scholarly journals Regional hyperperfusion in cognitively normal APOE ε4 allele carriers in mid-life: analysis of ASL pilot data from the PREVENT-Dementia cohort

2020 ◽  
Vol 91 (8) ◽  
pp. 861-866
Author(s):  
Elizabeth Frances McKiernan ◽  
Elijah Mak ◽  
Maria-Eleni Dounavi ◽  
Katie Wells ◽  
Craig Ritchie ◽  
...  
Keyword(s):  
Cerebral Hypoperfusion ◽  
Cognitive Test ◽  
Cognitively Normal ◽  
Apoe Ε4 ◽  
Cerebral Hyperperfusion ◽  
Dementia Risk ◽  
Normal Individuals ◽  
Increased Risk ◽  
Mri Scans ◽  
New Biomarkers

BackgroundRegional cerebral hypoperfusion is characteristic of Alzheimer’s disease (AD). Previous studies report conflicting findings in cognitively normal individuals at high risk of AD. Understanding early preclinical perfusion alterations may improve understanding of AD pathogenesis and lead to new biomarkers and treatment targets.Methods3T arterial spin labelling MRI scans from 162 participants in the PREVENT-Dementia cohort were analysed (cognitively normal participants aged 40–59, stratified by future dementia risk). Cerebral perfusion was compared vertex-wise according to APOE ε4 status and family history (FH). Correlations between individual perfusion, age and cognitive scores (COGNITO battery) were explored.ResultsRegional hyperperfusion was found in APOE ε4+group (left cingulate and lateral frontal and parietal regions p<0.01, threshold-free cluster enhancement, TFCE) and in FH +group (left temporal and parietal regions p<0.01, TFCE). Perfusion did not correlate with cognitive test scores.ConclusionsRegional cerebral hyperperfusion in individuals at increased risk of AD in mid-life may be a very early marker of functional brain change related to AD. Increased perfusion may reflect a functional ‘compensation’ mechanism, offsetting the effects of early neural damage or may itself be risk factor for accelerating spread of degenerative pathology.

scholarly journals Homocysteine levels and dementia risk in Yoruba and African Americans

2013 ◽  
Vol 25 (11) ◽  
pp. 1859-1866 ◽  
Author(s):  
Hugh C. Hendrie ◽  
Olusegun Baiyewu ◽  
Kathleen A. Lane ◽  
Christianna Purnell ◽  
Sujuan Gao ◽  
...  
Keyword(s):  
African Americans ◽  
Vitamin B12 ◽  
Community Dwelling ◽  
Performance Category ◽  
Cognitively Normal ◽  
Significant Relationships ◽  
Dementia Risk ◽  
Incident Dementia ◽  
Increased Risk

ABSTRACTBackground:High levels of homocysteine have been associated with increased risk for dementia although results have been inconsistent. There are no reported studies from the developing world including Africa.Methods:In this longitudinal study of two community-dwelling cohorts of elderly Yoruba and African Americans, levels of homocysteine, vitamin B12 and folate were measured from blood samples taken in 2001. These levels were compared in two groups, participants who developed incident dementia in the follow-up until 2009 (59 Yoruba and 101 African Americans) and participants who were diagnosed as cognitively normal or in the good performance category at their last follow-up (760 Yoruba and 811 African Americans). Homocysteine levels were divided into quartiles for each site.Results:After adjusting for age, education, possession of ApoE, smoking, and time of enrollment the higher quartiles of homocysteine were associated with a non-significant increase in dementia risk in the Yoruba (homocysteine quartile 4 vs. 1 OR: 2.19, 95% CI 0.95–5.07, p = 0.066). For the African Americans, there was a similar but non-significant relationship between higher homocysteine levels and dementia risk. There were no significant relationships between levels of vitamin B12 and folate and incident dementia in either site although folate levels were lower and vitamin B12 levers were higher in the Yoruba than in the African Americans.Conclusions:Increased homocysteine levels were associated with a similar but non-significant increase in dementia risk for both Yoruba and African Americans despite significant differences in folate levels between the two sites.

