scholarly journals SPON1 Is Associated with Amyloid-β and APOE ε4-Related Cognitive Decline in Cognitively Normal Adults

2021 ◽  
Vol 5 (1) ◽  
pp. 111-120
Author(s):  
Shane Fernandez ◽  
Samantha C. Burnham ◽  
Lidija Milicic ◽  
Greg Savage ◽  
Paul Maruff ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Independent Effect ◽  
Imaging Biomarkers ◽  
Cognitively Normal ◽  
Study Results ◽  
Global Cognition ◽  
Mixed Modelling ◽  
Normal Adults

Abstract. Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer’s disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ɛ4 and rs11023139 in individuals with high amyloid-β burden. APOE ɛ4/rs11023139-A carriers declined significantly faster than APOE ɛ4/rs11023139-G_G carriers in measures of global cognition (p = 0.011) and verbal episodic memory (p = 0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ɛ4 cognitively normal older adults with a high neocortical amyloid-β burden.

scholarly journals Social Engagement and Amyloid-β-Related Cognitive Decline in Cognitively Normal Older Adults

2019 ◽  
Vol 27 (11) ◽  
pp. 1247-1256 ◽  
Author(s):  
Kelsey D. Biddle ◽  
Federico d'Oleire Uquillas ◽  
Heidi I.L. Jacobs ◽  
Benjamin Zide ◽  
Dylan R. Kirn ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Social Engagement ◽  
Amyloid Β ◽  
Cognitively Normal

scholarly journals P3-305: SYNERGISTIC ADVERSE EFFECTS OF WIDOWHOOD AND AMYLOID-β ON COGNITIVE DECLINE IN COGNITIVELY NORMAL OLDER ADULTS

2019 ◽  
Vol 15 ◽  
pp. P1054-P1054
Author(s):  
Kelsey D. Biddle ◽  
Federico d'Oleire Uquillas ◽  
Benjamin Zide ◽  
Dylan Kirn ◽  
Heidi IL. Jacobs ◽  
...  
Keyword(s):  
Older Adults ◽  
Adverse Effects ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Cognitively Normal

scholarly journals Association of cortical microstructure with amyloid-β and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults

2021 ◽  
Author(s):  
Elena Rodriguez-Vieitez ◽  
Victor Montal ◽  
Jorge Sepulcre ◽  
Cristina Lois ◽  
Bernard Hanseeuw ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Structural Changes ◽  
Mean Diffusivity ◽  
Amyloid Β ◽  
Cox Proportional Hazards ◽  
Aging Brain ◽  
Clinical Progression ◽  
Cognitively Normal

AbstractNoninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer’s disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression. The study sample comprised n = 196 cognitively normal older adults (mean[SD] 72.5 [9.4] years; 114 women [58.2%]) from the Harvard Aging Brain Study. At baseline, all participants underwent structural MRI, DWI, 11C-Pittsburgh compound-B-PET, 18F-flortaucipir-PET imaging, and cognitive assessments. Longitudinal measures of Preclinical Alzheimer Cognitive Composite-5 were available for n = 186 individuals over 3.72 (1.96)-year follow-up. Prospective clinical follow-up was available for n = 163 individuals over 3.2 (1.7) years. Surface-based image analysis assessed vertex-wise relationships between cMD, global amyloid-β, and entorhinal and inferior-temporal tau. Multivariable regression, mixed effects models and Cox proportional hazards regression assessed longitudinal cognition, brain structural changes and clinical progression. Tau, but not amyloid-β, was positively associated with cMD in AD-vulnerable regions. Correcting for baseline demographics and cognition, increased cMD predicted steeper cognitive decline, which remained significant after correcting for amyloid-β, thickness, and entorhinal tau; there was a synergistic interaction between cMD and both amyloid-β and tau on cognitive slope. Regional cMD predicted hippocampal atrophy rate, independently from amyloid-β, tau, and thickness. Elevated cMD predicted progression to mild cognitive impairment. Cortical microstructure is a noninvasive biomarker that independently predicts subsequent cognitive decline, neurodegeneration and clinical progression, suggesting utility in clinical trials.

scholarly journals Higher Coffee Consumption Is Associated With Slower Cognitive Decline and Less Cerebral Aβ-Amyloid Accumulation Over 126 Months: Data From the Australian Imaging, Biomarkers, and Lifestyle Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Samantha L. Gardener ◽  
Stephanie R. Rainey-Smith ◽  
Victor L. Villemagne ◽  
Jurgen Fripp ◽  
Vincent Doré ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Protective Factor ◽  
Coffee Consumption ◽  
Imaging Biomarkers ◽  
Coffee Intake ◽  
Cognitively Normal ◽  
Amyloid Accumulation ◽  
Aβ Amyloid ◽  
The Relationship

