Amyloid Burden In Patients Research Articles

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease.

Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical features increasing AD likelihood (SCD+). Amyloid-PET information ([18F]Flutemetamol or [18F]Florbetaben) of individuals with SCD+, mild cognitive impairment (MCI), and AD were retrieved from the AMYPAD-DPMS cohort, a multicenter randomized controlled study. Group classification was based on the recommendations by the SCD-I and NIA-AA working groups. Amyloid PET images were acquired within 8 months after initial screening and processed with AMYPYPE. Amyloid load was based on global Centiloid (CL) values. Educational level was indexed by formal schooling and subsequent higher education in years. Using linear regression analysis, the main effect of education on CL values was tested across the entire cohort, followed by the assessment of an education-by-diagnostic-group interaction (covariates: age, sex, and recruiting memory clinic). To account for influences of non-AD pathology and comorbidities concerning the tested amyloid-education association, we compared white matter hyperintensity (WMH) severity, cardiovascular events, depression, and anxiety history between lower-educated and higher-educated groups within each diagnostic category using the Fisher exact test or χ2 test. Education groups were defined using a median split on education (Md = 13 years) in a subsample of the initial cohort, for whom this information was available. Across the cohort of 212 individuals with SCD+ (M(Age) = 69.17 years, F 42.45%), 258 individuals with MCI (M(Age) = 72.93, F 43.80%), and 195 individuals with dementia (M(Age) = 74.07, F 48.72%), no main effect of education (ß = 0.52, 95% CI -0.30 to 1.58), but a significant education-by-group interaction on CL values, was found (p = 0.024) using linear regression modeling. This interaction was driven by a negative association of education and CL values in the SCD+ group (ß = -0.11, 95% CI -4.85 to -0.21) and a positive association in the MCI group (ß = 0.15, 95% CI 0.79-5.22). No education-dependent differences in terms of WMH severity and comorbidities were found in the subsample (100 cases with SCD+, 97 cases with MCI, 72 cases with dementia). Education may represent a factor oppositely modulating subjective awareness in preclinical stages and objective severity of ongoing neuropathologic processes in clinical stages.

Association between QRS voltages and amyloid burden in patients with cardiac amyloidosis.

Association between QRS voltages and amyloid burden in patients with cardiac amyloidosis.

Effect of white matter tract microstructural integrity on gamma entrainment using flickering light stimulation

AbstractBackgroundAlthough gamma entrainment using flickering light stimulation (FLS), which was found to reduce Alzheimer’s disease pathologies in mice model, it failed to reduce cerebral amyloid burden in patients with AD or mild cognitive impairment. We investigated the optimal parameters of the FLS for entraining gamma waves in older adults in their brain may be influenced by white‐matter tract microstructural integrity (WMMSI) in humans.MethodWe enrolled 31 cognitively normal volunteers aged ≥ 65 years and measured resting‐state electroencephalography and the steady‐state visually evoked potential (SSVEP) of gamma rhythms induced by optimal FLS. We analyzed the spectral power change of the electroencephalogram induced by FLS using event‐related synchronization (ERS) and the propagation of gamma rhythms from the visual cortex to other brain regions using spectral Granger causality (sGC). Diffusion tensor images were acquired, and the microstructural integrity of white‐matter tracts of interest was measured. We investigated the relationship between white matter integrity and entrainment and propagation using fractional anisotropy (FA).ResultAfter excluding five participants with SSVEP deficit, 26 participants were included in the final analysis. The lowest quartile group of the FA of the left posterior thalamic radiation exhibited a significantly lower ERS of gamma rhythms in the visual cortex than the second‐to‐highest quartile group (p = 0.045). In the multiple linear regression analyses, the effects of the FA of the middle longitudinal fasciculus and superior longitudinal fasciculus 3 on the sGC of the gamma rhythm connectivity from the occipital to the temporal, central, and frontal regions were statistically significant in both hemispheres (p < 0.05).ConclusionThese findings suggest intact WMMSI may be required for proper gamma entrainment using FLS. Therefore, future clinical trials on gamma entrainment using FLS needs to consider WMMSI for participant selection.

Enrolling patients in Cardiac Amyloid Reaching for Extended Survival (CARES) trials: Two placebo-controlled, double-blind, randomized, international phase 3 trials assessing CAEL-101 in patients with Mayo stage IIIa or stage IIIb AL amyloidosis.