scholarly journals Impaired Odor Identification of Culturally Familiar Odorants Associated with Dementia in South Korean Older Adults

2020 ◽  
Vol 17 (22) ◽  
pp. 8441
Author(s):  
Sun Mi Kim ◽  
Hye Ri Kim ◽  
Hyun Jin Min ◽  
Kyung Soo Kim ◽  
Hyuk Ga ◽  
...  
Keyword(s):  
Older Adults ◽  
Odor Identification ◽  
Cognitively Normal ◽  
South Korean ◽  
Hierarchical Logistic Regression ◽  
Dementia Risk ◽  
Normal Individuals ◽  
Diagnosis Of Dementia ◽  
Identification Function ◽  
Normal Cognition

Among olfactory functions, odor identification is the most studied predictor of dementia. We aimed to verify whether patients with dementia are less aware of specific odors than cognitively normal individuals using an odor identification test, which includes odorants that are culturally familiar to South Koreans. We divided 139 older adults aged 57–79 years into the dementia and normal cognition groups. Odor identification function was assessed in all participants. We conducted hierarchical logistic regression analyses with the diagnosis of dementia as a dependent variable and three demographic characteristics, as well as 12 odor identification items, as independent variables. Impaired odor identification for herbal medicine (odds ratio (OR) = 9.420; p = 0.012) and Korean grilled meat (OR = 5.361; p = 0.019) and older age (OR = 1.176; p = 0.005) were significant predictors of dementia. Impaired odor identification of culturally familiar odorants was associated with dementia risk. This may be explained by the fact that compared with culturally non-specific universal odorants, familiar odorants are more related to episodic memory, which is impaired in the early stages of dementia. Thus, an optimal combination of odor identification items should be used for screening individuals with cognitive decline requiring further neurocognitive function tests.

scholarly journals Predictors of Incident Mild Cognitive Impairment and Its Course in a Diverse Community-Based Population

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013017
Author(s):  
Milou J Angevaare ◽  
Jet M.J. Vonk ◽  
Laiss Bertola ◽  
Laura Zahodne ◽  
Caitlin Wei-Ming Watson ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Leisure Activities ◽  
Community Based ◽  
Cognitively Normal ◽  
Clinical Criteria ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Antidepressant Use

Objective:To investigate socio-demographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia.Methods:Within a community-based cohort, diagnoses of MCI were made using a published algorithm. Diagnosis of dementia was based on clinical consensus. Cox regressions estimated hazard ratios of incident MCI associated with several predictors. Modified Poisson regressions estimated relative risks associated with predictors of diagnostic status at follow-up after incidence.Results:Among 2903 cognitively normal participants at baseline, 752 developed MCI over an average of 6.3 (SD=4.5) years (incidence rate: 56/1,000 person-years). Presence of APOE ε4 and higher medical burden increased risk of incident MCI, while more years of education, more leisure activities, and higher income decreased this risk. Of the incident MCI cases, after an average of 2.4 years follow-up, 12.9% progressed to dementia, 9.6% declined in functioning and did not meet the algorithmic criteria for MCI but did not meet the clinical criteria for dementia either, 29.6% continued to meet MCI criteria, and 47.9% no longer met MCI criteria. Multi-domain MCI, presence of APOE ε4, depressive symptoms and antidepressant use increased the risk of progression to dementia.Conclusions:This community-based study showed that almost half of the individuals with incident MCI diagnoses were classified as cognitively normal at follow-up. Predictors of incident MCI demonstrably differed from those of subsequent MCI course; these findings can refine expectations for cognitive and functional course of those presenting with MCI.

