced neuroinflammation and amyloid burden.

Objective: To evaluate whether GLP-1RA use is associated with a reduced risk of incident dementia in adults aged ≥50 years using real-world data.

Methods: We conducted a retrospective cohort study using the TriNetX platform, analyzing records from 142 healthcare organizations. Adults aged ≥50 were included, comparing GLP-1RA users (liraglutide, semaglutide, dulaglutide, exenatide, albiglutide) to non-users. Propensity-score matching balanced demographics and comorbidities. Incident dementia, defined by ICD-10 codes, was analyzed with Cox proportional-hazards models.

Results: Matched cohorts (n = 147,505 each) had similar baseline characteristics. Dementia incidence was lower in GLP-1RA users (0.20% versus 0.44%), with a hazard ratio of 0.30 (95% CI 0.28-0.33; p < 0.001).

Conclusions: GLP-1RA use was associated with a 70% reduced dementia risk, warranting further clinical evaluation.

Background: Timely diagnosis of Alzheimer's disease (AD) remains challenging in the United Kingdom and improvements are needed with the introduction of new therapies.

Objective: To examine the United Kingdom diagnostic and current treatment journey for people with mild cognitive impairment (MCI) and AD dementia to identify future opportunities for new treatments.

Methods: Physician-reported data were drawn from the Adelphi Real World Dementia Disease Specific Programme™, a cross-sectional survey of physicians treating patients with MCI or AD dementia in the United Kingdom between 2022 and 2024. Analyses were descriptive.

Results: Physicians (n = 109) reported data for 717 patients with MCI or AD dementia (including 264 with MCI or mild dementia). Overall median (interquartile range) time from symptom onset to first consultation was 26.0 (9.1-52.9) weeks. Time from consultation to diagnosis, for patients not diagnosed at initial consultation, was 15.2 (5.1-21.0) weeks for patients who first consulted and were diagnosed by a general practitioner and 21.9 (12.6-39.0) weeks for those who consulted a general practitioner and were diagnosed by a specialist. Few patients (4.9%) had a biomarker-confirmed diagnosis. Delays due to waiting for specialist referrals and diagnostic tests were reported for 57.6% and 26.9% of patients, respectively. Acetylcholinesterase inhibitors were the most common first-line treatment (82.0%).

Conclusions: Our data highlighted delays in AD diagnosis and potential areas for United Kingdom health system improvement. Expediting timely diagnosis through increased public awareness, expanded biomarker use and addressing disparities in services is crucial to maximize access to emerging new therapies.

Alzheimer's disease and related dementias (ADRD) are complex and rapidly growing public health challenges that require integrative, collaborative approaches. To meet this need, the Alzheimer's Disease Research Center (ADRC) of South Carolina, a state-funded partnership across multiple institutions, has embraced a team science model that brings together expertise from four key disciplines: neuroimaging-neurology, health sciences, molecular biology, and engineering. This paper highlights the work at the University of South Carolina (USC) and how each discipline contributes uniquely yet collaboratively within a recurring loop model framework. Extending from USC's Cancer Prevention and Control Program, the framework guides scientific growth through four iterative phases: discovery, development, delivery, and dissemination. From identifying cellular and molecular biomarkers to applying neuroimaging for early diagnosis, utilizing wearable technologies for real-time monitoring, and analyzing statewide data to understand caregiver burden and health inequities, each group contributes to a comprehensive and translational research cycle. By supporting structured mentorship, cross-disciplinary pilot projects, and shared infrastructure, the ADRC initiatives advance research that is both scientifically rigorous and equity-focused. This approach provides a valuable framework for advancing ADRD research and can inform other institutions aiming to tackle similarly complex health issues from discovery through dissemination.

Posterior cortical atrophy (PCA) is a challenging diagnosis and is often misdiagnosed due to its subtle and atypical presentation. We present a woman with early-onset visuospatial dysfunction, apraxia, and dysgraphia. Neuroimaging revealed posterior atrophy with sparing of the hippocampi. Clinical features, neuropsychological findings, and neuroimaging were consistent with a diagnosis of PCA. The diagnosis was established based on the three-level PCA classification framework. This case highlights the importance of clinical evaluation and multidisciplinary collaboration in identifying atypical presentations of neurodegenerative diseases.

Background: The global burden of disease research shows that the disease burden of dementia (including Alzheimer's disease and other dementias) is increasing.