TPS8071 Background: Light-chain (AL) amyloidosis is a rare, progressive, systemic disorder caused by plasma cell dyscrasia (PCD). Amyloid fibrils deposit in organs leading to progressive organ damage and death. Prognosis is poor for patients with cardiac involvement. Median survival is 24 and 4 months for patients in Mayo Stages IIIa and IIIb (based on the 2013 European Modification of the Mayo 2004 staging criteria), respectively. The standard of care (SoC) is anti-PCD therapy to suppress amyloid fibril generation. As yet, there are no therapies that remove deposited fibrils. CAEL-101 is a monoclonal antibody that binds to amyloid fibrils and may facilitate their systemic removal, improve organ function, and patient survival. These ongoing trials will evaluate the efficacy and safety of CAEL-101 as first-in-class treatment to reduce amyloid burden in patients with cardiac AL amyloidosis. Notably, 301 (Mayo Stage IIIb) is the first randomized, placebo-controlled efficacy clinical trial to formally assess the effects of a pharmacological in this severely ill population. Because the median expected survival for Mayo Stage IIIb patients is far shorter than for Mayo Stage IIIa patients, the resulting sample size required for the Mayo Stage IIIb study is less than for the Mayo Stage IIIa study. The objective of these trials is to evaluate the efficacy and safety of CAEL-101 when administered concurrently with SoC anti-PCD therapy in treatment-naïve patients with cardiac AL amyloidosis in Mayo Stages IIIb (NCT04504825; 301) or IIIa (NCT04512235; 302). Methods: These international, multicenter, double-blind, randomized, phase 3 trials, initiated in 2020, are enrolling patients at > 100 sites in > 20 countries. Newly diagnosed adults with AL amyloidosis stage IIIb or IIIa measurable hematologic disease, and histopathological diagnosis of amyloidosis with cardiac involvement are eligible. Patients with other forms of amyloidosis, symptomatic orthostatic hypotension, or supine systolic blood pressure < 90 mm Hg are ineligible. Patients in Mayo Stages IIIb (N = 124) and IIIa (N = 267) are being randomized 2:1 to receive once-weekly IV infusions of CAEL-101 (1000 mg/m2) or placebo for 4 weeks, followed by maintenance dosing every 2 weeks. In these event-driven studies, treatment will continue to a minimum of 101 and 79 events for 301 and 302, respectively. Patients will receive concurrent institutional SoC anti-PCD therapy at the discretion of the investigator. Overall survival (primary endpoint) will be analyzed via time-to-event log-rank statistics. Secondary endpoints include functional outcomes, quality of life, and echocardiography. Clinical trial information: NCT04504825 , NCT04512235 .

Brain Amyloid in Sporadic Young Onset Alzheimer's Disease.

Controversy exists as to the role of the amyloid-β (Aβ) peptide in the pathophysiology of Alzheimer's disease (AD). To clarify the effect of age on Aβ deposition in sporadic AD by exploring the degree of amyloid burden in patients with sporadic young onset AD (YOAD). Patients were diagnosed with YOAD with dementia starting before the age of 65 years (N = 42; males = 20, females = 22). A cross-sectional analysis of amyloid binding using positron emission tomography (PET) imaging was performed using the C-Pittsburgh Compound B (PiB). The global standardized uptake value ratios (gSUVR) were examined using the Wilcoxon two-sample test, as were the cognitive scores between disease and healthy control populations. Differences in PiB retention in different anatomical areas were compared using the Kruskal-Wallis test. The contrast in APOE genotyping between groups was calculated with Fisher's Exact Test. Women had a median gSUVR = 2.68±0.73 and 73% had at least one APOE ɛ4 allele. Men had gSUVR = 2.37±0.54, with 80% having at least one APOE ɛ4 allele. The gSUVRs were significantly higher than the control populations for men and women and had significantly greater frequency of APOE ɛ4. Men and women analyzed together had significantly greater amyloid burden and APOE ɛ4 allele frequencies than controls, but no differences existed between them in gSUVR nor in the anatomical distribution of amyloid uptake. Men and women with YOAD have greater amyloid uptake than controls and have more APOE ɛ4 alleles. Our findings suggest that the Aβ peptide is operational in young onset dementia and driven by the APOE ɛ4 allele.

Efficacy of probucol on cognitive function in Alzheimer’s disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study)

IntroductionPreclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid beta (Aβ) in the peripheral circulation is causally related to the development of Alzheimer’s disease (AD)....