Association of Subjective Cognitive Decline with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study

2021 ◽  
pp. 1-9
Author(s):  
Chen Wen ◽  
Yan-Lin Bi ◽  
Hao Hu ◽  
Shu-Yi Huang ◽  
Ya-Hui Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Csf Biomarkers ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Increased Risk ◽  
T Tau

Background: Subjective cognitive decline (SCD) might occur at the early stages of dementia. Individuals with SCD have an increased risk of subsequent objective cognitive decline and greater rates of progression to dementia. Objective: We aimed to explore the associations between SCD and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in cognitively normal individuals. Methods: A total of 1,099 cognitively normal elders with available data on CSF biomarkers of AD pathology (Aβ 42, P-tau, and T-tau) were included in our analysis. Linear regression was used to examine the associations of SCD status and SCD severity with CSF biomarkers. Additionally, a review was conducted to discuss the associations between SCD and CSF biomarkers of AD pathology. Results: After adjustments for covariates, SCD and SCD severity showed significant associations with CSF Aβ 42 (SCD: β= –0.0003, p = 0.0263; SCD severity: β= –0.0004, p = 0.0046), CSF T-tau/Aβ 42 ratio (SCD: β= 0.1080, p = 0.1080; SCD severity: β= 0.1129, p = 0.0009) and CSF P-tau/Aβ 42 ratio (SCD: β= 0.0167, p = 0.0103; SCD severity: β= 0.0193, p = 0.0006) rather than T-tau and P-tau compared with cognitively normal individuals. In the review, a total of 28 studies were finally included after reviewing 174 articles. CSF Aβ 42 was lower in SCD than cognitively normal (CN) individuals, but higher than those with objective cognitive decline. However, CSF tau pathology showed no difference between SCD and CN. Conclusion: The results indicated that pathophysiological changes in CSF Aβ pathology occurred in individuals with SCD, which provide new insights into early intervention of AD.

scholarly journals APOE ε4 Carriers Have a Greater Propensity to Glycation and sRAGE Which Is Further Influenced by RAGE G82S Polymorphism

2019 ◽  
Vol 75 (10) ◽  
pp. 1899-1905 ◽  
Author(s):  
Permal Deo ◽  
Varinderpal S Dhillon ◽  
Ann Chua ◽  
Philip Thomas ◽  
Michael Fenech
Keyword(s):  
Plasma Cholesterol ◽  
High Plasma ◽  
Advanced Glycation ◽  
Cognitively Normal ◽  
Apoe Ε4 ◽  
Established Risk Factor ◽  
Normal Individuals ◽  
Glycation End Products ◽  
Ε4 Allele ◽  
The Common

Abstract APOE ε4 allele is an established risk factor for Alzheimer’s disease and hypercholesterolemia. However, its association with metabolic and genetic risk factors related to glycation is not clear. We tested the hypothesis that, apart from high plasma cholesterol, APOE ε4 carriers may also have higher advanced glycation end products (AGEs) and total soluble extracellular domain of RAGE (sRAGE) and that these biomarkers may be modified by the common Gly82Ser (G82S) polymorphism (rs2070600) in the RAGE gene. To test this, we measured these biomarkers in 172 healthy cognitively normal individuals, of which 32 were APOE ε4 carriers and 140 noncarriers. APOE ε4 carriers showed higher levels of cholesterol (p &lt; .001), glyoxal (p &lt; .001), fluorescent AGEs (p &lt; .001), Nε-carboxymethyllysine (p &lt; .001) and sRAGE (p = .018) when compared to noncarriers. Furthermore, sRAGE was also higher in those that did not carry the A allele of the RAGE gene that codes for serine instead of glycine (p = .034). Our study indicates that APOE ε4 carriers have a greater propensity to glycation than noncarriers which may further increase their risk for diabetes and dementia. The increased sRAGE levels in APOE ε4 carriers suggests a defensive response against AGEs that may be further influenced by the RAGE G82S polymorphism.

