Tag: Cognitive Function

Study finds J-shaped association between dietary thiamine intake and worsening mental acuity

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There seems to be a J-shaped curve between dietary thiamine (vitamin B1) and worsening mental acuity among cognitively healthy older people, suggests research published in the open access journal General Psychiatry.

The sweet spot seems to be a daily intake of 0.68 mg, below which there is relatively little impact. But higher daily intake was strongly associated with cognitive decline, with the optimal maintenance dose 0.6 to less than 1 mg/day, the findings show.

Thiamine is an essential water-soluble B vitamin involved in energy metabolism and brain neurotransmitter activity. Good dietary sources include whole grains, fortified breakfast cereals, legumes, liver, and salmon.

Small previously published studies suggest that high doses can improve cognitive function in people with mild cognitive impairment or early stage dementia. But it’s not clear if usual dietary intake is associated with slowing, or speeding up, cognitive decline.

To explore this further, the researchers used publicly available data from the China Health and Nutrition Survey (CHNS), a long term multipurpose study which began in 1989, and which included nearly half the country’s population by 2011.

In 1997, 2000, 2004 and 2006, mental acuity was repeatedly assessed for cognitively healthy participants aged 55 and above. The current study is based on 3106 participants, with an average age of 63, and at least two rounds of survey data.

Information on diet was collected in each survey round, supplemented by detailed data on personal dietary intake over 24 hours on 3 consecutive days of the week, and collected in person by trained investigators. Nutrient intake was calculated using the Chinese food composition tables.

Three tests of immediate and delayed recall of a 10-word list, counting backwards from 20, and serial subtraction of 7 five times from 100, taken from the Telephone Interview for Cognitive Status–modified (TICS-m), were used to evaluate verbal memory, attention, and numerical fluency, respectively.

A higher score for each item (including verbal memory [0-20 points], attention [0-2 points] and calculation [0-5 points]) indicates better cognitive function, with a global cognitive score ranging from 0 to 27 points and also a composite score ranging from -1.82 to 1.67 standard units.

The average monitoring period was nearly 6 years, during which time a J-shaped association emerged between dietary thiamine intake and the pace of decline in cognitive function over 5 years.

Average thiamine intake was 0.93 mg/day, but the threshold seemed to be a daily intake of 0.68 mg. There was no significant association with cognitive decline below this level.

But above 0.68 mg/day, each daily unit (1 mg/day) increase in thiamine intake was associated with a significant fall of 4.24 points in the global cognitive score and 0.49 units in the composite score within 5 years. Since the global cognitive score ranges from 0 to 27 points, a decline of about 4 points means a decline in cognitive function of at least 15%

These associations were stronger among those who were obese, had high blood pressure or who were non-smokers, although after further in depth analysis, the modifying effect of high blood pressure and smoking became statistically insignificant,

To further explore the optimal range of dietary thiamine for maintaining cognitive function, intake was further divided into 0.4, 0.6, 0.8, 1, 1.2 and 1.4 mg/day.

This showed that the lowest risk was associated with a thiamine intake of 0.6 to less than 1 mg/day. Similar patterns were also observed after accounting for daily intake of other B vitamins (riboflavin and niacin) and other foods, such as red or processed meat.

None of the other variables, including age, sex, alcohol consumption and dietary intake of fat, protein or carbohydrate, significantly changed the findings.

This is an observational study, and as such, can’t establish cause, acknowledge the researchers. And 24-hour dietary recall only captures information on specific days and may not be completely accurate. The study also focused on older people in China, so the findings may not be applicable to other nationalities and age groups, they add.

“Thiamine deficiency may lead to an insufficient supply of energy to the neurons of the brain and decreased acetylcholine signaling in the brain, which may impair cognitive function,” suggest the researchers, by way of an explanation for their findings.

“If substantiated by further research, our study highlights the importance of maintaining optimal dietary thiamine intake levels in the general older population to prevent cognitive decline.”