Cognitive outcomes of anti‐amyloid‐β monoclonal antibodies in patients with Alzheimer's disease: A systematic review and meta‐analysis of randomized controlled trials

AbstractBackgroundFor the last 20 years, the amyloid‐beta (Aβ) cascade hypothesis has been dominant in the research of disease‐modifying therapeutics, with spent of financial and clinical resources in potential drugs targeting Aβ peptide production or clearance. (1) In this context, monoclonal antibodies targeting beta‐amyloid (Aβ‐mAbs) are being tested to reduce the amyloid burden in patients with Alzheimer’s Disease (AD). (2) However, the cognitive impact of Aβ‐mAbs remains controversial. (3) We aim to evaluate the conflicting results of previous studies using a meta‐analysis.MethodWe searched PubMed, Embase, and Cochrane databases, following until April 2021, using the search terms: ''Alzheimer's disease'' OR ''dementia'' cross‐referenced with ''monoclonal antibodies'', considering the synonyms. Eligible articles were randomized clinical trials with Aβ‐mAbs that reported cognitive outcomes. The cognitive function was assessed by Alzheimer’s Disease Assessment Scale (ADAS‐cog) and Mini‐Mental State‐Exam (MMSE). We performed a meta‐analysis comparing mAbs and placebo, considering a minimal significant clinical change of 3 points in ADAS‐Cog and 2 points in MMSE.ResultWe found 12 eligible studies in 443 identified records, involving 6736 patients, mean age 71.4 ± 2. We found a small benefit in cognitive outcomes in patients treated with Aβ‐mAbs: ADAS‐Cog: mean difference (MD) = ‐ 0.65; 95% CI (‐1.05 to ‐ 0.26); I² = 12%; (p = 0.001) and MMSE: MD = 0.40; 95% CI (0.18 to 0.63); I² = 10%; (p = 0.0004). The Funnel plot and Egger’s test did not show publication bias. MD was below the minimal clinically relevant change in both scales.ConclusionAβ‐mAbs may have a positive cognitive benefit in AD patients. However, the impact magnitude is small, not reaching minimal clinically relevant change for these scales.

Safety and Tolerability of Cael-101 in Combination with Anti-Plasma Cell Dyscrasia Therapy in Patients with AL Amyloidosis: 1-Year Results from an Open-Label Phase 2 Trial

Safety and Tolerability of Cael-101 in Combination with Anti-Plasma Cell Dyscrasia Therapy in Patients with AL Amyloidosis: 1-Year Results from an Open-Label Phase 2 Trial

Cardiac Amyloid Reaching for Extended Survival (CARES): Study Design of Two Placebo-Controlled, Double-Blind, Randomized, International Phase 3 Trials Assessing Cael-101 in Patients with Mayo Stage Iiia or Stage IIIb AL Amyloidosis

Cardiac Amyloid Reaching for Extended Survival (CARES): Study Design of Two Placebo-Controlled, Double-Blind, Randomized, International Phase 3 Trials Assessing Cael-101 in Patients with Mayo Stage Iiia or Stage IIIb AL Amyloidosis

Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Patients With Diabetes and AD-Related Cognitive Impairment.

To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer disease-related cognitive impairment (ADCI). We retrospectively reviewed 282 patients with ADCI with positive 18F-florbetaben amyloid PET images. Patients were classified into 3 groups according to prior diagnosis of diabetes and DPP-4i use: diabetic patients being treated with (ADCI-DPP-4i+, n = 70) or without DPP-4i (ADCI-DPP-4i-, n = 71) and nondiabetic patients (n = 141). Multiple linear regression analyses were performed to determine intergroup differences in global and regional amyloid retention using standardized uptake value ratios calculated from cortical areas. We assessed longitudinal changes in Mini-Mental State Examination (MMSE) score using a linear mixed model. The ADCI-DPP-4i+ group had lower global amyloid burden than the ADCI-DPP-4i- group (β = 0.075, SE = 0.024, p = 0.002) and the nondiabetic ADCI group (β = 0.054, SE = 0.021, p = 0.010) after adjusting for age, sex, education, cognitive status, and APOE ε4 carrier status. The ADCI-DPP-4i+ group had lower regional amyloid burden in temporo-parietal areas than either the ADCI-DPP-4i- group or the nondiabetic ADCI group. The ADCI-DPP-4i+ group showed a slower longitudinal decrease in MMSE score (β = 0.772, SE = 0.272, p = 0.005) and memory recall subscore (β = 0.291, SE = 0.116, p = 0.012) than the ADCI-DPP-4i- group. These findings suggest that DPP-4i use is associated with low amyloid burden and favorable long-term cognitive outcome in diabetic patients with ADCI.

