scholarly journals Metabolic syndrome is associated with poor cognition: a population-based study of 70-year-olds without dementia

2021 ◽  
Author(s):  
Anna Marseglia ◽  
Alexander Darin-Mattsson ◽  
Johan Skoog ◽  
Lina Rydén ◽  
Timothy Hadarsson-Bodin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Heart Disease ◽  
Executive Function ◽  
Cognitive Performance ◽  
Birth Cohort ◽  
Verbal Fluency ◽  
Apoe Genotype ◽  
Perceptual Speed ◽  
Apoe Ε4 ◽  
Ε4 Allele

Abstract Background Individual conditions of metabolic syndrome (MetS) have been related to dementia, however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors. Methods Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least two factors [reduced HDL-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from ten neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein (APOE) genotype were ascertained by trained staff. Data were analyzed with linear regression models. Results Overall, 618 participants (55%) had MetS. In multi-adjusted linear regressions, MetS was related to poorer performance in attention/perceptual speed (β -0.14 [95% CI -0.25, -0.02]), executive function (β -0.12 [95% CI -0.23, -0.01]), and verbal fluency (β -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-ε4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone. Conclusions MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, APOE-ε4 allele, and comorbid cardiovascular disease influenced the observed associations.

Cognitive asymmetries associated with apolipoprotein E genotype in patients with Alzheimer's disease

2003 ◽  
Vol 9 (5) ◽  
pp. 751-759 ◽  
Author(s):  
MICHAEL J. FINTON ◽  
JOHN A. LUCAS ◽  
JULIE D. RIPPETH ◽  
DARYL L. BOHAC ◽  
GLENN E. SMITH ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Cognitive Performance ◽  
Cognitive Abilities ◽  
Apoe Genotype ◽  
Unique Contribution ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
The Relationship

The relationship between apolipoprotein E (apoE) genotype and cognitive performance was examined in 200 patients with probable Alzheimer's disease (AD). Differences between composite measures of verbal and nonverbal functioning were used to define asymmetric patterns of cognition. Patients who were homozygous for apoE ε4 demonstrated relatively worse nonverbal as compared to verbal cognitive ability. In contrast, participants who were heterozygous for apoE ε4 or who possessed no ε4 allele demonstrated relatively equivalent verbal and nonverbal cognitive abilities. Although age and dementia severity also contributed to these patterns, apoE genotype appears to have a significant unique contribution to cognitive performance in these individuals. The ε4 allele may thus be associated with a specific neurocognitive phenotype among patients with AD, with the overall pattern of cognitive asymmetry dependent upon ε4 dose. (JINS, 2003, 9, 751–759.)

scholarly journals Decline in verbal memory during preclinical Alzheimer's disease: Examination of the effect of APOE genotype

2002 ◽  
Vol 8 (7) ◽  
pp. 943-955 ◽  
Author(s):  
KELLY L. LANGE ◽  
MARK W. BONDI ◽  
DAVID P. SALMON ◽  
DOUGLAS GALASKO ◽  
DEAN C. DELIS ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Episodic Memory ◽  
Verbal Memory ◽  
Verbal Learning ◽  
Apoe Genotype ◽  
Apoe Ε4 ◽  
Dementia Syndrome ◽  
Ε4 Allele

A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-ε4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE ε4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale–Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-ε4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD. (JINS, 2002, 8, 943–955.)

Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease

2018 ◽  
Vol 15 (10) ◽  
pp. 938-950 ◽  
Author(s):  
Martina Zverova ◽  
Eva Kitzlerova ◽  
Zdenek Fisar ◽  
Roman Jirak ◽  
Jana Hroudova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Apoe Genotype ◽  
Plasma Biomarkers ◽  
Plasma Melatonin ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Severity Of Dementia

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. Objective: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. Method: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. Results: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. Conclusion: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.

scholarly journals Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study

2019 ◽  
Vol 188 (12) ◽  
pp. 2175-2187 ◽  
Author(s):  
Nicole M Armstrong ◽  
Katherine J Bangen ◽  
Rhoda Au ◽  
Alden L Gross
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Executive Function ◽  
Cognitive Performance ◽  
Late Life ◽  
Later Life ◽  
Cognitive Change ◽  
Carrier Status ◽  
Allele Carrier ◽  
Chd Risk

Abstract It is unclear how coronary heart disease (CHD) risk across the adult life span affects late-life cognition. We estimated associations of midlife and late-life elevated CHD risk with cognitive trajectories (general cognitive performance, processing speed/executive function, memory) in later life (after age 55 years or age 70 years) among 2,892 Framingham Offspring Study participants who had completed CHD risk assessments approximately every 4 years since 1971 and had undergone neuropsychological testing between 1999 and 2014. We stratified analyses by apolipoprotein E gene (APOE) Ɛ4 allele carrier status. Using linear mixed-effects models, elevated CHD risk in midlife (age 55 years) was associated with lower levels of general cognitive performance (β = −0.560 standard deviation (SD) units, 95% confidence interval (CI): −0.874, −0.246), executive function (β = −0.624 SD units, 95% CI: −0.916, −0.332), and memory (β = −0.560 SD units, 95% CI: −0.907, −0.213) at age 70 years but not with rates of cognitive change. Late-life (age 70 years) elevated CHD risk, however, was associated with somewhat better levels of general cognitive performance and memory. There were associations between duration of elevated CHD risk during midlife and levels (but not trajectories) of later-life cognitive outcomes. Associations were not modified by APOE-ɛ4 status. These findings suggest that midlife elevated CHD risk is associated with lower cognition, independently of APOE-ɛ4 status, suggesting that risk of vascular disease may not contribute a “second hit” to AD risk.