Abstract MP05: Mid-Life Vitamin D Levels are Not Associated with Cognition and Dementia Risk in Whites and Blacks: the Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Andrea L Schneider ◽  
Pamela L Lutsey ◽  
Alvaro Alonso ◽  
Rebecca F Gottesman ◽  
A R Sharrett ◽  
...  
Keyword(s):  
Vitamin D ◽  
Test Scores ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Word Recall ◽  
Cognitive Test ◽  
Cross Sectional ◽  
Dementia Risk ◽  
Increased Risk ◽  
Vitamin D Levels

Introduction: Recent studies, mainly performed in elderly whites, suggest that vitamin D, measured by 25-hydroxyvitamin D [25(OH)D], is important for cognition. Less is known about the association of 25(OH)D measured in mid-life with cognition and dementia risk in whites and blacks. Hypothesis: We hypothesized that lower concentrations of 25(OH)D would be associated cross-sectionally with lower cognitive test scores and prospectively with greater decline in cognitive test scores and with increased risk of dementia. Methods: We conducted cross-sectional (1993-1995), change (1993-1995 to 2004-2006), and prospective (follow-up through 2010) analyses of 1,652 participants in the ARIC Brain Ancillary Study with measured 25(OH)D (1993-1995). 25(OH)D was analyzed in race-specific tertiles and continuously. Cognition was measured by 3 tests: Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF). Dementia was defined by hospitalization ICD-9 codes. Adjusted race-stratified linear regression and Cox proportional hazards models were used. Results: Mean age of participants was 62 years, 60% were female, and 48% were black. Mean 25(OH)D was higher in whites than blacks (25.5 versus 17.3 ng/ml, p<0.05). Over a median of 16.6 years, there were 145 incident hospitalized dementia cases. In prospective analyses, lower levels of 25(OH)D trended towards an association with increased dementia risk in whites and in blacks, but these results were not statistically significant (lowest versus highest tertile: whites, HR: 1.32 [95% CI: 0.69, 2.55]; blacks, HR: 1.53 [95% CI: 0.84, 2.79]) (Figure). Conclusion: In contrast to prior studies performed in elderly populations, our study did not find significant associations between lower levels of 25(OH)D in mid-life with lower cognitive test scores at baseline, change in score over time, or increased dementia risk.

scholarly journals Intradialytic Cerebral Hypoperfusion as Mechanism for Cognitive Impairment in Patients on Hemodialysis

2019 ◽  
Vol 30 (11) ◽  
pp. 2052-2058 ◽  
Author(s):  
Dawn F. Wolfgram
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Perfusion ◽  
Ischemic Injury ◽  
Hemodialysis Patients ◽  
Cognitive Outcomes ◽  
Cerebral Injury ◽  
Cerebral Hypoperfusion ◽  
Increased Risk ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

The high frequency of cognitive impairment in individuals on hemodialysis is well characterized. In-center hemodialysis patients are disproportionately affected by cognitive impairment compared with other dialysis populations, identifying hemodialysis itself as a possible factor. The pathophysiology of cognitive impairment has multiple components, but vascular-mediated cerebral injury appears to contribute based on studies demonstrating increased cerebral ischemic lesions and atrophy in brain imaging of patients on hemodialysis. Patients on hemodialysis may be at increased risk for cerebral ischemic injury disease due to vasculopathy associated with ESKD and from their comorbid diseases, such as hypertension and diabetes. This review focuses on the intradialytic cerebral hypoperfusion that can occur during routine hemodialysis due to the circulatory stress of hemodialysis. This includes a review of current methods used to monitor intradialytic cerebral perfusion and the structural and functional cognitive outcomes that have been associated with changes in intradialytic cerebral perfusion. Monitoring of intradialytic cerebral perfusion may become clinically relevant as nephrologists try to avoid the cognitive complications seen with hemodialysis. Identifying the appropriate methods to assess risk for cerebral ischemic injury and the relationship of intradialytic cerebral hypoperfusion to cognitive outcomes will help inform the decision to use intradialytic cerebral perfusion monitoring in the clinical setting as part of a strategy to prevent cognitive decline.

