Plasma Amyloid-β Biomarker Associated with Cognitive Decline in Preclinical Alzheimer’s Disease

2020 ◽  
Vol 77 (3) ◽  
pp. 1057-1065
Author(s):  
Yen Ying Lim ◽  
Paul Maruff ◽  
Naoki Kaneko ◽  
James Doecke ◽  
Christopher Fowler ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Executive Function ◽  
Episodic Memory ◽  
High Performance ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Imaging Biomarkers ◽  
Cognitive Assessments ◽  
Positron Emission ◽  
The Relationship

Background: Using immunoprecipitation-mass spectrometry, we recently developed and validated a plasma composite biomarker for the assessment of amyloid-β (Aβ) levels. However, as yet, its relationship with clinical outcomes remains unclear. Objective: We aimed to examine the relationship between this plasma Aβ composite biomarker and cognitive function in cognitively normal older adults in two independent cohorts. Methods: Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study and the National Centre for Geriatrics and Gerontology (NCGG) study had undergone Aβ neuroimaging using positron emission tomography (PET), cognitive assessments and provided blood samples. We derived a high-performance plasma Aβ composite biomarker by immunoprecipitation with mass-spectrometry. Results: Both continuous and categorical measures of the plasma Aβ composite biomarker were significantly related to decline in episodic memory and executive function. The magnitude of effects of the plasma Aβ composite on episodic memory and executive function were comparable to that observed for the effects of PET Aβ levels on these same outcome measures. Conclusion: Several plasma Aβ biomarkers have been developed, but none have yet been applied to investigate their relationship with cognitive outcomes. Our results have important implications for the use of this biomarker in the detection of at-risk individuals.

scholarly journals Mind-Body Practice, Personality Traits, and Cognitive Performance: A 10-Year Study in US Adults

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 713-713
Author(s):  
Kallol Kumar Bhattacharyya ◽  
Gizem Hueluer ◽  
Debra Dobbs
Keyword(s):  
Executive Function ◽  
Cognitive Function ◽  
Episodic Memory ◽  
Personality Traits ◽  
The United States ◽  
Sociodemographic Factors ◽  
Cognitive Outcomes ◽  
Future Research ◽  
Big Five Personality ◽  
Negative Effect

Abstract It is widely established that physical activity is associated with better cognitive outcomes, and accumulating evidence suggests that mind-body practice (MBP) may yield similar benefits. Personality is related to both daily activities and cognition, but its role in the association between MBP and cognition is not well understood. The current study examines bidirectional temporal associations between personality traits, MBP, and cognition in healthy adults. We used data from waves 2 and 3 (2004-2014) of the Midlife in the United States (MIDUS) study from a total of 2,050 individuals (age: M=64 years, SD=11, range=42 to 92; 56% women). We applied a cross-lagged regression analysis to examine bidirectional effects between MBP, Big Five personality traits, and two cognitive domains (episodic memory and executive function) and controlled for sociodemographic factors, health, and functional status covariates in wave 2. After controlling for covariates, MBP was independently associated with a more favorable change in episodic memory, but not in executive function. Regarding cross-lagged effects of cognitive function, episodic memory was related to subsequent MBP and agreeableness, and executive function was related to subsequent MBP, openness, and conscientiousness. Agreeableness had a negative effect on subsequent executive function. The findings point toward bidirectional associations between cognitive function MBP, while there was no evidence for cross-lagged associations between personality and MBP. Future research should guide us whether MBP can counteract cognitive decline as an alternative and complementary practice and the role that personality can play in such interventions.

scholarly journals Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial

2020 ◽  
Vol 78 (3) ◽  
pp. 989-1010
Author(s):  
Gary E. Gibson ◽  
José A. Luchsinger ◽  
Rosanna Cirio ◽  
Huanlian Chen ◽  
Jessica Franchino-Elder ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Placebo Group ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Positron Emission

Background: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer’s disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation. Objective: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine. Methods: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome. Results: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOE ɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOE ɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002). Conclusion: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

scholarly journals No Influence of Age-Related Hearing Loss on Brain Amyloid-β

2021 ◽  
pp. 1-9
Author(s):  
Julia Z. Sarant ◽  
David C. Harris ◽  
Peter A. Busby ◽  
Christopher Fowler ◽  
Jurgen Fripp ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Pet Imaging ◽  
Clinical Sample ◽  
Amyloid Β ◽  
Carrier Status ◽  
Cognitive Assessments ◽  
Age Related ◽  
Positron Emission ◽  
Study Results ◽  
Study Participants