Source:

Journal reference:

Liu, C., et al. (2024). J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy, older Chinese individuals. General Psychiatry. doi.org/10.1136/gpsych-2023-101311.

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February 21, 2024
Study explores health benefits of selenium and zinc-enriched eggs

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In a recent study published in Nutrients, researchers investigated the effect of a diet of selenium- and/or zinc-enriched eggs (SZE) on oxidative stress, cognitive impairment, and intestinal flora in D-galactose-induced aging mice. They found that the SZE diet could reduce organ damage and improve cognitive function in mice models by modulating oxidative stress, inflammation, and gut microbiota.

Study: Selenium- and/or Zinc-Enriched Egg Diet Improves Oxidative Damage and Regulates Gut Microbiota in D-Gal-Induced Aging Mice. Image Credit: Timolina/Shutterstock.com

Background

The aging process involves an irreversible structural and functional decline influenced by genetics and the environment. It is characterized by an imbalance in reactive oxygen species (ROS), leading to cellular aging and age-related diseases. The essential trace elements selenium (Se) and zinc (Zn) have shown anti-aging effects linked to their roles in reducing ROS and combating oxidative stress. Although the individual roles and pathways of Se and Zn have been studied in mitigating the effects of aging, their combined effects of Se and Zn remain underexplored.

Eggs, recognized for their high nutritional value, contain essential nutrients like proteins, fatty acids, vitamins, and trace minerals, contributing significantly to the human diet and health. SZE represents an innovative approach to enhance mineral potency, with potential health benefits attributed to active substances like ovalbumin, ovoglobulin, and phosphatide. However, our understanding of SZE’s nutritional functions and biological activities is currently limited. Therefore, researchers in the present study aimed to explore the chemical composition of SZE and assess their potential efficacy in mitigating aging-related oxidative stress and inflammation, and promoting gut health in model mice.

About the study

Egg powders were developed from SZE and normal eggs (NE), and their composition was analyzed. Mineral content in the eggs was determined using inductively coupled plasma mass spectrometry (ICP-MS). In the in vivo analysis, 70 male Kunming mice were randomized into seven groups (n = 10 each). The groups were as follows: the control group (Con) was given 0.9% saline, the model group (Mod) given 0.9% saline, the low-dose SZE group (SZLE), the high-dose SZE group (SZHE), the ordinary eggs group (OE), the DL-Selenomenthionine group (SeM), and the ZnSO4 group (ZnSO4). All groups except Con were injected with D-galactose to induce aging.

Maze-based spontaneous alternation and cognitive function tests were conducted on the mice. Blood samples were collected and analyzed for levels of total superoxide dismutase (SOD), malondialdehyde (MDA), alanine transaminase (ALT), aspartate amino transferase (AST), and glutathione peroxidase (GSH-Px) were measured.

After an 8-week intervention, behavioral analysis, fasting, and euthanasia, tissues of the brain, liver, and duodenum, as well as cecum contents, were collected and analyzed. The organ index was calculated as the weight of the organ divided by body weight. Se and Zn content of the organs was measured.

Acetylcholine (Ach), acetylcholinesterase (AChE), and protein concentrations were measured in the brain tissue. Interleukin (IL)-6, IL-1β, and tumor necrosis factor α (TNF-α) levels were measured in the liver tissue using enzyme-linked immunosorbent assay (ELISA). Genomic DNA was extracted from the cecum contents, and the V3-V4 region of the bacterial 16S ribosomal ribonucleic acid (16S rRNA) region was amplified.

Results and discussion

While the moisture, lipid, and ash content were found to be similar in SZE and NE, the protein, sugar, Se, Zn, iron, manganese, molybdenum, magnesium, and phospholipid content of SZE was found to be higher than NE. Total cholesterol and other heavy metals were found to be lower in SZE than NE. Se was majorly enriched in the albumen, while Zn was enriched in the yolk.