MRI-Visible Perivascular Spaces in the Centrum Semiovale Are Associated with Brain Amyloid Deposition in Patients with Alzheimer Disease-Related Cognitive Impairment.

The association of perivascular spaces in the centrum semiovale with amyloid accumulation among patients with Alzheimer disease-related cognitive impairment is unknown. We evaluated this association in patients with Alzheimer disease-related cognitive impairment and β-amyloid deposition, assessed with [18F] florbetaben PET/CT. MR imaging and [18F] florbetaben PET/CT images of 144 patients with Alzheimer disease-related cognitive impairment were retrospectively evaluated. MR imaging-visible perivascular spaces were rated on a 4-point visual scale: a score of ≥3 or <3 indicated a high or low degree of MR imaging-visible perivascular spaces, respectively. Amyloid deposition was evaluated using the brain β-amyloid plaque load scoring system. Compared with patients negative for β-amyloid, those positive for it were older and more likely to have lower cognitive function, a diagnosis of Alzheimer disease, white matter hyperintensity, the Apolipoprotein E ε4 allele, and a high degree of MR imaging-visible perivascular spaces in the centrum semiovale. Multivariable analysis, adjusted for age and Apolipoprotein E status, revealed that a high degree of MR imaging-visible perivascular spaces in the centrum semiovale was independently associated with β-amyloid positivity (odds ratio, 2.307; 95% CI, 1.036-5.136; P = .041). A high degree of MR imaging-visible perivascular spaces in the centrum semiovale independently predicted β-amyloid positivity in patients with Alzheimer disease-related cognitive impairment. Thus, MR imaging-visible perivascular spaces in the centrum semiovale are associated with amyloid pathology of the brain and could be an indirect imaging marker of amyloid burden in patients with Alzheimer disease-related cognitive impairment.

Interhemispheric distribution of amyloid and small vessel disease burden in cerebral amyloid angiopathy-related intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating presentation of cerebral amyloid angiopathy (CAA), but the mechanisms leading from vascular amyloid deposition to ICH are not well known. Whether amyloid burden and magnetic resonance imaging (MRI) markers of small vessel disease (SVD) are increased in the ICH-affected hemisphere compared to the ICH-free hemisphere in patients with a symptomatic CAA-related ICH was investigated. Eighteen patients with CAA-related ICH and 18 controls with deep ICH who underwent brain MRI and amyloid positron emission tomography using 18 F-florbetapir were prospectively enrolled. In each hemisphere amyloid uptake using the standardized uptake value ratio and the burden of MRI markers of SVD including cerebral microbleeds, chronic ICH, cortical superficial siderosis, white matter hyperintensities and lacunes were evaluated. Interhemispheric comparisons were assessed by non-parametric matched-pair tests within each patient group. Amyloid burden was similarly distributed across the brain hemispheres in patients with CAA-related ICH (standardized uptake value ratio 1.11 vs. 1.12; P=0.74). Cortical superficial siderosis tended to be more common in the ICH-affected hemisphere compared to the ICH-free hemisphere (61% vs. 33%; P=0.063). Other MRI markers of SVD did not differ across brain hemispheres. In controls with deep ICH, no interhemispheric difference was observed either for amyloid burden or for MRI markers of SVD. Brain hemorrhage does not appear to be directly linked to amyloid burden in patients with CAA-related ICH. These findings provide new insights into the mechanisms leading to hemorrhage in CAA.

Behavioral circadian rhythm is associated with cognition, medial temporal lobe volume and cortical amyloid burden in patients with cognitive impairment

Behavioral circadian rhythm is associated with cognition, medial temporal lobe volume and cortical amyloid burden in patients with cognitive impairment

