Lack of association between proton pump inhibitor use and brain aging: a cross-sectional study

Abstract Purpose Due to conflicting scientific evidence for an increased risk of dementia by intake of proton pump inhibitors (PPIs), this study investigates associations between PPI use and brain volumes, estimated brain age, and cognitive function in the general population. Methods Two surveys of the population-based Study of Health in Pomerania (SHIP) conducted in Northeast Germany were used. In total, 2653 participants underwent brain magnetic resonance imaging (MRI) and were included in the primary analysis. They were divided into two groups according to their PPI intake and compared with regard to their brain volumes (gray matter, white matter, total brain, and hippocampus) and estimated brain age. Multiple regression was used to adjust for confounding factors. Cognitive function was evaluated by the Verbal Learning and Memory Test (VLMT) and the Nuremberg Age Inventory (NAI) and put in relation to PPI use. Results No association was found between PPI use and brain volumes or the estimated brain age. The VLMT score was 1.11 lower (95% confidence interval: − 2.06 to − 0.16) in immediate recall, and 0.72 lower (95% CI: − 1.22 to − 0.22) in delayed recall in PPI users than in non-users. PPI use was unrelated to the NAI score. Conclusions The present study does not support a relationship between PPI use and brain aging.

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Elevated Serum Uric Acid Levels Are Related to Cognitive Deterioration in an Elderly Japanese Population

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000454660 ◽

2016 ◽

Vol 6 (3) ◽

pp. 580-588 ◽

Cited By ~ 1

Author(s):

Kazushi Suzuki ◽

Daisuke Koide ◽

Kurumi Fujii ◽

Tsutomu Yamazaki ◽

Shoji Tsuji ◽

...

Keyword(s):

Uric Acid ◽

Cognitive Function ◽

Serum Uric Acid ◽

Elevated Serum ◽

Brain Magnetic Resonance Imaging ◽

Vascular Pathology ◽

Cognitive Deterioration ◽

Imaging Data ◽

Cross Sectional ◽

Increased Risk

Aims: The association between serum uric acid (UA) levels and cognitive function is controversial since UA can be a risk factor for cerebral ischemia as well as acting as a neuroprotective antioxidant. Methods: We conducted a cross-sectional analysis of 228 elderly participants and examined neuropsychological test results, clinical data as well as brain magnetic resonance imaging data. Patients: Overall, 64 participants were diagnosed with cognitive deterioration. To control for the effect of sex differences, 2 independent sets of single-variable and multivariate logistic regression analyses were performed with quartiles divided into non-sex-specific and sex-specific cutoff values for UA. Results: In non-sex-specific quartiles, the participants in the highest quartiles of UA levels were found to be at a significantly higher risk of cognitive deterioration than those in the lowest quartiles. In sex-specific quartiles, the highest quartile showed an increased risk of cognitive deterioration, and a greater than fourfold increase in the risk in the highest quartiles was confirmed using multivariate regression models. However, no significant association was observed between serum UA levels and the presence of white matter lesions. Conclusions: Elevated serum UA levels were independently associated with cognitive deterioration. UA might have unknown adverse effects on cognitive function, other than causing vascular pathology.

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Long-term anabolic androgenic steroid use is associated with deviant brain aging

10.1101/2020.08.19.20177832 ◽

2020 ◽

Author(s):

Astrid Bjørnebekk ◽

Tobias Kaufmann ◽

Lisa E. Hauger ◽

Sandra Klonteig ◽

Ingunn R. Hullstein ◽

...

Keyword(s):

Cognitive Abilities ◽

Brain Aging ◽

Group Differences ◽

High Dose ◽

Cross Sectional ◽

Brain Volumes ◽

History Of ◽

History Of Use ◽

Brain Age

AbstractBackgroundHigh-dose long-term use of anabolic-androgenic steroids (AAS) may bring a range of health consequences, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging.MethodsT1-weighted MRI (3D MPRAGE) scans were obtained from male weightlifters with a history of prolonged (n=130) or no (n=99) AAS use. We trained machine learning models on combinations of regional brain volumes, cortical thickness and surface area in an independent training set of 1838 healthy males (18-92 years) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval 3.5 years, n=76) MRI data, we used linear mixed effects (LME) models to compare the gap between chronological age and predicted brain age (the brain age gap, BAG) between the two groups, and tested for group differences in the change rate of BAG. We tested for associations between apparent brain aging and AAS use duration, administration pattern and dependence.ResultsAAS users had higher BAG compared to weightlifting controls, associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities or depression. Longitudinal data revealed no evidence of accelerated brain aging in the overall AAS group, though accelerated brain aging was seen with longer AAS exposure.ConclusionsThe findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AAS.

