scholarly journals Homocysteic Acid in Blood Can Detect Mild Cognitive Impairment: A Preliminary Study

2020 ◽  
Vol 77 (2) ◽  
pp. 773-780
Author(s):  
Tohru Hasegawa ◽  
Yoshinori Kosoku ◽  
Yuka Sano ◽  
Hiroshi Yoshida ◽  
Chiaki Kudoh ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diagnostic Marker ◽  
Amyloid Β ◽  
Cost Effective ◽  
Negative Control ◽  
Necrosis Factor Alpha ◽  
Homocysteic Acid ◽  
Individual Level ◽  
Early Diagnostic

Background: In the treatment of Alzheimer’s disease (AD), it is thought to be most effective to intervene at the earliest and mildest stages. For diagnosis at the earliest and mildest stages, it is desirable to use a biomarker that can be detected by a minimally invasive, cost-effective technique. Recent research indicates the potential clinical usefulness of plasma amyloid-β (Aβ) biomarkers in predicting brain Aβ burden at an individual level. However, it is as yet unproven that accumulation of Aβ necessarily leads to the development of AD. Objective: Homocysteic acid (HCA) is useful as an early diagnostic marker for mild cognitive impairment (MCI), a pre-stage of AD. Methods: We measured the concentration of HCA, tumor necrosis factor alpha, cortisol, tau, and phosphorylated tau (p-tau) in patients’ plasma of 22 AD, 23 MCI, and 9 negative control (NC) cases. Results: Plasma HCA was shown to be very high in areas under the receiver operating characteristic curves (AUC), distinguished between MCI and NC; when 0.116μM was chosen as the analyte concentration cut-off, the sensitivity was 95.7% and the specificity was 70%. Conclusion: Our results suggest that plasma HCA may be a useful indicator as an early diagnostic marker for MCI. HCA seems to be upstream from neurodegeneration in the AD pathology because it is known that an overactive NMDA receptor promotes amyloid polymerization and tau phosphorylation in AD.

Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

2021 ◽  
pp. 1-13
Author(s):  
Dong Bai ◽  
Junting Fan ◽  
Mengyue Li ◽  
Cuixia Dong ◽  
Yiming Gao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Folic Acid ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Digit Span ◽  
Controlled Trial ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Double Blind ◽  
Full Scale Intelligence Quotient

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged >  60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p <  0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p <  0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

Physical Activity and Amyloid-β Brain Levels in Elderly Adults with Intact Cognition and Mild Cognitive Impairment

2015 ◽  
Vol 63 (8) ◽  
pp. 1634-1639 ◽  
Author(s):  
Philipe de Souto Barreto ◽  
Sandrine Andrieu ◽  
Pierre Payoux ◽  
Laurent Demougeot ◽  
Yves Rolland ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Elderly Adults ◽  
Brain Levels

scholarly journals Lipidomic Network of Mild Cognitive Impairment from the Mayo Clinic Study of Aging

2021 ◽  
pp. 1-11
Author(s):  
Xuewei Wang ◽  
Hai Bui ◽  
Prashanthi Vemuri ◽  
Jonathan Graff-Radford ◽  
Clifford R. Jack Jr ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Network Analysis ◽  
Mayo Clinic ◽  
Plasma Lipids ◽  
Amyloid Β ◽  
Cognitive Status ◽  
Correlation Network ◽  
Lipid Species ◽  
Clinic Study

Background: Lipid alterations contribute to Alzheimer’s disease (AD) pathogenesis. Lipidomics studies could help systematically characterize such alterations and identify potential biomarkers. Objective: To identify lipids associated with mild cognitive impairment and amyloid-β deposition, and to examine lipid correlation patterns within phenotype groups Methods: Eighty plasma lipids were measured using mass spectrometry for 1,255 non-demented participants enrolled in the Mayo Clinic Study of Aging. Individual lipids associated with mild cognitive impairment (MCI) were first identified. Correlation network analysis was then performed to identify lipid species with stable correlations across conditions. Finally, differential correlation network analysis was used to determine lipids with altered correlations between phenotype groups, specifically cognitively unimpaired versus MCI, and with elevated brain amyloid versus without. Results: Seven lipids were associated with MCI after adjustment for age, sex, and APOE4. Lipid correlation network analysis revealed that lipids from a few species correlated well with each other, demonstrated by subnetworks of these lipids. 177 lipid pairs differently correlated between cognitively unimpaired and MCI patients, whereas 337 pairs of lipids exhibited altered correlation between patients with and without elevated brain amyloid. In particular, 51 lipid pairs showed correlation alterations by both cognitive status and brain amyloid. Interestingly, the lipids central to the network of these 51 lipid pairs were not significantly associated with either MCI or amyloid, suggesting network-based approaches could provide biological insights complementary to traditional association analyses. Conclusion: Our attempt to characterize the alterations of lipids at network-level provides additional insights beyond individual lipids, as shown by differential correlations in our study.