In the in vivo analysis, researchers found that although the body weight of mice in Con and Mod groups increased initially, at the end of eight weeks, Mod mice showed reduction in organ index, indicating organ atrophy. This effect was attenuated in the groups SZE, OE, SeM, ZnSO₄, SZLE, and SZHE groups.

Se and Zn were majorly enriched in the brains of all the mice, and the levels varied across groups. The Mod group had significantly low levels of SOD and GSH-Px and significantly higher levels of MDA as compared to Con. The alternation rate and dwelling time in the new maze-arm were found to be significantly lower in the Mod groups as compared to Con. As measured by Ach and AChE levels, SZE was found to improve brain dysfunction induced by D-galactose. Similarly, based on interleukin, AST, and ALT levels, SZE intervention was also found to lower D-galactose-induced hepatic impairment and inflammation.

Further, the microbiota of all the groups was found to be very different. SZE helped maintain the balance of intestinal flora by significantly increasing the ratio of Firmicutes and Bacteroidota. The levels of Blautia were found to correlate with inflammatory markers and antioxidant levels.

Conclusion

The findings of the study demonstrate the promising role of SZE diet in mice, alleviating oxidative stress and improving gut microbiota balance. Further research exploring the therapeutic application of SZE diet in humans is warranted.

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February 15, 2024
Magnesium’s pivotal role in slowing aging’s impact
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Aging is associated with many biological, physiological, and psychological changes, some of which include a decline in cognitive function, greying of hair, frailty, and increased risk of contracting certain diseases. Aging also increases the risk of chronic diseases such as diabetes, hypertension, and cardiovascular events.

Most older adults experience chronic magnesium deficiency or hypomagnesemia, which may be due to low dietary magnesium content, reduced intestinal absorption, and increased urination. In a recent review published in the journal Nutrients, researchers discuss the role of magnesium in aging.

Study: Magnesium and the Hallmarks of Aging. Image Credit: monticello / Shutterstock.com

The role of magnesium in telomere attrition

Telomeres are present at both ends of chromosomes, thereby protecting them from degradation and fusion with other chromosomes to preserve genetic information. Between 50-100 base pairs of telomeric DNA are lost after each cell division; therefore, telomeres shorten as age advances.

When a telomere attains a critical short length, cells recognize it, and replication is attenuated, which results in cell senescence. Previous studies have indicated that magnesium maintains telomeric chromatin structure and integrity, as well as supports telomerase regulation.

Genomic instability

Genomic instability, which involves DNA damage, chromosomal abnormalities, and mutations, is a key driver of aging. Genomic instability occurs due to oxidative stress, epigenetic alterations, inadequate DNA repair, and telomere maintenance.

Throughout the cell cycle, magnesium is essential for stabilizing chromatin assembly. Furthermore, DNA grooves have specific binding sites for magnesium, thereby demonstrating its role in DNA conformation.

Insufficient magnesium levels cause DNA instability through oxidation stress, as various enzymes involved in DNA repair are activated by magnesium. Thus, magnesium plays a crucial role in the DNA replication process and preservation of genome stability.

Epigenetic alterations

Epigenetic alterations refer to the modification of genomic expression without alterations in DNA sequence. The epigenome can be altered through lifestyle factors, diets, and pharmaceutics. Additionally, the age-related inflammatory environment and inhibitory molecules released from stressed cells may lead to epigenetic alterations, which can modify cellular function.

Several studies have highlighted the association of magnesium with epigenetics. For example, hypomagnesemia causes down-regulation of hepatic 11β-hydroxysteroid dehydrogenase-2 (Hsd11b2) promoters, which affect the metabolism of neonatal offspring.

Loss of proteostasis

Proteostasis alterations are associated with weak protein stability and misfolded proteins. Several age-related chronic diseases, such as Alzheimer’s and Parkinson’s disease, have been attributed to the dysregulation of proteostasis. Importantly, low magnesium levels in the brain may lead to many neurological disorders, including epilepsy, Alzheimer’s disease, Parkinson’s disease, and migraines.