Objective: This study aims to analyze the trends of dementia deaths among residents in Suzhou and explore the impact of population aging on dementia mortality rates during the period from 2004 to 2023.

Methods: The study utilizes demographic dementia mortality data of Suzhou's registered residents over the 20-year period for comprehensive analysis. Joinpoint regression analysis was employed to estimate the average annual percentage changes (AAPC) in indicators for dementia. Using the method of decomposing the differences of mortality rates to evaluate the contribution of population aging to dementia mortality.

Results: The population composition ratios of aged ≥60 and ≥65 in 2023 were 25.70% and 20.24%, respectively; The number of dementia deaths from 2004 to 2023 was 24 014, and the average age of death caused by dementia increased from 79.74 ± 11.20 years old to 84.13 ± 8.49 years old. Dementia death age rose significantly over time, varying by gender. The crude mortality rate increased from 14.67/100 000 in 2004 to 21.55/100 000 in 2023, but the standardized mortality rate decreased from 9.16/100 000 in 2004 to 5.91/100 000 in 2023; The increase in the crude mortality rate of residents in 2023 was 213.66% attributed to the contribution rate of population aging.

Conclusions: The overall crude mortality rate of dementia among residents in Suzhou is still on the rise, and population aging is a key factor.

Background: Alzheimer's disease (AD) is a neurodegenerative disease, with APOE ε4 as the most common genetic risk factor. This protein has been implicated in amyloid-β peptide (Aβ)-mediated pathological processes in patients with AD. However, the mechanism by which APOE ε4 regulates cerebrospinal fluid (CSF) protein levels and Aβ₄₂ concentration in CSF during the pathogenesis of AD has not been clarified.

Objective: To determine whether APOE ε4 contributes to the pathogenesis of AD by altering Aβ₄₂ concentrations and protein levels in CSF.

Methods: A total of 228 AD patients were enrolled and assigned into the APOE non-ε4 carrier group (146 patients) and the APOE ε4 carrier group (82 patients). The concentration of Aβ₄₂ and protein levels in CSF, as well as APOE genotypes were quantified. Subsequently, the association of APOE ε4 with CSF biomarkers was explored through multiple logistic regression analysis.

Results: In APOE ε4 carriers, CSF Aβ₄₂ (p = 0.016) and the protein (p = 0.040) levels in CSF were lower compared with levels in the non-carrier group. Moreover, APOE ε4 carriage was associated with lower levels of CSF Aβ₄₂ (odds ratio 0.998, 95% confidence interval 0.995-1.000, p = 0.048) and CSF protein (odds ratio 0.004, 95% confidence interval 0.000-0.224, p = 0.007) in APOE ε4 carriers.

Conclusions: APOE ε4 modulates the CSF protein levels and CSF Aβ₄₂ concentrations in AD patients. This indicates that the APOE ε4 genotype and CSF protein levels may help monitor the progression of AD.

Background: Alzheimer's disease (AD) is the most common cause of dementia, characterized by a progressive deterioration of cognitive capacity and the ability to carry out activities of daily living (ADL). Hand motor function may also be impaired, with slower and less automated movements during fine motor tasks. The severity of impairments may depend on task characteristics and the age of onset of AD.

Objective: This study investigated hand motor function of persons with dementia due to AD during handwriting and sequential hand movements, focusing on the impact of task complexity and age at onset.

Methods: Kinematic analysis of handwriting and sequential hand movements was carried out in 24 AD patients (early-onset AD (EOAD): n = 13; late-onset AD (LOAD): n = 11) and 23 controls (≤ 65 years: n = 12; > 65 years: n = 11). To estimate the impact on patients' ADL performance, the Jebsen-Taylor Hand Function Test (JTHFT) was administered.

Results: AD patients exhibited a significantly lower handwriting and sequencing performance compared to healthy controls. Complexity effects were detectable for handwriting and sequencing; for z-standardized sequencing frequency, they were more prominent in AD patients than controls. Age at onset had no effect on handwriting or sequential hand movements; however, handwriting and sequencing frequency were predictive of JTHFT performance in EOAD, but not in LOAD.

Conclusions: Kinematic measures of both handwriting and sequential hand movements were able to capture impairments in AD patients. Deteriorations of frequencies seem to translate into deficits in simulated ADL performance only in EOAD.