Dietary intake of pantothenic acid is associated with cerebral amyloid burden in patients with cognitive impairment.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the deposition of amyloid-β peptide (Aβ) in diffuse and neuritic plaques. Previous research has suggested that certain vitamins may prevent this process. In the present study, we evaluated the relationship between vitamin intake and cerebral Aβ burden in patients with cognitive impairment. This study included 19 patients with subjective cognitive impairment and 30 patients with mild cognitive impairment. All patients underwent brain MRI and 18F-florbetaben positron emission tomography. The Food Frequency Questionnaire was used to evaluate dietary intake of the 15 vitamins. Intake of vitamin B6 (p = 0.027), vitamin K (p = 0.042), vitamin A (p = 0.063), riboflavin (p = 0.063), β-carotene (p = 0.081), pantothenic acid (p = 0.092), and niacin (p = 0.097) was higher in the Aβ-positive group than in the Aβ-negative group. Multivariate linear regression analysis revealed that pantothenic acid intake was an independent determinant of cerebral Aβ burden (β = 0.287, p = 0.029). No significant correlations were observed between cerebral Aβ burden and the intake of other vitamins. Our findings demonstrated that pantothenic acid intake may be associated with increased cerebral Aβ burden in patients with cognitive impairment. These results may offer insight into potential strategies for AD prevention.

Correlation of Cerebral Microbleed Distribution to Amyloid Burden in Patients with Primary Intracerebral Hemorrhage

The underlying pathology of cerebral microbleeds (CMBs) with mixed lobar and deep distribution remains contentious. The aim of this study was to correlate CMBs distribution to β-amyloid burden in patients with primary intracerebral hemorrhage (ICH). Fourty-seven ICH patients underwent magnetic resonance susceptibility-weighted imaging and 11C-Pittsburgh Compound B positron emission tomography. The amyloid burden was expressed as standardized uptake value ratio with reference to cerebellum, and presented as median (interquartile range). Patients were categorized into the lobar, mixed (both lobar and deep regions), and deep types of CMB. Comparing the lobar (17%), mixed (59.6%) and deep (23.4%) CMB types, the global amyloid burden was significantly higher in the mixed type than the deep type (1.10 [1.03–1.25] vs 1.00 [0.97–1.09], p = 0.011), but lower than in the lobar type (1.48 [1.18–1.50], p = 0.048). On multivariable analysis, the ratio of lobar to deep CMB number was positively correlated with global (p = 0.028) and occipital (p = 0.031) amyloid burden. In primary ICH, patients with lobar and mixed CMB types are associated with increased amyloid burden than patients with deep type. The ratio of lobar to deep CMB number is an independent indicator of cerebral β-amyloid deposition.

Abstract 123: Correlation of Cerebral Microbleeds Distribution to Amyloid Burden in Patients With Spontaneous Intracerebral Hemorrhage

Background and Purpose: The diagnosis of cerebral amyloid angiopathy (CAA) mainly depends on clinical estimation such as the location of ICH or cerebral microbleeds (CMBs). We aimed to use [11C]PiB PET to image cerebral β-amyloid deposition and validate the CAA diagnosis in patients with ICH. Methods: Twenty six patients with spontaneous ICH received cerebral [11C]PiB PET to measure the amyloid burden and 3-T magnetic resonance susceptibility weighted imaging (SWI) to analyze the distribution of CMBs. Seven patients with Alzheimer’s disease (AD) and 7 healthy subjects were included for a comparison. The lobar amyloid burden was expressed as average standardized uptake value (SUV) using the commercial software package PMOD. The number of CMBs was counted using the Microbleed Anatomical Rating Scale (MARS). Results: The amyloid burden in patients with ICH (0.72±0.27) was significantly higher than that of heathy controls (0.47±0.17, p=0.03), but lower than that of AD patients (1.31±0.38, p=0.001). The amyloid burden was not significantly different between the patients with cortico-subcortical (frontal, temporal, parietal and occipital lobes) ICH and those with deep (putamen, thalamus, caudate and cerebellum) ICH (0.77±0.32 vs. 0.67±0.20, p=0.66). CMBs were present in 23 of 26 patients (88.5%). The amyloid burden was higher in patients with CMBs located predominantly at the cortico-subcortical areas (n=8) than those with CMBs located predominantly at the deep regions (n=9) (0.96±0.30 vs. 0.54±0.13, p=0.009). The ratio of cortico-subcortical CMB number to deep CMB number was positively correlated with the amyloid burden (γ=0.65, p=0.004). Conclusion: The distribution of CMBs is a better indicator than the ICH location to predict cerebral β-amyloid deposition in patients with ICH.