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Association of Circulating Cholesterol Level with Cognitive Function and Mild Cognitive Impairment in the Elderly: A Community-based Population Study

Current Alzheimer Research ◽

10.2174/1567205017666200810165758 ◽

2020 ◽

Vol 17 (6) ◽

pp. 556-565

Author(s):

Yujie Guo ◽

Pengfei Li ◽

Xiaojun Ma ◽

Xiaochen Huang ◽

Zhuoheng Liu ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

Cholesterol Level ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Cross Sectional ◽

Increased Risk ◽

Aging Adults ◽

Female Subjects

Background: The present study was designed to examine the association of circulating cholesterol with cognitive function in non-demented community aging adults. Methods: This was a cross-sectional study including 1754 Chinese adults aged 55-80 years. The association between serum cholesterol levels and cognitive function was examined. Participants were categorized into four groups according to the quartile of circulating TC (total cholesterol), High Density Lipoprotein Cholesterol (HDL-c), Low Density Lipoprotein Cholesterol (LDL-c) levels and HDLc/ LDL-c ratio. The difference in cognitive performance among the groups was compared. Logistic regression model was used to determine the association of circulating cholesterol level with the risk of Mild Cognitive Impairment (MCI). Results: Mild increase of serum LDL-c level correlated with better visual and executive, language, memory and delayed recall abilities. Higher circulating TC and HDL-c levels were found to be associated with poorer cognitive function, especially in aging female subjects. Higher circulating TC, HDL-c and HDL/LDL ratio indicated an increased risk of MCI, especially in female subjects. Conclusion: Slight increase in circulating LDL-c level might benefit cognitive function in aging adults. However, higher circulating TC and HDL-c levels might indicate a decline of cognitive function, especially in aging female subjects.

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Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-306764 ◽

2015 ◽

Vol 100 (9) ◽

pp. 838-844 ◽

Cited By ~ 14

Author(s):

Dag Sulheim ◽

Even Fagermoen ◽

Øyvind Stople Sivertsen ◽

Anette Winger ◽

Vegard Bruun Wyller ◽

...

Keyword(s):

Working Memory ◽

Cognitive Function ◽

Processing Speed ◽

Sleep Problems ◽

Verbal Learning ◽

Chronic Fatigue ◽

Cross Sectional Study ◽

Cognitive Inhibition ◽

Sectional Study ◽

Cross Sectional

ObjectiveTo compare cognitive function in adolescents with chronic fatigue with cognitive function in healthy controls (HC).Study designCross-sectional study.SettingPaediatric department at Oslo University Hospital, Norway.Participants120 adolescents with chronic fatigue (average age 15.4 years; range 12–18) and 39 HC (average age 15.2 years; range 12–18).MethodsThe adolescents completed a neurocognitive test battery measuring processing speed, working memory, cognitive inhibition, cognitive flexibility, verbal learning and verbal memory, and questionnaires addressing demographic data, depression symptoms, anxiety traits, fatigue and sleep problems. Parents completed the Behaviour Rating Inventory of Executive Function (BRIEF), which measures the everyday executive functions of children.ResultsAdolescents with chronic fatigue had impaired cognitive function compared to HC regarding processing speed (mean difference 3.3, 95% CI 1.1 to 5.5, p=0.003), working memory (−2.4, −3.7 to −1.1, p<0.001), cognitive inhibition response time (6.2, 0.8 to 11.7, p=0.025) and verbal learning (−1.7, −3.2 to −0.3, p=0.022). The BRIEF results indicated that everyday executive functions were significantly worse in the chronic fatigue group compared to the HC (11.2, 8.2 to 14.3, p<0.001). Group differences remained largely unaffected when adjusted for symptoms of depression, anxiety traits and sleep problems.ConclusionsAdolescents with chronic fatigue had impaired cognitive function of clinical relevance, measured by objective cognitive tests, in comparison to HC. Working memory and processing speed may represent core difficulties.

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Abstract 36: Association of Parental Stroke with Cognitive and Brain MRI Measures in Offspring - The Framingham Heart Study

Stroke ◽

10.1161/str.43.suppl_1.a36 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

GALIT WEINSTEIN ◽

Alexa Beiser ◽

Rhoda Au ◽

Charles DeCarli ◽

Philip A Wolf ◽

...