scholarly journals Using a Digital Neuro Signature to measure longitudinal individual-level change in Alzheimer’s disease: the Altoida large cohort study

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Irene B. Meier ◽  
Max Buegler ◽  
Robbert Harms ◽  
Azizi Seixas ◽  
Arzu Çöltekin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Risk ◽  
Intraindividual Variability ◽  
Cognitive Test ◽  
Individual Level ◽  
Level Change ◽  
Neuropsychological Assessments

AbstractConventional neuropsychological assessments for Alzheimer’s disease are burdensome and inaccurate at detecting mild cognitive impairment and predicting Alzheimer’s disease risk. Altoida’s Digital Neuro Signature (DNS), a longitudinal cognitive test consisting of two active digital biomarker metrics, alleviates these limitations. By comparison to conventional neuropsychological assessments, DNS results in faster evaluations (10 min vs 45–120 min), and generates higher test-retest in intraindividual assessment, as well as higher accuracy at detecting abnormal cognition. This study comparatively evaluates the performance of Altoida’s DNS and conventional neuropsychological assessments in intraindividual assessments of cognition and function by means of two semi-naturalistic observational experiments with 525 participants in laboratory and clinical settings. The results show that DNS is consistently more sensitive than conventional neuropsychological assessments at capturing longitudinal individual-level change, both with respect to intraindividual variability and dispersion (intraindividual variability across multiple tests), across three participant groups: healthy controls, mild cognitive impairment, and Alzheimer’s disease. Dispersion differences between DNS and conventional neuropsychological assessments were more pronounced with more advanced disease stages, and DNS-intraindividual variability was able to predict conversion from mild cognitive impairment to Alzheimer’s disease. These findings are instrumental for patient monitoring and management, remote clinical trial assessment, and timely interventions, and will hopefully contribute to a better understanding of Alzheimer’s disease.

scholarly journals Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer’s Disease and Other Dementias

2020 ◽  
pp. 1-14
Author(s):  
Yi-Wen Bao ◽  
Anson C.M. Chau ◽  
Patrick Ka-Chun Chiu ◽  
Yat Fung Shea ◽  
Joseph S.K. Kwan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Subjective Cognitive Decline ◽  
Cognitively Impaired ◽  
Memory Clinic ◽  
Pet Ct

Background: With the more widespread use of 18F-radioligand-based amyloid-β (Aβ) PET-CT imaging, we evaluated Aβ binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. Objective: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer’s disease (AD), and 2) MCI from other non-AD dementias (OD). Methods: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). Results: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aβ binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. Conclusion: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

scholarly journals Association of brain amyloid-β with cerebral perfusion and structure in Alzheimer’s disease and mild cognitive impairment

Brain ◽  
2014 ◽  
Vol 137 (5) ◽  
pp. 1550-1561 ◽  
Author(s):  
Niklas Mattsson ◽  
Duygu Tosun ◽  
Philip S. Insel ◽  
Alix Simonson ◽  
Clifford R Jack ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cerebral Perfusion ◽  
Amyloid Β

Memory in individuals with mild cognitive impairment in relation to APOE and CSF Aβ42

2010 ◽  
Vol 22 (4) ◽  
pp. 598-606 ◽  
Author(s):  
Valgeir Thorvaldsson ◽  
Arto Nordlund ◽  
Ivar Reinvang ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Memory Performance ◽  
Interactive Effect ◽  
Amyloid Β ◽  
Total Sample ◽  
Increased Risk ◽  
Latent Curve ◽  
Latent Curve Models ◽  
Ε4 Allele