Amyloid burden in patients with mild cognitive impairment is associated with elevated blood pressure during sleep and altered cerebral pressure-flow dynamics

Amyloid burden in patients with mild cognitive impairment is associated with elevated blood pressure during sleep and altered cerebral pressure-flow dynamics

Investigational Alzheimer Drugs Fail to Improve Cognition or Function in Phase III Trials

The amyloid hypothesis of Alzheimer disease (AD) suggests that overproduction or abnormal clearance of the amyloid-beta (Aβ) peptide is critical to the early pathogenesis of AD. Two investigational monoclonal antibodies designed to decrease amyloid burden in patients with AD were recently assessed in phase 3 clinical trials. Both antibodies were tested in two industry-sponsored trials. In one trial, researchers randomly administered intravenous bapineuzumab — which recognizes both soluble and aggregated Aβ — or placebo periodically for 78 weeks to patients with mild-to-moderate AD; 1121 patients were APOE ℇ4 carriers and 1331were noncarriers. At the conclusion of the trials, …

A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition

BackgroundIdentification and quantification of fibrillar amyloid in brain using positron emission tomography (PET) imaging and Amyvid™ ([18 F] Amyvid, [18 F] florbetapir, 18 F-AV-45) was recently approved by the US Food and Drug Administration as a clinical tool to estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia. Imaging with [18 F] florbetapir offers in vivo confirmation of the presence of cerebral amyloidosis and may increase the accuracy of the diagnosis and likely cause of cognitive impairment (CI) or dementia. Most importantly, amyloid imaging may improve certainty of etiology in situations where the differential diagnosis cannot be resolved on the basis of standard clinical and laboratory criteria.ResultsA consecutive case series of 30 patients (age 50-89; 16 M/14 F) were clinically evaluated at a cognitive evaluation center of urban dementia center and referred for [18 F] florbetapir PET imaging as part of a comprehensive dementia workup. Evaluation included neurological examination and neuropsychological assessment by dementia experts. [18 F] florbetapir PET scans were read by trained nuclear medicine physicians using the qualitative binary approach. Scans were rated as either positive or negative for the presence of cerebral amyloidosis. In addition to a comprehensive dementia evaluation, post [18 F] florbetapir PET imaging results caused diagnoses to be changed in 10 patients and clarified in 9 patients. Four patients presenting with SCI were negative for amyloidosis. These results show that [18 F] florbetapir PET imaging added diagnostic clarification and discrimination in over half of the patients evaluated.ConclusionsAmyloid imaging provided novel and essential data that: (1) caused diagnosis to be revised; and/or (2) prevented the initiation of incorrect or suboptimal treatment; and/or (3) avoided inappropriate referral to an anti-amyloid clinical trial.

Amyloid Burdens in MCI of Alzheimer's Disease Versus Subcortical Vascular Dementia (S34.004)

Objective: We aimed to compare amyloid burden between patients with amnestic MCI (aMCI) and subcortical vascular MCI(svMCI). Background Most studies on mild cognitive impairment (MCI) have been focused on aMCI which is the preclinical stage of Alzheimer9s disease (AD). In contrast, only a few studies have involved patients in the preclinical stages of subcortical vascular dementia(svMCI). A recent study using Pittsburg compound-B (PiB) PET suggested that over 30% of patients who had been clinically diagnosed with SVaD showed significant amyloid deposits. However, to our knowledge, there has been no study investigating amyloid burden in patients with svMCI. We aimed to compare amyloid burden between patients with aMCI and svMCI, and to evaluate the effects of amyloid burden on cognition in patients with svMCI. Design/Methods: Participants consisted of 45 aMCI and 67 svMCI patients. All aMCI patients met Petersen9s criteria and all svMCI patients met Petersen9s criteria with some modifications that were previously described. Patients with svMCI had extensive white matter hyperintensities (WMH). All the patients underwent 3.0T MRI, 11C-Pittsburgh compound B (PiB) PET and detailed neuropsychological testing. Results: Twenty eight (62.2%) of the 45 patients with aMCI were positive PiB (PiB(+)), while twenty two (32.8%) of the 67 patients with svMCI were PiB(+). The mean uptake ratio of PiB was higher in aMCI (1.868 ± 0.512) than svMCI (1.504±0.402) (p Conclusions: Our findings suggested that patients with svMCI showed lower amyloid burdens than aMCI. We also found that amyloid burden affected memory dysfunction in patients with svMCI. Disclosure: Dr. Lee has nothing to disclose. Dr. Seo has nothing to disclose. Dr. Na has nothing to disclose.