Keyword(s):

Executive Function ◽

Brain Injury ◽

Verbal Learning ◽

Brain Mri ◽

Abstract Reasoning ◽

Parental History ◽

Brain Volumes ◽

Regional Brain ◽

Increased Risk ◽

History Of

Objectives- Parental stroke is related to an increased risk of stroke among the offspring. Vascular related brain changes, however, often occur before clinical stroke and the association of parental history of stroke and structural brain measures and cognition has not been fully explored. We hypothesized that prospectively verified parental stroke will be associated with increased vascular brain injury and poorer cognitive performance. Methods- A total of 1,297 Framingham offspring (mean age: 61 ± 9 years, 54% women) were studied. Of these, 9.9% had prospectively identified stroke in one or both parents before age 65. Volumetric brain MRI measures of total cerebral brain volume (TCBV), regional brain volumes, white matter hyperintensity volume (WMHV), and covert brain infarcts (CBI) and performance on tests of verbal memory, abstract reasoning, verbal learning and visuospatial memory (VRd) were compared for offspring with and without parental history of stroke. All measures were assessed cross-sectionally and longitudinally (mean duration of follow-up was 6.1±1.2 years). We used models adjusted only for age, sex, education and also additionally adjusted for vascular risk factors and for WMHV as an index of subclinical vascular brain injury. GEE models were used to adjust for sibling relationships among offspring. Results- Higher WMHV (β±SE=0.17±0.08;p=0.027) and lower VRd scores (β±SE=-0.80±0.34; p=0.017) at baseline were found in offspring with parental history of stroke. In addition, participants with parental stroke by age 65 years were more likely to be in the highest quintile of increase in WMHV (OR=1.87;p=0.04) as well as worsening executive function (Trails B-A) (OR:1.81;p=0.03). Parental stroke was not associated with total and regional brain volumes or with memory, abstract reasoning and verbal learning. Conclusions- In our community-based sample of middle-aged asymptomatic subjects, the occurrence of parental stroke by age 65 years is associated with higher baseline WMHV and with a more rapid increase in WMHV. Further, parental stroke is also associated with poorer performance on VRd and a decline in executive function. The effects on baseline WMH and VRd were substantial equivalent to 2.8 and 7 years of brain aging, respectively.

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Increased Brain Age Gap Estimate (BrainAGE) in Young Adults After Premature Birth

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.653365 ◽

2021 ◽

Vol 13 ◽

Author(s):

Dennis M. Hedderich ◽

Aurore Menegaux ◽

Benita Schmitz-Koep ◽

Rachel Nuttall ◽

Juliana Zimmermann ◽

...

Keyword(s):

Premature Birth ◽

Brain Aging ◽

Structural Mri ◽

Full Term ◽

Intracranial Volume ◽

Age Gap ◽

Increased Risk ◽

Aging Rates ◽

Brain Age ◽

Premature Born

Recent evidence suggests increased metabolic and physiologic aging rates in premature-born adults. While the lasting consequences of premature birth on human brain development are known, its impact on brain aging remains unclear. We addressed the question of whether premature birth impacts brain age gap estimates (BrainAGE) using an accurate and robust machine-learning framework based on structural MRI in a large cohort of young premature-born adults (n = 101) and full-term (FT) controls (n = 111). Study participants are part of a geographically defined population study of premature-born individuals, which have been followed longitudinally from birth until young adulthood. We investigated the association between BrainAGE scores and perinatal variables as well as with outcomes of physical (total intracranial volume, TIV) and cognitive development (full-scale IQ, FS-IQ). We found increased BrainAGE in premature-born adults [median (interquartile range) = 1.4 (−1.3–4.7 years)] compared to full-term controls (p = 0.002, Cohen’s d = 0.443), which was associated with low Gestational age (GA), low birth weight (BW), and increased neonatal treatment intensity but not with TIV or FS-IQ. In conclusion, results demonstrate elevated BrainAGE in premature-born adults, suggesting an increased risk for accelerated brain aging in human prematurity.

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Association of Atrial Fibrillation With White Matter Disease

Stroke ◽

10.1161/strokeaha.118.023386 ◽

2019 ◽

Vol 50 (4) ◽

pp. 989-991 ◽

Cited By ~ 2

Author(s):

Iris Yuefan Shao ◽

Melinda C. Power ◽

Thomas Mosley ◽

Clifford Jack ◽

Rebecca F. Gottesman ◽

...

Keyword(s):

Atrial Fibrillation ◽

White Matter ◽

Mean Diffusivity ◽

Brain Magnetic Resonance Imaging ◽

White Matter Disease ◽

Linear Regression Models ◽

Cross Sectional ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Microstructural Integrity

Background and Purpose— Evidence suggests that atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. White matter disease (WMD) is a potential mechanism linking AF to cognitive impairment. In this study, we explored the association between prevalent AF and WMD. Methods— We performed a cross-sectional analysis of participants attending the ARIC-NCS (Atherosclerosis Risk in Communities–Neurocognitive Study) in 2011 to 2013 who underwent brain magnetic resonance imaging. AF was ascertained from study visit electrocardiograms or prior hospitalization codes. Extent of WMD was defined by measures of white matter (WM) microstructural integrity and WM hyperintensity volume. Multivariable linear regression models were used to assess the association between AF and WMD. Results— Among 1899 participants (mean age, 76 years; 28% black; 60% women), 133 (7%) had prevalent AF. After multivariable adjustment, differences between participants with and without AF were −0.001 (95% CI, −0.006 to 0.004) for global WM fractional anisotropy, 0.031×10 −4 mm 2 /s (95% CI, −0.075 to 0.137) for global WM mean diffusivity, and 0.08 mm 3 (95% CI, −0.14 to 0.30) for WM hyperintensity volume. Conclusions— The results suggest that there is no association between prevalent AF and WMD.