Magnesium downregulates tumor-necrosis factor α (TNF-α) and interleukin 1β (IL-1β) production, in addition to supporting the clearance of amyloid β (Aβ) precursor molecules by proteasomal degradation pathways. Magnesium also inhibits the N-methyl-D-aspartate (NMDA) receptor and increases excitatory neurotransmission.

Mitochondrial dysfunction

The mitochondria is involved in multiple cell signaling processes that determine cell fate, including cellular survival and death by apoptosis. Dysfunctional mitochondria can lead to the persistent reduction in cellular adenosine triphosphate (ATP) levels for prolonged periods, which may lead to chronic inflammation, cellular damage, and oxidative stress. These conditions are also linked with age-associated diseases, such as Alzheimer’s disease and Parkinson’s disease.

Magnesium binds with ATP to form the Mg-ATP complex. The presence of intracellular free magnesium has been associated with the development of hypertension and diabetes, both of which are conditions that are more prevalent in older adults. Low magnesium levels are also associated with oxidative stress damage through reduced lipid peroxidation and antioxidant enzyme activity.

Cellular senescence

Cellular senescence is associated with cellular stress and irreversible DNA damage. Additional features of aging include senescence-associated mitochondrial dysfunction, altered nutrient and stress signaling, and autophagy/mitophagy dysfunction.

Certain cellular alterations that occur during senescence are similar to those caused by hypomagnesemia, including reduced protection against oxidative stress damage, cellular viability, cell cycle progression, and enhanced risk of transcription factor expression.

Stem cell exhaustion

Human tissues are maintained by stem cells due to their self-renewing capacity. More specifically, stem cells can differentiate into progenitor cells, from which various tissues are developed.

Previous studies have shown that a reduction in the hemopoietic cells’ regenerative potential due to aging is associated with the reduced production of adaptive immune cells, which is otherwise known as immunosenescence.

Magnesium is strongly linked with immune responses. For example, magnesium is a cofactor for the production of immunoglobulins (Ig), antibody-dependent cytolysis, macrophage response to lymphokines, and immune cell adherence.

Conclusions

Since the aging trajectory is variable, it can be modulated through magnesium intake and lifestyle changes. The current review discusses the importance of suitable magnesium levels throughout life, which may contribute to healthy aging.
Journal reference:

Dominguez, L. J., Veronese, N., & Barbagallo, M. (2024). Magnesium and the Hallmarks of Aging. Nutrients 16(4); 496. doi:10.3390/nu16040496
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February 14, 2024
Study provides an important advancement of knowledge by showing neural compensation in healthy aging brains

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In a recent study posted to the eLife preprint server, researchers performed complete-brain voxel-wise functional magnetic resonance imaging (fMRI) to identify brain areas with functional-type compensation. They also investigated neurophysiological changes that maintain cognitive function in older adults.

Study: Neural Evidence of Functional Compensation for Fluid Intelligence in Healthy Ageing. Image Credit: LightField Studios/Shutterstock.com

*Important notice: Preprints publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Age-related functional compensatory mechanisms in the cognitive neurobiology of healthy aging are controversial, according to which older individuals increase brain activity to compensate for decreased cognitive ability. However, whether the additional brain activity helps cognitive performance is uncertain. Neuroimaging reveals that the human brain can adapt to tissue losses by increasing brain activities to sustain cognitive functioning. Age similarly influences fluid intelligence, a cognition skill.

About the study

In the present study, researchers used fMRI data from a fluid intelligence test to identify brain areas involved in functional compensation and understand brain responses to tissue loss. They also explored the relationship between age-related changes in brain activation and cognitive performance, specifically in fluid intelligence tasks.

The team analyzed data from 223 adult participants of the Cambridge Centre for Ageing Neuroscience (Cam-CAN) study to examine the relationship between age, cognitive performance, and brain activation patterns. Participants were aged 19 to 87 years, fluent in English, and mentally and physically fit, excluding those with MRI contraindications, poor mini-mental state examination (MMSE) scores, and psychiatric, medical, visual, or hearing impairments.

