Synergistic Effects of Ischemia and β-Amyloid Burden on Cognitive Decline in Patients With Subcortical Vascular Mild Cognitive Impairment
(Impact Factor: 12.01).
02/2014; 71(4). DOI: 10.1001/jamapsychiatry.2013.4506
IMPORTANCE Cerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and β-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins. OBJECTIVE To determine the synergistic effects of β-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI). DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes. MAIN OUTCOMES AND MEASURES We measured β-amyloid burden using positron emission tomography with carbon 11-labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients' cognitive impairment. RESULTS On evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI. CONCLUSIONS AND RELEVANCE Most patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase β-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.
Available from: Abdulbasit Amin
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ABSTRACT: Although oxidative stress is characteristic of global vascular occlusion and cyanide toxicity, the pattern of cerebral metabolism reconditioning and rate of progression or reversal of neural tissue damage differ for both forms of ischemia. Thus, it is important to compare cognitive and motor functions in both models of ischemia involving cyanide treatment (CN) and vascular occlusion (VO).
Adult Wistar rats (N = 30) were divided into three groups; VO (n = 12), CN (n = 12) and Control-CO (n = 6). The CN was treated with 30 mg/Kg of potassium cyanide (KCN); VO was subjected to global vascular occlusion- both for duration of 10 days. The control (CO) was fed on normal rat chow and water for the same duration. At day 10, the test and control groups (CN, VO and CO) were subjected to motor function tests (Table edge tests and Open Field Test) and memory function tests (Y-Maze and Novel object recognition) while the withdrawal groups CN-I and VO-I were subjected to the same set of tests at day 20 (the withdrawal phase)
The results show that both cyanide toxicity and vascular occlusion caused a decline in motor and memory function when compared with the control. Also, the cyanide treatment produced a more rapid decline in these behavioural parameters when compared with the vascular occlusion during the treatment phase. After the withdrawal phase, cyanide treatment (CN-I) showed either an improvement or restoration of motor and memory function when compared to the CN and control. Withdrawal of vascular occlusion caused no improvement, and in some cases a decline in motor and memory function.
In conclusion, cyanide toxicity caused a decline in motor and memory function after the treatment while vascular occlusion caused no significant decline in cognition and motor function at this time. After the withdrawal phase, the effect of cyanide toxicity was reduced and significant improvements were observed in the behavioural tests (motor and cognitive), while a decline in these functions were seen in the vascular occlusion group after this phase.
Pathophysiology 09/2014; 21(3). DOI:10.1016/j.pathophys.2014.07.002
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ABSTRACT: FDG PET is a powerful method for detection of disease---related impairment of cerebral glucose metabolism in neurodegenerative diseases. It is of particular interest for early and differential diagnosis of dementia. Reading FDG PET scans requires training to recognise deviations from normal functional brain anatomy and its variations. This paper provides guidance for displaying FDG PET brain scans in a reproducible manner that allows reliable recognition of characteristic disease--related metabolic changes. It also describes typical findings in Alzheimer's disease, Frontotemporal Dementia and Dementia with Lewy Bodies and possible confounding factors, such as vascular changes and brain atrophy. It provides a brief overview on findings in other neurodegenerative diseases and addresses the potential and limitations of software packages for comparison of individual scans with reference data.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.. 11/2014; 58(4). · 2.03 Impact Factor
Available from: PubMed Central
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ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD.
BMC Medicine 12/2014; 12(1):130. DOI:10.1186/s12916-014-0130-5 · 7.25 Impact Factor
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