Background: Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations.Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over 126 months. In a subset of individuals, we also investigated the relationship between habitual coffee intake and cerebral Aβ-amyloid accumulation (n = 60) and brain volumes (n = 51) over 126 months.Results: Higher baseline coffee consumption was associated with slower cognitive decline in executive function, attention, and the AIBL Preclinical AD Cognitive Composite (PACC; shown reliably to measure the first signs of cognitive decline in at-risk cognitively normal populations), and lower likelihood of transitioning to mild cognitive impairment or AD status, over 126 months. Higher baseline coffee consumption was also associated with slower Aβ-amyloid accumulation over 126 months, and lower risk of progressing to “moderate,” “high,” or “very high” Aβ-amyloid burden status over the same time-period. There were no associations between coffee intake and atrophy in total gray matter, white matter, or hippocampal volume.Discussion: Our results further support the hypothesis that coffee intake may be a protective factor against AD, with increased coffee consumption potentially reducing cognitive decline by slowing cerebral Aβ-amyloid accumulation, and thus attenuating the associated neurotoxicity from Aβ-amyloid-mediated oxidative stress and inflammatory processes. Further investigation is required to evaluate whether coffee intake could be incorporated as a modifiable lifestyle factor aimed at delaying AD onset.

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations

2021 ◽  
pp. 1-9
Author(s):  
Gihwan Byeon ◽  
Min Soo Byun ◽  
Dahyun Yi ◽  
Jun Ho Lee ◽  
So Yeon Jeon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Older Adults ◽  
Cognitive Decline ◽  
Brain Atrophy ◽  
Homocysteine Level ◽  
Cognitive Impairments ◽  
Interactive Effect ◽  
Brain Mri ◽  
Amyloid Β ◽  
Serum Homocysteine

Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments. Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI. Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer’s disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD. Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.

scholarly journals Amyloid‐ β , cortical thickness, and subsequent cognitive decline in cognitively normal oldest‐old

2021 ◽  
Vol 8 (2) ◽  
pp. 348-358
Author(s):  
Wiesje Pelkmans ◽  
Nienke Legdeur ◽  
Mara Kate ◽  
Frederik Barkhof ◽  
Maqsood M. Yaqub ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cortical Thickness ◽  
Oldest Old ◽  
Amyloid Β ◽  
Cognitively Normal

scholarly journals The effect of amyloid β on cognitive decline is modulated by neural integrity in cognitively normal elderly

2013 ◽  
Vol 9 (6) ◽  
pp. 687-698.e1 ◽  
Author(s):  
Miranka Wirth ◽  
Hwamee Oh ◽  
Elizabeth C. Mormino ◽  
Candace Markley ◽  
Susan M. Landau ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Amyloid Β ◽  
Cognitively Normal

scholarly journals SAT-LB115 Metformin-Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes Mellitus: The Sydney Memory and Ageing Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Katherine Samaras ◽  
Steve Makkar ◽  
John D Crawford ◽  
Nicole A Kochan ◽  
Wei Wen ◽  
...  
Keyword(s):  
Older Adults ◽  
Heart Disease ◽  
Executive Function ◽  
Older People ◽  
Cognitive Decline ◽  
Community Dwelling ◽  
Incident Dementia ◽  
Ageing Study ◽  
Global Cognition ◽  
Rate Of Decline

Abstract Background Metformin use in diabetes has been associated with both increased and decreased dementia rates in observational studies of people with diabetes. Objective: To examine changes in global cognition and specific cognitive domains over 6 years in older adults with diabetes treated with metformin, compared to other glucose lowering medications, and to people without diabetes. Methods Data were examined from the Sydney Memory and Ageing Study, a prospective observational study of 6 years duration of 1037 non-demented community-dwelling elderly aged 70-90 at baseline, derived from a compulsory electoral roll. Neuropsychological testing was performed every 2 years with domain measures of memory, executive function, language, visuospatial function, attention and processing speed and a composite of global cognition. Data were analysed by linear mixed modelling, including age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking and apolipoprotein E ε4 carriage as covariates. Results: At baseline, 123 participants had diabetes (DM) with 67 receiving metformin (DM+MF) who were similar in demographics to those not receiving metformin (DM-noMF) and those without diabetes (no-DM). Participants with diabetes had higher BMI, lower HDL- and LDL-cholesterol and more prevalent heart disease, hypertension and smoking, compared to no-DM. Over 6-years, DM+MF participants had significantly slower rates of decline in global cognition and executive function, compared to DM-noMF, adjusted for covariates. The rate of decline for each cognitive domain was similar between DM+MF and controls. No impact was found in analyses examining interactions with sex, ApoEε4 carriage or hyperlipidemia. No difference was found in the rate of decline in brain volumes between the groups over 2 years. Incident dementia was significantly higher in DM-noMF, compared to DM+MF (adjusted OR 5.29 [95% CI 1.17-23.88], p,0.05), whereas risk of incident dementia was similar between DM+MF and participants without diabetes. Conclusions: In older people with diabetes receiving metformin, rates of cognitive decline and dementia were similar to that found in people without diabetes and significantly less than that found in people with diabetes not receiving metformin. Large randomized studies in people with and without diabetes are required to determine whether these associations can be attributed to metformin alone or if other factors explain these observations. Future studies will clarify if this cheap and safe medication can be repurposed for prevention of cognitive decline in older people.