scholarly journals Low Serum Choline Concentrations Are Associated with Worse Cognitive Performance in Subjects with Metabolic Syndrome

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1200-1200
Author(s):  
Oscar Coltell ◽  
Eva M Asensio ◽  
Jose V Sorlí ◽  
Rebeca Fernández-Carrión ◽  
José I Giménez-Alba ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cognitive Performance ◽  
Verbal Fluency ◽  
Multivariate Model ◽  
Neuroprotective Effects ◽  
Funding Sources ◽  
Type 2 Diabetics ◽  
Phonemic Fluency ◽  
Trail Making ◽  
Essential Nutrient

Abstract Objectives Choline is an essential nutrient critical for components of the cell membrane, such as choline-containing phospholipids (phosphatidylcholine and sphingomyelin), and in synthesis of the neurotransmitter acetylcholine. Choline has been shown to exert neuroprotective effects, but the association between serum choline and cognitive performance has been scarcely investigated. Our aims are: 1) To study the association between serum total choline, phosphatidylcholine and sphingomyelin with cognitive performance in subjects with metabolic syndrome; and 2) to analyze genetic variants and dietary intake most associated with cholines in this population. Methods We analyzed 426 subjects (aged 55–75 y) with metabolic syndrome from the PREDIMED Plus-Valencia Study. Serum total choline, phosphatidylcholine and sphingomyelin were determined by NMR spectroscopy. Cognitive tests, including verbal fluency (both semantic and phonemic fluency) and the Trail Making Test (TMT) (parts A and B), were administered. Candidate gene polymorphisms were determined by array genotyping. Diet was analyzed by validated questionnaires. Multivariate regression models were fitted. Results Cholines (total, phosphatidylcholine and sphingomyelin) were strongly associated with sex (higher in women; P < 0.001), age (lower at increasing age; P < 0.05) and diabetes (lower in type-2 diabetics; P < 0.01) in a multivariate model. Although the three tested variables presented statistically significant associations with cognition, serum sphingomyelin was the most associated. Thus, in a multivariate model, serum phosphatidylcholine was directly associated with better verbal fluency (P = 0.040 and P = 0.029 for phonemic and semantic, respectively) and inversely associated (lower score mean better performance) with the TMT-A (P = 0.013) and the TMT-B (P = 0.035). In the genetic analysis, we detected several polymorphisms strongly associated with cholines (rs10991629-SLC44A1 with P < 0.005 and rs8068641-PEMT; P < 0.01, among others). We identified several dietary associations as well as gene-diet modulations. Conclusions Phosphatidylcholines are associated with better cognitive function and their levels are modulated by diet and genetics. Funding Sources Generalitat Valenciana (PROMETEO2017/017) and Spanish Ministry of Science (FPU 18/0,1703).

Abstract P67: Role of Genetic Variants in Predicting Cognitive Outcomes Following Small Vessel Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Wayneho Kam ◽  
Larry B Goldstein ◽  
Alec McConnell ◽  
Hussein Al-Khalidi ◽  
Ellen Bennett ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Executive Function ◽  
Cognitive Assessment ◽  
Cognitive Outcomes ◽  
Small Vessel ◽  
Nihss Score ◽  
Post Stroke ◽  
Apoe Ε4 ◽  
Ε4 Allele

Background: About 20% of patients with small vessel ischemic stroke (SVS) have cognitive impairment; however, the role of genetic factors in predicting cognitive outcomes following SVS has not been fully explored. APOE and ABCC9 have been associated with Alzheimer’s disease and hippocampal sclerosis respectively and play an important role in the neurovascular unit. We evaluated whether allelic variants in these genes influence cognitive outcomes following SVS. Methods: We conducted a retrospective analysis of a prospective cohort of patients enrolled in the ASA-Bugher Small Vessel Intracranial Disease Whole Genome Association Studies. Patients with SVS were categorized by APOE (presence or absence of ε4 allele) and ABCC9 SNP rs704180 (presence or absence of A allele) status. The primary outcomes were total score on the short form of the MoCA, which assesses global cognition, and time to complete Trails B, which is a measure of executive function that can be affected by stroke. Linear regression analyses were performed using the genetic exposures of interest, adjusting for age, education, sex, race/ethnicity, NIHSS score, burden of white matter disease (WMD; using the CHS validated score 0-9), and time between stroke and the cognitive assessment. Results: The sample included 145 patients who had SVS and available APOE and ABCC9 data. Among this cohort, 51.4% were men and 27.6% African American. The median age of the study participants was 63.4 years, the median years of education was 12, the median NIHSS was 2, and the median WMD burden score was 2. The mean time between stroke and the cognitive assessment was 75 days. The APOE ε4 allele was present in 35.0% and ABCC9 A allele in 74.8%. The presence of APOE ε4 allele was not associated with post-stroke MoCA scores (p=0.31) or Trails B (p=0.86). ABCC9 A allele was also not associated with post-stroke MoCA scores (p=0.34) or Trails B (p=0.31). Older age, higher NIHSS score, and greater burden of WMD were independently associated with longer times to complete Trails B (p<0.0001), but not with the MoCA score. Conclusion: Following SVS, several patient characteristics, including age, stroke severity, and WMD burden, rather than their APOE and ABCC9 allelic statuses, were associated with post-stroke measures of executive function.