scholarly journals Lower functional hippocampal redundancy in mild cognitive impairment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie Langella ◽  
◽  
Muhammad Usman Sadiq ◽  
Peter J. Mucha ◽  
Kelly S. Giovanello ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Resting State ◽  
Memory Performance ◽  
Potential Mechanism ◽  
Network Efficiency ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
The Relationship

AbstractWith an increasing prevalence of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in response to an aging population, it is critical to identify and understand neuroprotective mechanisms against cognitive decline. One potential mechanism is redundancy: the existence of duplicate elements within a system that provide alternative functionality in case of failure. As the hippocampus is one of the earliest sites affected by AD pathology, we hypothesized that functional hippocampal redundancy is protective against cognitive decline. We compared hippocampal functional redundancy derived from resting-state functional MRI networks in cognitively normal older adults, with individuals with early and late MCI, as well as the relationship between redundancy and cognition. Posterior hippocampal redundancy was reduced between cognitively normal and MCI groups, plateauing across early and late MCI. Higher hippocampal redundancy was related to better memory performance only for cognitively normal individuals. Critically, functional hippocampal redundancy did not come at the expense of network efficiency. Our results provide support that hippocampal redundancy protects against cognitive decline in aging.

scholarly journals Cognitive impact of COVID-19: looking beyond the short term

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Scott Miners ◽  
Patrick G. Kehoe ◽  
Seth Love
Keyword(s):  
Endothelial Cells ◽  
Immune Activation ◽  
Angiotensin Receptor Blockers ◽  
Amyloid Β ◽  
Neurological Complications ◽  
Cerebral Hypoperfusion ◽  
Cerebral White Matter ◽  
Ischaemic Damage ◽  
Hospitalised Patients ◽  
Increased Risk

AbstractCOVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-19 are likely to impact on cognition. Cerebral white matter is particularly vulnerable to ischaemic damage in COVID-19 and is also critically important for cognitive function. There is accumulating evidence that cerebral hypoperfusion accelerates amyloid-β (Aβ) accumulation and is linked to tau and TDP-43 pathology, and by inducing phosphorylation of α-synuclein at serine-129, ischaemia may also increase the risk of development of Lewy body disease. Current therapies for COVID-19 are understandably focused on supporting respiratory function, preventing thrombosis and reducing immune activation. Since angiotensin-converting enzyme (ACE)-2 is a receptor for SARS-CoV-2, and ACE inhibitors and angiotensin receptor blockers are predicted to increase ACE-2 expression, it was initially feared that their use might exacerbate COVID-19. Recent meta-analyses have instead suggested that these medications are protective. This is perhaps because SARS-CoV-2 entry may deplete ACE-2, tipping the balance towards angiotensin II-ACE-1-mediated classical RAS activation: exacerbating hypoperfusion and promoting inflammation. It may be relevant that APOE ε4 individuals, who seem to be at increased risk of COVID-19, also have lowest ACE-2 activity. COVID-19 is likely to leave an unexpected legacy of long-term neurological complications in a significant number of survivors. Cognitive follow-up of COVID-19 patients will be important, especially in patients who develop cerebrovascular and neurological complications during the acute illness.

scholarly journals Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults

2021 ◽  
Vol 11 (1) ◽  
pp. 68
Author(s):  
Sara G. Aguilar-Navarro ◽  
Itzel I. Gonzalez-Aparicio ◽  
José Alberto Avila-Funes ◽  
Teresa Juárez-Cedillo ◽  
Teresa Tusié-Luna ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Cognitive Impairment ◽  
Cardiovascular Risk ◽  
Mild Cognitive Impairment ◽  
Cardiovascular Risk Factors ◽  
Apoe Genotype ◽  
Carrier Status ◽  
Apoe Ε4 ◽  
Increased Risk

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

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