Is the Cutoff of the MoCA too High? Longitudinal Data From Highly Educated Older Adults

2019 ◽  
Vol 33 (3) ◽  
pp. 155-160 ◽  
Author(s):  
Odelia Elkana ◽  
Noy Tal ◽  
Noga Oren ◽  
Shani Soffer ◽  
Elissa L. Ash
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Repeated Measures ◽  
Cognitive Assessment ◽  
Digit Span ◽  
Verbal Learning ◽  
Cutoff Score ◽  
Adult Intelligence Scale ◽  
Cognitively Normal ◽  
Highly Educated

Background: The Montreal Cognitive Assessment (MoCA) is widely used to evaluate cognitive decline in older individuals. Although, age and education-related norms have been published, the vast majority of diagnostic clinicians use the MoCA cutoff score to identify patients with cognitive impairment. Aim: To identify whether the MoCA cutoff is too stringent for cognitively normal older adults. Methods: Twenty-seven participants aged 68 to 83 (mean = 75.07, standard deviation [SD] = 4.62), with high education level (mean = 17.14 years, SD = 3.21) underwent cognitive assessment once a year for 5 consecutive years. The cognitive assessment included MoCA; Rey Auditory Verbal Learning Test; Rey Osterrieth Complex Figure test; Wechsler Adult Intelligence Scale Information and Digit Span Subtest; Trail Making Test; Verbal Fluency Test; and Beck Depression Inventory questionnaire. Repeated measures analysis of variance (ANOVA) was used to analyze all standardized scores as well as MoCA standardized and raw scores across all years. Results: Repeated-measures ANOVA for MoCA raw scores yielded significant decline across the years ( P < .05). From the second year and forward, the average MoCA total score was below the cutoff of 26/30. However, in substantial contrast, all other neuropsychological scores and the MoCA standardized scores were within the normal range and even above in all years. Conclusion: Our study demonstrates that the currently used MoCA cutoff is too high even for highly educated, cognitively normal older adults. Therefore, it is crucial to use the age- and education-related norms for the MoCA in order to avoid misdiagnosis of cognitive decline.

scholarly journals Illiteracy, dementia risk, and cognitive trajectories among older adults with low education

Neurology ◽  
2019 ◽  
Vol 93 (24) ◽  
pp. e2247-e2256 ◽  
Author(s):  
Miguel Arce Rentería ◽  
Jet M.J. Vonk ◽  
Gloria Felix ◽  
Justina F. Avila ◽  
Laura B. Zahodne ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Independent Effect ◽  
Growth Curve Models ◽  
Cox Proportional Hazards Models ◽  
Dementia Risk ◽  
Incident Dementia ◽  
Low Education

ObjectiveTo investigate whether illiteracy was associated with greater risk of prevalent and incident dementia and more rapid cognitive decline among older adults with low education.MethodsAnalyses included 983 adults (≥65 years old, ≤4 years of schooling) who participated in a longitudinal community aging study. Literacy was self-reported (“Did you ever learn to read or write?”). Neuropsychological measures of memory, language, and visuospatial abilities were administered at baseline and at follow-ups (median [range] 3.49 years [0–23]). At each visit, functional, cognitive, and medical data were reviewed and a dementia diagnosis was made using standard criteria. Logistic regression and Cox proportional hazards models evaluated the association of literacy with prevalent and incident dementia, respectively, while latent growth curve models evaluated the effect of literacy on cognitive trajectories, adjusting for relevant demographic and medical covariates.ResultsIlliterate participants were almost 3 times as likely to have dementia at baseline compared to literate participants. Among those who did not have dementia at baseline, illiterate participants were twice as likely to develop dementia. While illiterate participants showed worse memory, language, and visuospatial functioning at baseline than literate participants, literacy was not associated with rate of cognitive decline.ConclusionWe found that illiteracy was independently associated with higher risk of prevalent and incident dementia, but not with a more rapid rate of cognitive decline. The independent effect of illiteracy on dementia risk may be through a lower range of cognitive function, which is closer to diagnostic thresholds for dementia than the range of literate participants.

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