scholarly journals Presence of the APOE ε4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine–Syracuse Study

Diabetologia ◽  
2009 ◽  
Vol 52 (12) ◽  
pp. 2551-2560 ◽  
Author(s):  
G. A. Dore ◽  
M. F. Elias ◽  
M. A. Robbins ◽  
P. K. Elias ◽  
Z. Nagy
Keyword(s):  
Type 2 Diabetes ◽  
Cognitive Performance ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
The Relationship

Does Apolipoprotein E Influence Learning and Memory in the Nondemented Oldest Old?

2001 ◽  
Vol 13 (4) ◽  
pp. 451-459 ◽  
Author(s):  
Anne Salo ◽  
Raija Ylikoski ◽  
Auli Verkkoniemi ◽  
Tuomo Polvikoski ◽  
Kati Juva ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Learning And Memory ◽  
Verbal Fluency ◽  
Oldest Old ◽  
Very Elderly ◽  
Object Memory ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Relationship Of ◽  
The Relationship

The objective of this study was to analyze the relationship of the apolipoprotein E (apoE) ε4 and ε2 alleles to learning and memory performances in the nondemented oldest old. Forty-six nondemented persons aged 85 years or over from a randomly selected group of 128 subjects in Vantaa, Finland, were studied. ApoE genotyping was performed using the minisequencing technique. A structured clinical examination and interview were carried out. The test variables studied were learning and memory scores (from the Fuld Object-Memory Evaluation), verbal fluency, and conceptualization (the Similarities subtest of the WAIS-R). We compared apoE-ε4 carriers to noncarriers and apoE-ε2 carriers to noncarrirs. No statistically significant differences were found in any of the test variables. The results failed to confirm the hypotheses that poor cognitive performance is associated with the apoE-ε4 allele and good performance with the apoE-ε2 allele in the oldest old. This suggests that the apoE alleles do not have a detectable relationship to learning and memory in nondemented very elderly people.

scholarly journals APOE ε4 allele advances the age-dependent decline of amyloid β clearance in the human cortex

2021 ◽  
Author(s):  
Atsushi Saito ◽  
Yusuke Kageyama ◽  
Olga Pletnikova ◽  
Gay L Rudow ◽  
Yang An ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Apoe Genotype ◽  
Amyloid Β ◽  
Clinical Intervention ◽  
Immunohistochemical Localization ◽  
Human Cortex ◽  
Apoe Ε4 ◽  
Age Related ◽  
Age Dependent ◽  
Ε4 Allele

Introduction: Our previous study indicated that the pericapillary clearance of amyloid β (Aβ) declines with age in APOE 3/3 subjects. Here, we examine whether the APOE ε4 allele has an impact on this age-related decline. Methods: We examined 69 autopsy brains of APOE ε3/ε4 or APOE ε3/ε3 individuals (30-65 years) for the immunohistochemical localization of intracellular, extracellular, and pericapillary Aβ in the cerebral cortex. Results: In APOE ε3/ε4 individuals, the percentage of Aβ positive pericapillary spaces began to decrease (p=0.030), and the number of extracellular Aβ particles increased in the early 30s (p=0.0008). Those average values were significantly lower (p<0.0001) and higher (p<0.0001), respectively, compared to APOE ε3/ε3 individuals. Discussion: Our observations indicate that APOE ε4 allele advances by one decade at the onset of age-related decline in Aβ glymphatic clearance. This finding supports early clinical intervention and stratification by APOE genotype to prevent Aβ deposition and AD progression.

scholarly journals The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype

2020 ◽  
Vol 17 (7) ◽  
pp. 667-679
Author(s):  
Matteo De Marco ◽  
Riccardo Manca ◽  
Janine Kirby ◽  
Guillaume M. Hautbergue ◽  
Daniel J. Blackburn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Functioning ◽  
Grey Matter ◽  
Linear Models ◽  
Apoe Genotype ◽  
Apoe Ε4 ◽  
Allele Status ◽  
Ε4 Allele ◽  
Clinical Profiles

Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles. Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers. Methods: A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps. Results: PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants. Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.

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