Background: Hearing loss is independently associated with a faster rate of cognitive decline in older adults and has been identified as a modifiable risk factor for dementia. The mechanism for this association is unknown, and there has been limited exploration of potential casual pathology. Objective: Our objective was to investigate whether there was an association between degree of audiometrically measured hearing loss (HL) and brain amyloid-β (Aβ) in a pre-clinical sample. Methods: Participants of the Australian Imaging and Biomarker Longitudinal Study (AIBL; n = 143) underwent positron emission tomography (PET) imaging and objective measurement of hearing thresholds within 5 years of imaging, as well as cognitive assessment within 2 years of imaging in this observational cohort study. Results: With one exception, study participants who had cognitive assessments within 2 years of their PET imaging (n = 113) were classified as having normal cognition. There was no association between cognitive scores and degree of hearing loss, or between cognitive scores and Aβ load. No association between HL and Aβ load was found once age was controlled for. As previously reported, positive Apolipoprotein E4 (APOE4) carrier status increased the risk of being Aβ positive (p = 0.002). Conclusion: Degree of HL was not associated with positive Aβ status.

Comorbidity of Cerebrovascular and Alzheimer’s Disease in Aging

2020 ◽  
Vol 78 (1) ◽  
pp. 321-334
Author(s):  
Ying Xia ◽  
Nawaf Yassi ◽  
Parnesh Raniga ◽  
Pierrick Bourgeat ◽  
Patricia Desmond ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrovascular Disease ◽  
Amyloid Β ◽  
Later Life ◽  
Imaging Biomarkers ◽  
Comorbid Condition ◽  
Cross Sectional ◽  
Positron Emission

Background: Cerebrovascular disease often coexists with Alzheimer’s disease (AD). While both diseases share common risk factors, their interrelationship remains unclear. Increasing the understanding of how cerebrovascular changes interact with AD is essential to develop therapeutic strategies and refine biomarkers for early diagnosis. Objective: We investigate the prevalence and risk factors for the comorbidity of amyloid-β (Aβ) and cerebrovascular disease in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing, and further examine their cross-sectional association. Methods: A total of 598 participants (422 cognitively normal, 89 with mild cognitive impairment, 87 with AD) underwent positron emission tomography and structural magnetic resonance imaging for assessment of Aβ deposition and cerebrovascular disease. Individuals were categorized based on the comorbidity status of Aβ and cerebrovascular disease (V) as Aβ–V–, Aβ–V+, Aβ+V–, or Aβ+V+. Results: Advancing age was associated with greater likelihood of cerebrovascular disease, high Aβ load and their comorbidity. Apolipoprotein E ɛ4 carriage was only associated with Aβ positivity. Greater total and regional WMH burden were observed in participants with AD. However, no association were observed between Aβ and WMH measures after stratification by clinical classification, suggesting that the observed association between AD and cerebrovascular disease was driven by the common risk factor of age. Conclusion: Our observations demonstrate common comorbid condition of Aβ and cerebrovascular disease in later life. While our study did not demonstrate a convincing cross-sectional association between Aβ and WMH burden, future longitudinal studies are required to further confirm this.

Insomnia Moderates the Relationship Between Amyloid-β and Cognitive Decline in Late-Life Adults without Dementia

2021 ◽  
pp. 1-10
Author(s):  
Wei Xu ◽  
Chen-Chen Tan ◽  
Juan-Juan Zou ◽  
Xi-Peng Cao ◽  
Lan Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Cognitive Disorders ◽  
Linear Mixed Effects ◽  
Positron Emission ◽  
Prodromal Ad ◽  
Neuropsychological Evaluations ◽  
The Relationship

