Journal of Alzheimer's Disease最新文献

Background: Dementia is recognized as one of the prevalent neurocognitive disorders among older adults in Saudi Arabia, yet research efforts on its prevalence remains limited and fragmented, making it difficult to gain a full understanding of its epidemiology.

Objective: To explore dementia epidemiology and associated data within the older population in the sector of National Guard Health System (NGHS), Saudi Arabia.

Methods: This was a multicenter study that utilized medical records from NGHS centers across the country. We included data from all individuals aged 50 years and older who sought medical care between January 1, 2015, and January 1, 2023.

Results: Nearly half of the study's participants were men (51.9%), with the majority being diagnosed between the ages of 70-79 years (38.5%) and 80-89 years (31%). Dementia was identified in 3.37% of participants. The most prevalent subtype was late-onset Alzheimer's disease (35.6%), followed by unspecified dementia (18.4%). Significant differences between genders were observed, particularly in the age at diagnosis (p = 0.003) and the prevalence of ischemic strokes as a risk factor (p < 0.001).

Conclusions: In this multicenter study utilizing the NGHS cohort, Alzheimer's disease emerged as the most prevalent subtype of dementia. This research has the potential to influence clinical practices by enhancing the early identification and management of dementia and provides a solid foundation for developing evidence-based policy strategies to tackle the increasing challenges of dementia in Saudi Arabia.

Background: Cortico-basal degeneration (CBD) is a neurodegenerative disease typically responsible for cortico-basal syndrome (CBS) or progressive limb apraxia. Half of CBD patients, however, present atypical symptoms, making the diagnosis difficult.

Objective: We reported the case of a woman in her late sixties (BM208), an unusual case of autopsy-proven CBD, showing early signs of Benson's syndrome or posterior cortical atrophy. In addition, we compared cognitive performance and atrophy in different brain regions of BM208 with other neurodegenerative diseases patients to highlight clinical signs that could have guided the diagnosis earlier.

Methods: We retrospectively compared BM208 to patients with typical amnestic Alzheimer's disease (AD) (n = 18, Mini-Mental State Exam (MMSE) scores between 18 and 24), Benson's syndrome due to AD (n = 3), CBS/progressive supranuclear palsy (PSP) syndrome (n = 5), and Lewy body dementia (LBD) patients (n = 3) and a control group (n = 24). All these participants underwent an MMSE, a complete neuropsychological examination and 3DT1 MRI.

Results: Although BM208 was more severely cognitively impaired overall, her cognitive performance was more similar to Benson's syndrome patients' cognitive profile compared to CBS patients or any other degenerative pathology (typical AD/LBD). Consistently, although BM208 was more atrophic than all other groups, she showed cortical atrophy that matched a Benson's syndrome pattern more than typical AD or CBS. However, the analysis of subcortical atrophy revealed atrophy of the basal ganglia corresponding CBS cases. Furthermore, visual analyses on sagittal T1 images showed atrophy of the midbrain, characteristic of CBS/PSP syndrome.

Conclusions: These results highlight the additive value of fine-grained MRI subcortical quantification to diagnose non-AD rare neurodegenerative disorders.

Background: Alzheimer's disease (AD) and its monoclonal antibody therapies are associated with brain vasculitis and amyloid-related imaging abnormalities. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFAs), such as 11,12-epoxyeicosatetraenoic acid (EEQ), are anti-inflammatory and pro-resolution mediators, which are increased by dietary supplementation with ω-3 PUFAs. EpFAs are, however, enzymatically hydrolyzed by soluble epoxide hydrolase (sEH) in AD patients' macrophages in vivo and in vitro.

Objective: To repair amyloid-β 1-42 (Aβ) degradation by AD macrophages using the inhibitors of a) soluble epoxide hydrolase (sEHIs), termed TPPU and EC5026, together with EpFAs, or b) STING pathway termed H-151.

Methods: Immunobiology, immunochemistry, RNA sequencing, and confocal microscopy were used.

Results: In AD brain (examined postmortem), monocyte/macrophages upload Aβ in plaques and transfer it without degradation into brain microvessels, suffer apoptotis, and release Aβ, inducing vasculitis. The EpFAs of epoxyeicosatetraenoic acid (EEQ), along with the inhibitors TPPU and H-151, decrease inflammatory cytokines and regulate macrophage unfolded protein response to endoplasmic reticulum stress. Treatment of AD macrophages by TPPU with EEQ or by STING inhibitor H-151 increased uploading of Aβ after 2 hours and increased degradation of Aβ after 24 hours.

