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BACKGROUND: There are major challenges in determining the etiology of vascular cognitive impairment (VCI) clinically, especially in the presence of mixed pathologies, such as vascular and amyloid. Most recently, two criteria (American Heart Association/American Stroke Association (AHA/ASA) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)) have been proposed for the clinical diagnosis of VCI but have not as yet been validated using neuroimaging. AIMS: This study aims to determine whether the AHA/ASA and DSM-V criteria for VCI can distinguish between cases with predominantly vascular pathology and cases with mixed pathology. METHODS: A total of 186 subjects were recruited from a cross-sectional memory clinic-based study at the National University Hospital, Singapore. All subjects underwent clinical and neuropsychological assessment, magnetic resonance imaging (MRI) and carbon 11-labeled Pittsburgh Compound B ([11C] PiB) positron emission tomography (PET) scans. Diagnosis of the etiological subtypes of VCI (probable vascular mild cognitive impairment (VaMCI), possible VaMCI, non-VaMCI, probable vascular dementia (VaD), possible VaD, non-VaD) were performed following AHA/ASA and DSM-V criteria. Brain amyloid burden was determined for each subject with standardized uptake value ratio (SUVR) values ⩾1.5 classified as amyloid positive. RESULTS: Using κ statistics, both criteria had excellent agreement for probable VaMCI, probable VaD, and possible VaD (κ = 1.00), and good for possible VaMCI (κ = 0.71). Using the AHA/ASA criteria, the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) was significantly lower compared to possible VaMCI (26.7%), non-VaMCI (33.3%), possible VaD (73.3%), and non-VaD (76.2%) (p < 0.001). Similarly, using the DSM-V criteria, the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) was significantly lower compared to possible VaMCI (26.3%), non-VaMCI (32.1%), possible VaD (73.3%), and non-VaD (76.2%) (p < 0.001). In both criteria, there was good agreement in differentiating individuals with non-VaD and possible VaD, with significantly higher (p < 0.001) global [11C]-PiB SUVR, from individuals with probable VaMCI and probable VaD, who had predominant vascular pathology. CONCLUSION: The AHA/ASA and DSM-V criteria for VCI can identify VCI cases with little to no concomitant amyloid pathology, hence supporting the utility of AHA/ASA and DSM-V criteria in diagnosing patients with predominant vascular pathology. DATA ACCESS STATEMENT: Data supporting this study are available from the Memory Aging and Cognition Center, National University of Singapore. Access to the data is subject to approval and a data sharing agreement due to University policy.
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Purpose: Toxoplasma gondii is a parasite that is widely distributed around the globe and can cause brain inflammation, particularly in immunosuppressed patients such as those diagnosed with human immunodeficiency virus (HIV). This paper reviews the efficacy of azithromycin and pyrimethamine combination therapy for cerebral toxoplasmosis in patients with HIV. Methods: The scope of the studies included in this review was limited from 1992 to 2022, with studies primarily being randomized, controlled clinical trials available on online scientific journal databases. The authors screened eligible records for review, removing those that did not fit the inclusion and exclusion criteria. The risk of bias of the extracted data was analyzed through the Cochrane risk-of-bias tool for randomized trials. Results: A broad search of major online databases such as PubMed, Medline, Google Scholar, and Cochrane using keywords, limit fields, and Boolean operators yielded 3,130 articles. After thoroughly screening the search results, two studies were included in this review. Results from the studies included in the review demonstrate that the combination therapy of azithromycin and pyrimethamine is favorable for cerebral toxoplasmosis. However, the net response is less effective than the standard treatment regimen (pyrimethamine and sulfadiazine). Conclusion: The combination therapy of azithromycin and pyrimethamine is less effective than the standard treatment regimen for maintenance therapy for cerebral toxoplasmosis; thus, administering these medications for this indication must be met with caution.
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OBJECTIVE: To evaluate the association between brain amyloid ß (Aß) and cerebral small vessel disease (CSVD) markers, as well as their joint effect on cognition, in a memory clinic study. METHODS: A total of 186 individuals visiting a memory clinic, diagnosed with no cognitive impairment, cognitive impairment no dementia (CIND), Alzheimer dementia (AD), or vascular dementia were included. Brain Aß was measured by [11C] Pittsburgh compound B-PET global standardized uptake value ratio (SUVR). CSVD markers including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs) were graded on MRI. Cognition was assessed by neuropsychological testing. RESULTS: An increase in global SUVR is associated with a decrease in Mini-Mental State Examination (MMSE) in CIND and AD, as well as a decrease in global cognition Z score in AD, independent of age, education, hippocampal volume, and markers of CSVD. A significant interaction between global SUVR and WMH was found in relation to MMSE in CIND (P for interaction: 0.009), with an increase of the effect size of Aß (ß = -6.57 [-9.62 to -3.54], p < 0.001) compared to the model without the interaction term (ß = -2.91 [-4.54 to -1.29], p = 0.001). CONCLUSION: Higher global SUVR was associated with worse cognition in CIND and AD, but was augmented by an interaction between global SUVR and WMH only in CIND. This suggests that Aß and CSVD are independent processes with a possible synergistic effect between Aß and WMH in individuals with CIND. There was no interaction effect between Aß and lacunes or CMBs. Therefore, in preclinical phases of AD, WMH should be targeted as a potentially modifiable factor to prevent worsening of cognitive dysfunction.