ABSTRACTBackground: The ε4 allele of the apolipoprotein E (APOE) gene and low levels of cerebrospinal fluid (CSF) amyloid β-proteins 42 (Aβ) have previously been associated with increased risk of cognitive decline in old age. In this study we examine the interaction of these markers with episodic memory in a sample identified as having mild cognitive impairment (MCI).Methods: The sample (N = 149) was drawn from the Gothenburg MCI study and measured according to three free recall tests on three occasions spanning over four years. Second-order Latent Curve Models (LCM) were fitted to the data.Results: Analyses accounting for age, gender, education, APOE, Aβ42, and interaction between APOE and Aβ42 revealed that the ε4 allele was significantly associated with level of memory performance in the presence of low Aβ42 values (≤452 ng/L). Associations between memory performance and Aβ42 were significant among the ε4 carriers but not among the non-carriers. The Aβ42 marker was, however, significantly associated with changes in memory over the study time period in the total sample.Conclusion: The findings support the hypothesis of an interactive effect of APOE and Aβ42 for memory decline in MCI patients.

The Modified Telephone-Administered Minnesota Cognitive Acuity Screen for Mild Cognitive Impairment

2018 ◽  
Vol 31 (3) ◽  
pp. 123-128 ◽  
Author(s):  
Sarah Pillemer ◽  
George D. Papandonatos ◽  
Cara Crook ◽  
Brian R. Ott ◽  
Geoffrey Tremont
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Characteristic Curve ◽  
Neuropsychological Testing ◽  
Cost Effective ◽  
Original Version ◽  
Modest Improvement ◽  
Highly Sensitive ◽  
Risk Of Progression ◽  
Administration Time

Objective: This study aimed to compare the sensitivity and specificity of a modified version of the Minnesota Cognitive Acuity Screen (MCAS-m), by adding learning and recognition memory components, to the original version MCAS to distinguish amnestic mild cognitive impairment (aMCI) from healthy controls (HCs). Methods/Design: A total of 30 individuals with aMCI and 30 HCs underwent neuropsychological testing, neurologic examination, laboratory, and brain imaging tests. Once diagnosis was confirmed, participants completed the MCAS and MCAS-m in counterbalanced order. Results: The average administration time was 12.6 minutes for the MCAS and 13.5 minutes for the MCAS-m. Receiver operating characteristic curve analyses showed that the MCAS-m demonstrated 97% sensitivity and 97% specificity for distinguishing between aMCI and HC versus 97% and 87%, respectively, for the original MCAS in this sample. Conclusions: Both the MCAS and the MCAS-m were highly sensitive when distinguishing between normal cognition and aMCI; however, the MCAS-m demonstrated a 10% increase in specificity compared to the original version. Improved specificity is particularly relevant to screening in larger community samples with lower base rates of MCI than clinic populations. This modified screening measure presents a brief and cost-effective tool for identifying MCI. Given the risk of progression from aMCI to Alzheimer disease dementia (AD), the MCAS-m represents a modest improvement in telephone-administered methods for the early detection of AD.

The Role of Apolipoprotein E ε4 in Early and Late Mild Cognitive Impairment

2021 ◽  
Vol 84 (6) ◽  
pp. 472-480
Author(s):  
Yulin Luo ◽  
Li Tan ◽  
Joseph Therriault ◽  
Hua Zhang ◽  
Ying Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Amyloid Β ◽  
Disease Assessment ◽  
Tau Pathology ◽  
Ε4 Allele ◽  
State Examination

<b><i>Background:</i></b> Apolipoprotein E (<i>APOE</i>) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of <i>APOE</i> ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of <i>APOE</i> ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer’s Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-β (Aβ). <b><i>Methods:</i></b> Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aβ42 and tau detection, <i>APOE</i> ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer’s disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of <i>APOE</i> ε4 and CSF tau levels and cognitive scores in persons with and without Aβ deposition (Aβ+ and Aβ−). <b><i>Results:</i></b> The prevalence of <i>APOE</i> ε4 is higher in EMCI and LMCI than in CN (<i>p</i> &#x3c; 0.001 for both), and in LMCI than in EMCI (<i>p</i> = 0.001). <i>APOE</i> ε4 allele was significantly higher in Aβ+ subjects than in Aβ− subjects (<i>p</i> &#x3c; 0.001). Subjects who had a lower CSF Aβ42 level and were <i>APOE</i> ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI. <b><i>Conclusions:</i></b> An <i>APOE</i> ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aβ. We conclude that <i>APOE</i> ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.

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