Conclusions: The sEHI inhibitor EC5026 and the STING inhibitor H-151 increased macrophage uptake and degradation of Aβ. EC5026 administration was safe in normal volunteers. EC5026 together with ω-3 PUFA supplementation are indicated for in a clinical trial in patients with mild cognitive impairment.

We assessed the severity of amyloid-β accumulation and white matter lesions (WML) in the brain, and their association with cognitive decline, in patients (n = 47) with Alzheimer's disease (AD). The mean cortical standardized uptake value ratio (mcSUVR) was derived from amyloid positron emission tomography, while the percentage of WML area relative to brain parenchymal area was determined using magnetic resonance imaging. Cognitive decline was positively correlated with WML severity (r = 0.50, p = 0.042) but not mcSUVR (Aβ accumulation). Managing vascular risk factors can prevent cognitive decline in patients with AD.

During decades scientists tried to unveil the genetic architecture of Alzheimer's disease (AD), recurring to increasingly larger sample numbers for genome-wide association studies (GWAS) in hope for higher statistical gains. Here, a retrospective look on the most prominent GWAS was performed, focusing on the quality of the diagnosis associated with the used data and databases. Different methods for AD diagnosis (or absence) carry different levels of accuracy and certainty applied to both subsets of cases and controls. Furthermore, the different phenotypes included in these databases were explored, as several incorporate other ageing comorbidities and might be encompassing many confounding agents as well. Age of the samples' donors and origin populations were also investigated as these could be biasing factors in posterior analyses. A tendency for looser diagnostic methods in more recent GWAS was observed, where greater datasets of individuals are analyzed, which may have been hampering the discovery of associated genetic variants. Specifically for AD, a diagnostic method conveying a clinical outcome may be distinct from the disease neuropathological assessment, since the first has a practical perspective that not necessarily needs a confirmation. Due to its properties and complex diagnosis, this work highlights the importance of the neuropathological confirmation of AD (or its absence) in the subjects considered for research purposes to avoid reaching statistically weak and/or misleading conclusions that may trigger further studies with powerless groundwork.

Background: The frequent presentation of Alzheimer's disease (AD) with neuropsychiatric symptoms (NPS) in the context of normal or minimally-impaired cognitive function led to the concept of Mild Behavioral Impairment (MBI). While MBI's impact on subsequent cognitive decline is recognized, its association with brain network changes in biologically-defined AD remains unexplored.

Objective: To investigate the correlation of structural covariance networks with MBI-C checklist sub-scores in biologically-defined AD patients.

Methods: We analyzed 33 biologically-defined AD patients, ranging from mild cognitive impairment to early dementia, all characterized as amyloid-positive through cerebrospinal fluid analysis or amyloid positron emission tomography scans. Regional network properties were assessed through graph theory.

Results: Affective dysregulation correlated with decreased segregation and integration in the right inferior frontal gyrus (IFG). Impulse dyscontrol and social inappropriateness correlated positively with centrality and efficiency in the right posterior cingulate cortex (PCC). Global network properties showed a preserved small-world organization.

Conclusions: This study reveals associations between MBI subdomains and structural brain network alterations in biologically-confirmed AD. The IFG's involvement is crucial for mood dysregulation, while the PCC could be involved in compensatory mechanisms for social cognition and impulse control. These findings underscore the significance of biomarker-based neuroimaging for the characterization of NPS across the AD spectrum.

Background: The head turning sign (HTS) consists in the patient turning his/her head towards the accompanying person in search for support when being asked questions. Although the HTS is known to be associated with cognitive impairment, previous investigations were biased towards Alzheimer's disease (AD) or did not differentiate between diverse dementia etiologies; moreover, little is known about the specific cognitive correlates of the HTS.

Objective: To assess the prevalence and clinical correlates of the HTS in patients with mild cognitive impairment (MCI) and dementia of various etiologies.

Methods: The HTS was recorded during the Mini-Mental State Examination (MMSE) in 232 MCI/dementia patients with the following etiological classification: AD (N = 121); frontotemporal lobar degeneration (FTLD; N = 24); Lewy body disease (LBD; N = 11); vascular (N = 29); mixed (N = 47).

