Increased levels of plasma amyloid-beta are related to cortical thinning and cognitive decline in cognitively normal elderly subjects

Llado-Saz, Sandra; Atienza, Mercedes; Cantero, José L.

doi:10.1016/j.neurobiolaging.2015.06.023

Cited by 43 publications

(32 citation statements)

References 67 publications

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“…The connection between these speeded measures that also tap into executive functioning are consistent with prior studies linking baseline processing speed/executive functioning scores and amyloid, whether assessed via plasma (31), cerebrospinal fluid (32), or PET imaging (29). However, to our knowledge, this is the first study examining practice effects on these tests and amyloid deposition via PET.…”

Section: Discussionsupporting

confidence: 81%

Short-Term Practice Effects and Amyloid Deposition: Providing Information Above and Beyond Baseline Cognition

Duff¹,

Hammers²,

Dalley³

et al. 2017

J Prev Alz Dis

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Background: Practice effects, which are improvements in cognitive test scores due to repeated exposure to testing materials, may provide information about Alzheimer’s disease pathology, which could be useful for clinical trials enrichment. Objectives: The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to amyloid deposition on neuroimaging. Participants: Twenty-seven, non-demented older adults (9 cognitively intact, 18 with mild cognitive impairment) received amyloid imaging with 18F-Flutemetamol, and two cognitive testing sessions across one week to determine practice effects. Results: A composite measure of 18F-Flutemetamol uptake correlated significantly with all seven cognitive tests scores on the baseline battery (r’s = -0.61 – 0.59, all p’s<0.05), with higher uptake indicating poorer cognition. Practice effects significantly added to the relationship (above and beyond the baseline associations) with 18F-Flutemetamol uptake on 4 of the 7 cognitive test scores (partial r’s = -0.45 – 0.44, p’s<0.05), with higher uptake indicating poorer practice effects. The odds ratio of being “amyloid positive” was 13.5 times higher in individuals with low practice effects compared to high practice effects. Conclusions: Short-term practice effects over one week may be predictive of progressive dementia and serve as an affordable screening tool to enrich samples for preventative clinical trials in Alzheimer’s disease.

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Section: Discussionsupporting

confidence: 81%

Short-Term Practice Effects and Amyloid Deposition: Providing Information Above and Beyond Baseline Cognition

Duff¹,

Hammers²,

Dalley³

et al. 2017

J Prev Alz Dis

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“…It may be that higher glucose levels lead to grey matter atrophy via cerebral glucose hypometabolism, which leads to neuronal injury, which has been shown to be independent of Aβ accumulation [48]. Although research has shown that cortical thinning occurs in the prodromal stages of several types of dementia (i.e., dementia with Lewy bodies, AD, and vascular dementia) [4,13,14, 35], few studies have investigated cortical thickness in a cognitively normal, healthy sample [17,34,42]. …”

Section: Discussionmentioning

confidence: 99%

Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults

Wennberg

Spira²,

Pettigrew³

et al. 2016

Journal of the Neurological Sciences

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Type II diabetes mellitus (DM) increases risk for cognitive decline and is associated with brain atrophy in older demented and non-demented individuals. We investigated (1) the cross-sectional association between fasting blood glucose level and cortical thickness in a sample of largely middle-aged, cognitively normal adults, and (2) whether these associations were modified by genes associated with both lipid processing and dementia. To explore possible modifications by genetic status, we investigated the interaction between blood glucose levels and the apolipoprotein E (APOE) ε4 allele and the translocase of the outer mitochondrial membrane (TOMM) 40 ′523 genotype on cortical thickness. Cortical thickness measures were based on mean thickness in a subset of a priori-selected brain regions hypothesized to be vulnerable to atrophy in Alzheimer's disease (AD) (i.e., ‘AD vulnerable regions’). Participants included 233 cognitively normal subjects in the BIOCARD study who had a measure of fasting blood glucose and cortical thickness measures, quantified by magnetic resonance imaging (MRI) scans. After adjustment for age, sex, race, education, depression, and medical conditions, higher blood glucose was associated with thinner parahippocampal gyri (B = −0.002; 95% CI −0.004, −0.0004) and temporal pole (B = −0.002; 95% CI −0.004, −0.0001), as well as reduced average thickness over AD vulnerable regions (B = −0.001; 95% CI −0.002, −0.0001). There was no evidence for greater cortical thinning in ε4 carriers of the APOE gene or in APOE ε3/3 individuals carrying the TOMM40 VL/VL genotypes. When individuals with glucose levels in the diabetic range (≥126 mg/dL), were excluded from the analysis, the associations between glucose levels and cortical thickness were no longer significant. These findings suggest that glucose levels in the diabetic range are associated with reduced cortical thickness in AD vulnerable regions as early as middle age.

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“…Study in animal models also shown increased LPO precedes amyloid plaque formation in a mice model of Alzheimer amyloidosis [46]. Some studies also shown abnormal and increased plasma Aβ levels seen in patients associated with cognitive decline and dementia [9], [10], [47], [48].…”

Section: Discussionmentioning

confidence: 94%

“…The increased Aβ levels in blood may in turn result in a stronger Aβ accumulation in cerebral region, which reinforces neuronal degeneration [8]. Plasma is the liquid portion of blood that suspends cells such as red blood cells, white blood cells, and platelets and studies demonstrated that quantification of plasma Aβ is considered as an emerging diagnostic tool for cognitive dysfunction and dementia [9], [10] and it has received strong interest as a reliable biomarker of neurodegenerative diseases, since blood sampling is much less invasive as lumbar puncturing that is currently required for CSF Aβ measurement [8], [11]. Study shown increased plasma Aβ42 peptide levels are associated with earlier onset of AD and increased threat of death [12].…”

Section: Introductionmentioning

confidence: 99%

Abnormal amyloid β 42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease

et al. 2017

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BackgroundCognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid β (Aβ) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aβ has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction. Increased oxidative stress leads to cause cleavage of APP and Aβ production. The aim of this study is to assess the antioxidant status and Aβ42 levels in plasma of CKD patients with cognitive dysfunction compared to CKD without cognitive dysfunction.MethodsA total of 60 subjects divided into 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment tests. To compare antioxidant status and Aβ42 levels in plasma, the following groups such as healthy subjects (n = 30), normocytic normochromic anemia (n = 30) and Alzheimer's disease (AD, n = 10) patients were also maintained. Plasma Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Reduced glutathione (GSH) and lipid peroxidation (LPO) were determined by spectrophotometrically. Aβ level was determined by immunoblotting method. The parameters were statistically compared with healthy, normocytic normochromic anemia and AD subjects.ResultsLike AD subjects, significantly increased Aβ and LPO level while decreased SOD, CAT, GPx and GSH levels were observed in plasma of CKD patients with cognitive dysfunction when compared to healthy, CKD without cognitive dysfunction and normocytic normochromic anemic subjects.ConclusionResults suggest that elevated plasma oxidative stress and Aβ were seen in CKD patients with cognitive dysfunction may be attributed to pathological changes within the brain.

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Increased levels of plasma amyloid-beta are related to cortical thinning and cognitive decline in cognitively normal elderly subjects

Cited by 43 publications

References 67 publications

Short-Term Practice Effects and Amyloid Deposition: Providing Information Above and Beyond Baseline Cognition

Short-Term Practice Effects and Amyloid Deposition: Providing Information Above and Beyond Baseline Cognition

Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults

Abnormal amyloid β 42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease

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