The team performed functional and structural neuroimaging to study the relationship between age, cognitive performance, and brain activation patterns. They performed a problem-solving task based on the modified Cattell Culture Fair Intelligence test during fMRI. They scanned participants during the Cattell fluid intelligence task, completing puzzles from two difficulty levels, to determine whether the candidate compensation regions exhibited multivariate evidence of compensation.

The dependent variables were the differences in functional MRI activation for hard vs. easy task blocks. The team used multivariate Bayesian decoding (MVB) to explore the role of multivoxel patterning in providing additional data related to task difficulty. They predicted that regions associated with functional compensation would have more data related to tasks with age. MVB was used to identify areas with additional multivariate data and support functional-type compensation, which involves the brain increasing activity to support cognitive functions in response to tissue loss.

To identify patterns of brain activation, the team overlaid maps testing for positive influences of age and performance on brain function, assessed using the hard vs. easy contrast. They used multiple regressions for analysis, with activation maps reflecting the unique effects of each. The team repeated multiple regression after scaling the influence of Cattell activation by estimating the resting state fluctuation amplitude (RSFA) for each region of interest (ROI) from an independent resting-state scan for each participant.

The team analyzed participant data using boxcar functions and statistical parametric mapping (SPM) hemodynamic response functions, fitting a model to each voxel. They defined functional compensation ROIs, the cuneal and frontal cortex by the empirical Bayes approach. They standardized and treated age and behavioral performance variables as linear predictors.

Results

Bilateral cuneal cortical activity increased with performance and age for hard vs. easy problems, even after adjusting for age-associated disparities in cerebrovascular reactivation. The cuneus region showed multivariate data supporting functional compensation, and age enhanced the likelihood of activation patterns, providing non-redundant data beyond the MDN work usually activated in the task.

The modified Cattell task showed a decrease in behavioral performance with age during fMRI scans. A strong correlation was found between fMRI and standard Cattell task performance measures when performed one to three years prior. Bilateral activation in multiple demand network (MDN) regions, including the intraparietal sulcus, middle/inferior frontal gyri, anterior cingulate cortical region, anterior insula, and lateral and ventral occipital temporal cortical region, was observed, probable due to the visual type of tasks like problem-solving and fluid intelligence.

Age-association increase in activity in the middle area of the frontal gyrus, precuneus, and motor supplementary areas was positively associated with performance in regions with higher activity for hard vs. easy tasks.

Two brain regions, the bilateral cuneal and frontal cortical regions, exhibited spatially overlapping positive influences of performance and age, indicating age-associated compensatory responses. However, the frontal area demonstrated additive influences of both study variables, while the cuneus area exhibited signs of interaction. The study found that age significantly influences performance as older individuals engage in compensatory patterns.

Conclusion

Overall, the study findings showed that healthy older individuals compensate for fluid intelligence during visual problem-solving tasks by increasing the recruitment of the bilateral cuneal cortex. The compensation allows the brain to react to the loss of tissue by increasing cognitive functions, known as functional compensation. Fluid intelligence, which involves solving abstract problems, declines with age. The MDN involvement in fluid-intelligence tasks tends to decrease with age. The cuneus region may play a role in functional compensation, and its activation increases with age.

*Important notice: Preprints publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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February 9, 2024
Gingko biloba compound injections linked to better stroke outcomes
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People with ischemic (clot-caused) stroke had better early recovery of cognitive function if treated with intravenous injections of a combination of biologically active components of ginkgo biloba during the first two weeks after the stroke, according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2024. The meeting will be held in Phoenix, Feb. 7-9, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Ginkgo biloba is an herb extracted from the dried leaves and seeds of the gingko tree, one of the oldest living tree species and native to East Asia. It is widely used in traditional Chinese medicine and available as a supplement in the U.S. Compounded therapies of the active ingredients of gingko biloba, delivered by IV, are widely used to treat stroke in China because of its potential antioxidant properties that may protect nerve cells from damage. Ginkgo biloba is not approved by the U.S. Food and Drug Administration for any medicinal use, and there is not enough evidence to support any non-FDA approved use, according to the National Center for Complementary and Integrative Health, a division of the National Institutes of Health.