Background: It is suggested that not all individuals with elevated Aβ will develop dementia or cognitive impairment. Environment or lifestyle might modulate the association of amyloid pathology with cognition. Insomnia is a risk factor of cognitive disorders including Alzheimer’s disease. Objective: To investigate if insomnia moderated the relationship between amyloid-β (Aβ) and longitudinal cognitive performance in non-demented elders. Methods: A total of 385 Alzheimer’s Disease Neuroimaging Initiative participants (mean age = 73 years, 48% females) who completed 4 + neuropsychological evaluations and a [18F] florbetapir positron emission tomography scan were followed up to 8 years. Linear mixed-effects regression models were used to examine the interactions effect between insomnia and Aβ on longitudinal cognitive sores, including four domains (memory [MEM], executive function [EF], language [LAN], and visuospatial function [VS]). Results: The Aβ-positive status (A+) but not insomnia independently predicted faster cognitive decline in all domains. Furthermore, the relationship between Aβ and cognitive decline was moderated by insomnia (MEM: χ 2 = 4.05, p = 0.044, EF: χ 2 = 4.38, p = 0.036, LAN: χ 2 = 4.56, p = 0.033, and VS: χ 2 = 4.12, p = 0.042). Individuals with both elevated Aβ and insomnia experienced faster cognitive decline than those with only elevated Aβ or insomnia. Conclusion: These data reinforced the values of insomnia management in preventing dementia, possibly by interacting Aβ metabolism. Future efforts are warranted to determine whether sleep improvement will postpone the onset of dementia, specifically among populations in stages of preclinical or prodromal AD.

Plasma homocysteine and cognitive decline in older hypertensive subjects

2011 ◽  
Vol 23 (10) ◽  
pp. 1607-1615 ◽  
Author(s):  
Sunil K. Narayan ◽  
Brian K. Saxby ◽  
Michael J. Firbank ◽  
John T. O'Brien ◽  
Frances Harrington ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Decline ◽  
The Elderly ◽  
Plasma Homocysteine ◽  
Cognitive Assessments ◽  
Computerized Assessment ◽  
Cognitive Domains ◽  
Memory And Attention ◽  
Independent Association ◽  
The Relationship

ABSTRACTBackground:Elevated plasma homocysteine concentrations have been associated with both cognitive impairment and dementia. However, it is unclear whether some cognitive domains are more affected than others, or if this relationship is independent of B12 and folate levels, which can also affect cognition. We examined the relationship between plasma homocysteine and cognitive decline in an older hypertensive population.Methods:182 older people (mean age 80 years) with hypertension and without dementia, were studied at one center participating in the Study on COgnition and Prognosis in the Elderly (SCOPE). Annual cognitive assessments were performed using a computerized assessment battery and executive function tests, over a 3–5 year period (mean 44 months). Individual rates of decline on five cognitive domains were calculated for each patient. End of study plasma homocysteine, folate and B12 concentrations were measured. The relationship between homocysteine levels and cognitive decline was studied using multivariate regression models, and by comparing high versus low homocysteine quartile groups.Results:Higher homocysteine showed an independent association with greater cognitive decline in three domains: speed of cognition (β = −27.33, p = 0.001), episodic memory (β = −1.25, p = 0.02) and executive function (β = −0.05, p = 0.04). The association with executive function was no longer significant after inclusion of folate in the regression model (β = −0.032, p = 0.22). Change in working memory and attention were not associated with plasma homocysteine, folate or B12. High homocysteine was associated with greater decline with a Cohen's d effect size of approximately 0.7 compared to low homocysteine.Conclusions:In a population of older hypertensive patients, higher plasma homocysteine was associated with cognitive decline.

scholarly journals Recent Developments in Positron Emission Tomography Tracers for Proteinopathies Imaging in Dementia

2022 ◽  
Vol 13 ◽  
Author(s):  
Ruiqing Ni ◽  
Roger M. Nitsch
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Parkinson's Disease ◽  
Amyloid Β ◽  
Emission Tomography ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Imaging Probes

An early detection and intervention for dementia represent tremendous unmet clinical needs and priorities in society. A shared feature of neurodegenerative diseases causing dementia is the abnormal accumulation and spreading of pathological protein aggregates, which affect the selective vulnerable circuit in a disease-specific pattern. The advancement in positron emission tomography (PET) biomarkers has accelerated the understanding of the disease mechanism and development of therapeutics for Alzheimer’s disease and Parkinson’s disease. The clinical utility of amyloid-β PET and the clinical validity of tau PET as diagnostic biomarker for Alzheimer’s disease continuum have been demonstrated. The inclusion of biomarkers in the diagnostic criteria has introduced a paradigm shift that facilitated the early and differential disease diagnosis and impacted on the clinical management. Application of disease-modifying therapy likely requires screening of patients with molecular evidence of pathological accumulation and monitoring of treatment effect assisted with biomarkers. There is currently still a gap in specific 4-repeat tau imaging probes for 4-repeat tauopathies and α-synuclein imaging probes for Parkinson’s disease and dementia with Lewy body. In this review, we focused on recent development in molecular imaging biomarkers for assisting the early diagnosis of proteinopathies (i.e., amyloid-β, tau, and α-synuclein) in dementia and discussed future perspectives.

