Journal of Alzheimer's disease reports最新文献

 Alzheimer's disease and cerebral amyloid angiopathy (CAA) are often associated. Amyloid accumulation within leptomeningeal and small/median-sized cerebral blood vessels in CAA results in vessel fragility, leading to spontaneous leptomeningeal bleeding, lobar intracerebral hemorrhage (ICH) and cerebral microbleeds. CAA is also associated with non-traumatic subdural hematoma. The role of CAA-related vessel fragility in hemorrhagic complications after trauma, brain surgery, and intracranial drain insertion in CAA is unknown. We present two sporadic CAA patients with intracranial drain-related ICH, probably due to different underlying mechanisms, related to indirect and direct CAA-associated vessel fragility.

Alzheimer's disease (AD) is the most common type of dementia, which is characterised by progressive memory loss and accumulation of hallmark markers amyloid-β (Aβ) and neurofibrillary tangles in the diseased brain. The current gold standard diagnostic methods have limitations of being invasive, costly, and not easily accessible. Thus, there is a need for new avenues, such as imaging the retina for early AD diagnosis. Sleep disruption is symptomatically frequent across preclinical and AD subjects. As circadian activity, such as the sleep-wake cycle, is linked to the retina, analysis of their association may be useful additions for achieving predictive AD diagnosis. In this narrative review, we provide an overview of human retina studies concerning the deposition of Aβ, the role of the retina in sleep-wake cycle, the disruption of sleep in AD, and to gather evidence for the associations between Aβ, the retina, and sleep. Understanding the mechanisms behind the associations between Aβ, retina, and sleep could assist in the interpretation of retinal changes accurately in AD.

The presence of parkinsonism features in primary progressive aphasia (PPA) is a subject of ongoing research. These features are usually more pronounced in the advanced stages of the disease, particularly in the non-fluent/agrammatic subtype, and are exceptionally rare in the logopenic variant (lvPPA). Here we report a case of a 63-year-old man presenting as language impairment, predominantly naming and word-finding difficulties, emerged alongside a left-sided internal tremor. Neurological examination revealed bilateral, left-side predominant rigidity, bradykinesia, and resting tremor. Notably, anosmia and constipation were present. Language assessments showed preserved single-word comprehension, object knowledge, and a minimal apraxia of speech, as well as sentence repetition issues. Neuroimaging and biomarker analysis supported a diagnosis of primary progressive logopenic aphasia with amyloid pathology co-existing with prominent and early parkinsonism. This case underlines the intricate relationship between language disorders, parkinsonism, and amyloid pathology in lvPPA.

Background: The Montreal Cognitive Assessment (MoCA) is recommended by the Movement Disorder Society for cognitive testing in movement disorders including Parkinson's disease (PD) and lewy body dementia. Few studies have compared cognitive screening instruments in these diseases, which overlap clinically.

Objective: To compare the MoCA and Quick Mild Cognitive Impairment (Qmci) screen in this population.

Methods: Patients attending memory and movement disorder clinics associated with a university hospital had the MoCA and Qmci screen performed and diagnostic accuracy compared with the area under the receiver operating characteristic curve (AUC). Duration and severity of movement disorders was assessed using the Unified PD Rating Scale (UPDRS).

Results: In total, 133 assessments were available, median age 74±5. Median education was 11±4 years and 65% were male. Median total UPDRS score was 37±26. Median Qmci screen was 51±27, median MoCA was 19±10. There were statistically significant differences in test scores between those with subjective symptoms but normal cognition, mild cognitive impairment (MCI) and dementia (p < 0.001). The Qmci screen had significantly greater accuracy differentiating normal cognition from MCI versus the MoCA (AUC 0.90 versus 0.72, p = 0.01). Both instruments had similar accuracy in identifying cognitive impairment and separating MCI from dementia. The median administration time for the Qmci screen and MoCA were 5.19 and 9.24 minutes (p < 0.001), respectively.

Conclusions: Both the MoCA and Qmci screen have good to excellent accuracy in a population with movement disorders experiencing cognitive symptoms. The Qmci screen was significantly more accurate for those with early symptoms and had a shorter administration time.

Background: Effect of stenosis of vertebrobasilar artery (VBA) on cognitive function is elusive.

Objective: To investigate association of cerebral hypoperfusion and poor collaterals with vascular cognitive impairment (VCI) in severe VBA stenosis patients.

Methods: We consecutively enrolled patients with severe VBA stenosis confirmed by digital subtraction angiography who underwent computed tomographic perfusion (CTP) and cognitive assessments. Patients were divided into poor or good collaterals groups according to the collateral circulation status, and were grouped into different perfusion groups according to CTP. Cognitive function was measured by Montreal Cognitive Assessment (MoCA), Clock Drawing Test, Stroop Color Word Test, Trail Making Test, Digital Span Test, Auditory Verbal Learning Test, and Boston Naming Test scales. The association of cerebral perfusion and collaterals with VCI were explored.

Results: Among 88 eligible patients, VCI occurred in 51 (57.9%) patients experienced. Poor collateral was present in 73 (83.0%) patients, and hypoperfusion in 64 (72.7%). Compared with normal perfusion patients, the odds ratio with 95% confidence interval for VCI was 12.5 (3.7-42.4) for overall hypoperfusion, 31.0 (7.1-135.5) for multiple site hypoperfusion, 3.3 (1.0-10.5) for poor collaterals, and 0.1 (0-0.6) for presence of posterior communicating artery (PcoA) compensated for posterior cerebral artery (PCA) and basilar artery (BA). Additionally, decreased scores of cognitive function tests occurred in patients with decompensated perfusion or poor collaterals.