In early 2023, researchers from this study published the results of a multicenter trial in China indicating that people with ischemic stroke had better recovery from their overall stroke symptoms if they were treated with daily injections of ginkgo diterpene lactone meglumine (GDLM), a combination of the biologically active components of ginkgo biloba. The current investigation analyzed the cognitive recovery of participants in that study.

If our positive results are confirmed in other trials, GDLM injections may someday be used to improve cognitive function for patients after ischemic stroke.”

Anxin Wang, Ph.D., associate professor of clinical epidemiology, Beijing Tiantan Hospital of the Capital Medical University, Beijing

The researchers analyzed the cognitive recovery of 3,163 stroke survivors (average age of 63 years; 36% women) treated for mild to moderate ischemic stroke at 100 centers in China. Starting within 48 hours of the stroke, about half of the stroke survivors were randomly selected to receive daily, intravenous injections of 25 mg of GDLM for 14 days, while the other half received daily, intravenous placebo injections. Cognitive performance was assessed before treatment, at 14 days and at 90 days using the Montreal Cognitive Assessment scale (MoCA), a 30-point face-to-face screening test of cognitive performance often used with stroke survivors. At baseline -; within 48 hours of the stroke and before beginning treatment, most patients’ cognitive status was moderately impaired, with an average score of 17 out of 30.

Compared to their initial cognitive screening results:
- By day 14, stroke survivors who received the ginkgo biloba compound injections had improved cognitive scores in comparison to those who received the placebo (an average of 3.93 points vs. 3.62 points higher, respectively); and
- By day 90, those who received the ginkgo biloba compound injections had even more improved cognitive scores compared to those who received the placebo (an average of 5.51 points vs. 5.04 points).
“The proportion of patients who reached a clinically significant level of improvement was 20% higher in the GDLM group, indicating that GDLM injections may improve cognitive function in patients with acute ischemic stroke,” Wang said. “Since the follow-up time in this study was only 90 days, the longer-term effect of GDLM injections requires longer-term research.”

“GDLM has shown a neuroprotective effect through multiple mechanisms, such as expanding brain blood vessels and improving brain cells tolerance to hypoxia (inadequate oxygen) and increasing cerebral blood flow. GDLM also has neuroprotective antioxidation, anti-inflammation and anti-apoptosis (cell death) properties,” Wang said. “Additionally, laboratory studies have previously indicated that GDLM may promote secretion of chemicals associated with avoiding neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease.”

In a 2022 American Heart Association Scientific Statement: Complementary and Alternative Medicines in the Management of Heart Failure, it was noted there may be some benefits and potentially serious risks to complementary and alternative medicines, so involving the health care team is critical.

“While this American Heart Association statement focused on the use of supplements in patients with heart failure, the same approach and caution should be used when treating all cardiovascular diseases including stroke,” said Chair of the scientific statement writing committee Sheryl L. Chow, Pharm.D., FAHA, an associate professor of pharmacy practice and administration at Western University of Health Sciences in Pomona, California, and an associate clinical professor of medicine at the University of California, Irvine. “Stroke patients should not take gingko biloba or other herbs or supplements without discussing it with their doctor and pharmacist. If this new research proves to be effective in future clinical trials it may be a valuable tool for after-stroke care; however, efficacy and safety would need to be demonstrated to meet the same standards as all prescription medications and secure FDA approval.” Dr. Chow was not involved in this study.

The study was an exploratory analysis conducted within a larger trial, so the results need to be confirmed in an independent trial. These results of adults in China may not be generalizable to people in other countries.

Source:

American Heart Association
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February 1, 2024