scholarly journals Mineralocorticoid functional of adrenal cortex in patients with pheochromocytoma

2018 ◽  
Vol 10 (1) ◽  
pp. 67-71
Author(s):  
N. V. Vorokhobina ◽  
M. A. Ivanushko ◽  
L. I. Velikanova ◽  
S. B. Shustov ◽  
Z. R. Shafigullina ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Adrenal Cortex ◽  
High Performance ◽  
Renin Angiotensin System ◽  
Gas Chromatography Mass Spectrometry ◽  
Blood Levels ◽  
Urine Excretion ◽  
Angiotensin System ◽  
Positive Correlations ◽  
The Relationship

The article presents the analysis of renin–angiotensin system and content precursor of aldosterone and their metabolites, investigated by methods of high-performance liquid chromatography and gas chromatography – mass-spectrometry in 49 patients with pheochromocytoma (РНЕО) and 28 patients with non-active adenoma of the adrenal cortex and 26 healthy people. In the group of patients with PHEO the increased blood levels оf aldosterone and urine excretion of 18-hydroxycorticosterone, tetrahydrocorticosterone and it 5-α form were obtained. These patients had features of hyporeninemic and hyperreninemic hyperaldosteronism. Positive correlations of urinary excretion of free normetanephrine with blood aldosterone, renin, corticosterone and 18-hydroxycorticosterone suggest the relationship between adrenal cortex and medulla.

scholarly journals Self-Reported Dietary Carotenoid Intake Is Related to Cognitive Outcomes in Early Adolescents

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 124-124
Author(s):  
Cassandra Partridge ◽  
Meredith LaFrance ◽  
Katie Brown ◽  
Benjamin McDunn ◽  
Annie Roe
Keyword(s):  
Working Memory ◽  
Executive Function ◽  
Episodic Memory ◽  
Dietary Intake ◽  
Parent Education ◽  
Processing Speed ◽  
Early Adolescents ◽  
Cognitive Outcomes ◽  
Total Carotenoids ◽  
Dietary Carotenoid

Abstract Objectives To investigate the relationships between self-reported dietary carotenoid intake and cognitive outcomes in adolescents aged 11–14 years. Methods Thirty adolescents aged 11–14 years participated in the cross-sectional study. Dietary intake of lutein and zeaxanthin, lycopene, alpha- and beta-carotene, cryptoxanthin and total carotenoids were assessed from three days of 24-hour dietary recall data collected and analyzed using the Automated Self-Administered 24-hour (ASA24) Dietary Assessment Tool, developed by the National Cancer Institute. Assessments from the NIH Toolbox for Assessment of Neurological and Behavioral Function were administered to determine scores of executive function, episodic memory, working memory, attention, processing speed, and fluid cognition, all adjusted for age, gender, race, ethnicity, and parent education. Spearman correlations were used to evaluate relationships between variable pairs, using SAS software. Results A significant inverse relationship was found between intake of lutein and zeaxanthin and working memory scores (R2 = −0.427, P < 0.05). Significant positive associations were found between scores of episodic memory and intakes of cryptoxanthin (R2 = 0.411, P < 0.05), lycopene (R2 = 0.396, P < 0.05) and total carotenoids (R2 = 0.395, P < 0.05). No significant relationships were noted between intakes of carotenoids and measurements of executive function, attention, processing speed or fluid cognition. Conclusions Dietary intake of lutein and zeaxanthin was negatively associated with working memory scores and intakes of cryptoxanthin, lycopene, and total carotenoids were positively associated with episodic memory scores in early adolescents aged 11–14 years. Dietary intake of specific carotenoids may have varied associations with specific domains of cognition. Larger sample sizes are needed to comprehensively evaluate these relationships in adolescent populations. Funding Sources University of Idaho internal funding.

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