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Gender Differences in Plasma Vitamin C Concentrations and Cognitive Function: A Pilot Cross-Sectional Study in Healthy Adults

Current Developments in Nutrition ◽

10.1093/cdn/nzaa038 ◽

2020 ◽

Vol 4 (4) ◽

Cited By ~ 1

Author(s):

Nikolaj Travica ◽

Karin Ried ◽

Irene Hudson ◽

Avni Sali ◽

Andrew Scholey ◽

...

Keyword(s):

Cognitive Function ◽

Vitamin C ◽

Verbal Learning ◽

Cross Sectional Study ◽

Healthy Adults ◽

Plasma Vitamin ◽

Motor Speed ◽

Cognitive Assessments ◽

Cross Sectional ◽

And Gender

ABSTRACT Background A number of investigations have highlighted the importance of vitamin C in maintaining brain health. Biologically, vitamin C has exhibited roles in neuromodulation, neurodevelopment, vascular support, and neuroprotection. Vitamin C's contribution to cognitive function in both cognitively intact and impaired cohorts has previously been assessed, with little focus on gender variability. Objective The present study explored the interaction between gender and plasma vitamin C on cognitive performance, and the effect of different amounts of plasma vitamin C (adequate/inadequate) on various cognitive tasks by gender. Methods This retrospective analysis was conducted in healthy adults (n = 80, female = 52, male = 28, 24–96 y) with a range of blood plasma vitamin C concentrations. Cognitive assessments included the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and 2 pen-and-paper tests, the Symbol Digits Modalities Test (SDMT) and the Hopkins Verbal Learning Test–Revised (HVLT-R). Food-frequency questionnaires were used to elucidate dietary consumption. Results After adjusting for a number of potential covariates such as age, number of prescribed medications and dose of vitamin C supplementation, results indicated a significant interaction (P < 0.001) between plasma vitamin C and gender on cognitive function, on both the computerized and pen-and-paper assessments. A novel finding was that the performance of males with inadequate plasma vitamin C was poorer on tasks involving components of memory (short/delayed), inhibition, and visual perception, whereas females presenting with inadequate vitamin C were more compromised on tasks involving psychomotor performance/motor speed. Additionally, females with adequate vitamin C concentrations exhibited higher performance than males on tasks involving recall, recognition, attention, and focus. Conclusions Further larger-scale investigations are required to establish a cause-and-effect relation and to elucidate whether differences in cognitive function between genders may be attributed to plasma vitamin C status. This trial was registered at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440&isReview=true as ACTRN12615001140549.

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Individual variations in ‘brain age’ relate to early-life factors more than to longitudinal brain change

eLife ◽

10.7554/elife.69995 ◽

2021 ◽

Vol 10 ◽

Author(s):

Didac Vidal-Pineiro ◽

Yunpeng Wang ◽

Stine K Krogsrud ◽

Inge K Amlien ◽

William FC Baaré ◽

...

Keyword(s):

Early Life ◽

Brain Aging ◽

Average Rate ◽

Aging Brain ◽

Imaging Data ◽

Cross Sectional ◽

Polygenic Scores ◽

Longitudinal Imaging ◽

Brain Age ◽

Brain Change

Brain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain age models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features. The results showed no association between cross-sectional brain age and the rate of brain change measured longitudinally. Rather, brain age in adulthood was associated with the congenital factors of birth weight and polygenic scores of brain age, assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

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Individual variations in “Brain age” relate to early life factors more than to longitudinal brain change

10.1101/2021.02.08.428915 ◽

2021 ◽

Cited By ~ 1

Author(s):

D. Vidal-Piñeiro ◽

Y. Wang ◽

SK. Krogsrud ◽

IK. Amlien ◽

WFC. Baaré ◽

...

Keyword(s):

Early Life ◽

Brain Aging ◽

Average Rate ◽

Aging Brain ◽

Individual Change ◽

Imaging Data ◽

Cross Sectional ◽

Polygenic Scores ◽

Longitudinal Imaging ◽

Brain Age

AbstractBrain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher than expected brain age is thought partially to reflect above-average rate of brain aging. We explicitly tested this assumption in two large datasets and found no association between cross-sectional brain age and steeper brain decline measured longitudinally. Rather, brain age in adulthood was associated with early-life influences indexed by birth weight and polygenic scores. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

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