Conclusions: Hypoperfusion and poor collaterals were positively associated with cognitive impairment in patients with severe VBA. However, PcoA compensated for the PCA and BA had a protective role in cognitive impairment development.

Background: The APP/PS1 mouse model recapitulates pathology of human Alzheimer's disease (AD). While amyloid-β peptide deposition and neurodegeneration are features of AD, the pathology may involve inflammation and impaired vascular regeneration.

Objective: This study evaluated inflammatory environments in the brain and bone marrow (BM), and the impact on brain microvascular density.

Methods: BM and frontal cortex from male nine-month-old APP/PS1 or the control C57Bl6/j mice were studied. Vascular density and inflammatory cells were evaluated in the sections of frontal cortex by immunohistochemistry. Different subsets of hematopoietic stem/progenitor cells (BM) and monocyte-macrophages were characterized by flow cytometry and by clonogenic assays. Myelopoietic or inflammatory factors were evaluated by real-time RT-PCR or by western blotting.

Results: CD34⁺ or CD31⁺ vascular structures were lower (p < 0.01, n = 6) in the frontal cortex that was associated with decreased number of Lin^-Sca-1⁺cKit⁺ vasculogenic progenitor cells in the BM and circulation (p < 0.02, n = 6) compared to the control. Multipotent progenitor cells MPP4, common lymphoid, common myeloid and myeloid progenitor cells were higher in the APP/PS1-BM compared to the control, which agreed with increased numbers of monocytes and pro-inflammatory macrophages. The expression of pro-myelopoietic factors and alarmins was higher in the APP/PS1 BM-HSPCs or in the BM-supernatants compared to the control. Frontal cortices of APP/PS1 mice showed higher number of pro-inflammatory macrophages (CD11b⁺F4/80⁺ or CD80⁺) and microglia (OX42⁺Iba1⁺).

Conclusions: These findings show that AD pathology in APP/PS1 mice is associated with upregulated myelopoiesis, which contributes to the brain inflammation and decreased vascularity.

We rediscovered a phenotype of AD known in the early 1900s as presbyophrenia, but then forgotten, and renamed as confabulation-misidentification phenotype. The phenotype includes diencephalic amnesia whose prototype is Korsakoff syndrome. The main features are anterograde and retrograde amnesia with marked disorientation and confabulation, executive impairments, reduced insight and attention deficits, misidentification, minor hallucination and other delusions, behavioral disturbances, and early anxiety. In this article, we summarize what we have discovered about the new phenotype and what is still missing to confirm this diencephalic variant of AD.

Background: There is now increasing evidence that type 2 diabetes mellitus (T2DM) is associated with Alzheimer's disease (AD). However, it is unclear whether the two are causally related.

Objective: To reveal the causal association between T2DM and AD, we performed a bidirectional Mendelian randomization (MR) analysis.

Methods: Genetic instrumental variables were systematically screened, and inverse-variance weighting, MR-Egger regression, weighted median, simple mode, and weighted mode were applied to assess the pathogenic associations between the two diseases, and sensitivity analyses were used to further validate the robustness of the results.

Results: The results of forward MR analysis with T2DM as the exposure were [OR = 0.998, 95% CI (0.975∼1.021), p = 0.857], and the results of reverse MR analysis with AD as the exposure were [OR = 0.966, 95% CI (0.934∼0.999), p = 0.043]. The results showed no significant association between T2DM and AD at the gene level (p < 0.025). Sensitivity analyses were consistent with the results of the main analysis, confirming the robustness of the study.

Conclusions: T2DM and AD may not be genetically causally associated.

Background: Excessive daytime sleepiness (EDS) and caudate nucleus volume alterations have been linked to Alzheimer's disease (AD), but their relationship remains unclear under the context of subjective cognitive decline (SCD).

Objective: This study aimed to investigate the relationship between EDS and caudate nucleus volume in patients with SCD.

Methods: The volume of entire brain was measured in 170 patients with SCD, including 37 patients with EDS and 133 non-EDS, from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Participants underwent a comprehensive assessment battery, including neuropsychological and clinical evaluations, blood tests, genetic analysis for APOE ɛ4, and structural MRI scans analyzed using the fully automated segmentation tool, volBrain.

Results: Patients with EDS had significantly increased volume in the total and left caudate nucleus compared to non-EDS. The most significant cognitive behavioral factor associated with caudate nucleus volume in the EDS was the Auditory Verbal Learning Test-recognition.

Conclusions: These findings suggest that EDS may be associated with alterations in caudate nucleus volume, particularly in the left hemisphere, in the context of SCD. Further research is necessary to understand the underlying mechanisms of this relationship and its implications for clinical management.

 A recent article by El Haj et al. provided evidence that ChatGPT could be a potential tool that complements the clinical diagnosis of various stages of Alzheimer's Disease (AD) as well as mild cognitive impairment (MCI). To reassess the accuracy and reproducibility of ChatGPT in the diagnosis of AD and MCI, we used the same prompt used by the authors. Surprisingly, we found that some of the responses of ChatGPT in the diagnoses of various stages of AD and MCI were different. In this commentary we discuss the possible reasons for these different results and propose strategies for future studies.