Introduction Retinal nerve fiber layer (RNFL) thinning, assessed by optical coherence tomography (OCT), has recently been reported in various dementias. Methods We conducted a systematic review and meta-analysis to investigate the diagnostic utility of RNFL thickness measurement using OCT in dementia (including Alzheimer's disease [AD] and mild cognitive impairment [MCI]) compared with healthy controls (HC). Results Seventeen studies comparing AD with HC (702 AD eyes and 790 HC eyes) were included, demonstrating a significant reduction in mean RNFL thickness in AD (weighted mean difference [WMD] 12.44, 95% confidence interval or CI [−16.64, −8.25], P <.0001). Five studies comparing MCI and HC (214 MCI eyes and 421 HC eyes) were included demonstrating a significant reduction in mean RNFL thickness in MCI (WMD −8.23, 95% CI [−14.00, −2.45], P =.005). No relevant studies were identified for other dementias. Discussion OCT measurement of RNFL thickness appears diagnostically useful in discriminating between AD, or MCI, and HC.
Background A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes. Methods For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 10 9 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3–6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis. Findings Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32–55) was lower than in the non-VITT group (57 years; 41–62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2–4) than non-VITT patients (two, 2–3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55...
BackgroundAmyloid imaging using fluorine 18–labeled tracers florbetapir, florbetaben, and flutemetamol has recently been reported in Alzheimer's disease (AD).MethodsWe systematically searched MEDLINE and EMBASE for relevant studies published from January 1980 to March 2014. Studies comparing imaging findings in AD and normal controls (NCs) were pooled in a meta-analysis, calculating pooled weighted sensitivity, specificity, and diagnostic odds ratio (OR) using the DerSimonian-Laird random-effects model.ResultsNineteen studies, investigating 682 patients with AD, met inclusion criteria. Meta-analysis demonstrated a sensitivity of 89.6%, a specificity of 87.2%, and an OR of 91.7 for florbetapir in differentiating AD patients from NCs, and a sensitivity of 89.3%, a specificity of 87.6%, and a diagnostic OR of 69.9 for florbetaben. There were insufficient data to complete analyses for flutemetamol.ConclusionsResults suggest favorable sensitivity and specificity of amyloid imaging with fluorine 18–labeled tracers in AD. Prospective studies are required to determine optimal imaging analysis methods and resolve outstanding clinical uncertainties.
Single-photon emission-computed tomography (SPECT) may potentially contribute to the diagnostic work up of patients with neurodegenerative dementia. This systematic review aims to establish the diagnostic utility of 99mTc-hexamethylpropyleneamine (99mTc-HMPAO) and 99mTc-ethylcysteine dimer SPECT in distinguishing between Alzheimer's disease (AD) and frontotemporal dementia (FTD), AD and vascular dementia (VD), AD and dementia with Lewy bodies (DLB), and AD and normal controls (NC). We searched MEDLINE and Embase databases via OVID for articles from January 1985 to May 2012 and identified additional studies from reviews and references. Of 755 studies, 49 studies met the inclusion and exclusion criteria for this systematic review; AD versus FTD (n=13), AD versus VD (n=18), AD versus DLB (n=5), and AD versus NC (n=18). We compiled relevant data and graded the studies with an internal and external validity criteria checklist. We pooled the studies with a clinical diagnosis and those using 99mTc-HMPAO SPECT in a meta-analysis, calculating the pooled weighted sensitivity, specificity, likelihood ratios, and diagnostic odds ratios using DerSimonian-Laird random-effects model. The pooled weighted sensitivity and specificity of 99mTc-HMPAO-SPECT in distinguishing clinically diagnosed AD from FTD are 79.7 and 79.9%, respectively, AD from VD are 74.5 and 72.4%, AD from DLB are 70.2 and 76.2%, and AD from NC are 76.1 and 85.4%. SPECT does have diagnostic value, particularly in differentiating Alzheimer's disease from frontotemporal dementia and normal controls; however, it should not be used in isolation, rather as an adjunct, and interpreted in the context of clinical information and paraclinical test results.
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