Results: The overall prevalence of the HTS in the whole cohort was 27.6%. Albeit being descriptively higher in dementia (29.9%) versus MCI (22.7%), as well as descriptively lower in FTLD and LBD than in remaining subgroups, no significant association was detected between the HTS and either MCI/dementia status or etiology. HTS + patients were older and more frequently females, also reporting lower MMSE scores and differing from HTS- ones on Temporal and Spatial Orientation and Constructional Praxis sub-scores. An association between the HTS and lower MMSE scores was found in patients with MCI but not in those with dementia.

Conclusions: In patients with cognitive impairment due to diverse causes, the HTS might occur regardless of MCI versus dementia status and across different etiologies. MCI patients displaying the HTS might have more severe cognitive deficits.

Background: A novel neuroimaging signature of regional cortical thickness on brain MRI recently showed high potential for Alzheimer's disease and related dementias (ADRD) risk stratification in the community. How these findings translate to other populations, remains undetermined.

Objective: We aimed to replicate this novel ADRD neuroimaging marker in the population-based Rotterdam Study.

Methods: We included all participants from the population-based Rotterdam Study with brain-MRI between 2005-2016, and derived the signature using FreeSurfer. We computed hazard ratios and C-statistics for 10-year dementia risk, and betas for cross-sectional associations with cognition, comparing the novel signature to hippocampal volume, mean cortical thickness, and another cortical thickness signature (Dickerson's).

Results: Of 3249 participants (mean age 71.3 ± 8.0 years), 294 developed dementia (74.8% clinical AD) during a mean follow-up of 8.1 years. The novel ADRD signature had similar magnitude of associations as Dickerson's signature and cortical thickness for AD dementia (HR per 1-SD increase 0.87;0.78-0.96), but performed worse than all markers for all-cause dementia. Of the four neuroimaging markers, hippocampal volume showed the strongest associations with both risk of all-cause dementia and clinical AD dementia. The ADRD had the weakest association with general cognitive function (β per 1-SD increase 0.04;0.02-0.06), and executive function (β per 1-SD increase 0.02;0.00-0.04), followed by cortical thickness and Dickerson's, and hippocampal volume showed the strongest associations.

Conclusions: In this community-based study, the novel cortical thickness signature did not outperform hippocampal volume for dementia risk stratification. The importance of replication studies underlines the value of the current study. Replicating research findings is essential to establish robust biomarkers for dementia risk prediction.

Background: The adoption of Alzheimer's disease (AD) biomarkers in clinical practice is expected to increase following recent approval of disease-modifying therapies. Fully automated immunoassays, Elecsys platform, offer convenience and enhanced reliability.

Objective: This study was performed to evaluate the performance of the Elecsys assay in a Korean clinical setting, comparing its effectiveness to ELISA for detecting amyloid-PET positivity.

Methods: Cerebrospinal fluid (CSF) Aβ₄₂, pTau₁₈₁, tTau, pTau₁₈₁/Aβ₄₂, and tTau/Aβ₄₂ were evaluated using Elecsys kits on a Cobas e 411 analyzer and manual Innotest ELISA with paired frozen samples (n = 118) from subjects with cognitive status ranging from unimpaired to mild cognitive impairment and dementia.

Results: Strong linear correlations were observed between Elecsys- and ELISA-measured Aβ₄₂, pTau₁₈₁, and tTau levels. Receiver operating characteristic-based cutoff points for pTau₁₈₁/Aβ₄₂ (0.0252) and tTau/Aβ₄₂ (0.258) in Elecsys demonstrated the highest areas under the curve (0.97 and 0.96) and predictive values (96.6% for both) for detecting amyloid-PET abnormalities. No cases of abnormal amyloid PET status were found without concurrent abnormal CSF biomarkers when considering Elecsys Aβ₄₂ and the pTau₁₈₁/Aβ₄₂ ratio simultaneously. In addition, previously established cutoffs for combined ratios effectively differentiated amyloid PET status in our samples.

Conclusions: This study demonstrated the utility of Elecsys-measured CSF AD biomarkers in agreement with amyloid-PET classification in the Korean population. The pTau₁₈₁/Aβ₄₂ and tTau/Aβ₄₂ ratios were the most accurate in detecting amyloid-PET (+), with Elecsys showing higher accuracy than ELISA. The study also supported the applicability of common cutoffs from Western countries for these biomarkers in our samples.

Dynamic light scattering (DLS) spectroscopy measures changes in the Brownian movement of particles at the molecular level. Since the retina of the eye is a neural tissue and an outgrowth of the brain, a clinical instrument was developed capable of making DLS measurements from the retina in patients with mild cognitive impairment undergoing positron emission tomography nuclide imaging for the presence of cerebral amyloid.