Study Maps Accelerated Brain Aging Signatures Across 9 Conditions

 Your competent? doctor has to prevent MCI post stroke! WHAT ARE THE EXACT PROTOCOLS TO DO THAT? Sorry, there aren't any, are there?

Study Maps Accelerated Brain Aging Signatures Across 9 Conditions

Summary: Researchers evaluated structural MRI scans from 45,900 controls and 2,698 individuals across 9 conditions to map brain aging signatures. Measuring Predictive Age Difference (PAD), the team found that Alzheimer’s disease and mild cognitive impairment showed the highest accelerated brain aging, followed by psychiatric disorders and substance addiction.

ADHD and autism showed no increase in PAD. The study mapped distinct regional aging patterns, such as default mode network involvement in addiction and frontal-temporal acceleration in psychiatric conditions, offering new structural biomarkers for clinical neuroscience.

Key Facts

• Accelerated Aging Rankings: Neurodegenerative conditions (Alzheimer’s disease and MCI) showed the highest overall positive PAD (most pronounced accelerated brain aging), followed by psychiatric disorders and substance addictions.
• Neurodevelopmental Divergence: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) showed no significant increase in PAD compared to healthy controls, indicating that neurodivergence does not equate to accelerated structural brain aging.
• Regional Aging Signatures:
  • Prefrontal Cortex: Exhibited elevated PAD broadly across multiple brain disorders.
  • Frontal & Temporal Lobes: Showed elevated PAD specifically associated with psychiatric disorders.
  • Frontal & Occipital Cortex: Showed localized accelerated aging signature patterns in dementia.
  • Default Mode & Salience Networks: Showed selective elevated PAD tied to alcohol and tobacco addiction, alongside structural shifts in the putamen and thalamus.
• Transcriptomic Link: Regional PAD maps correlated with condition-specific gene transcription patterns, offering biological insights into the pathways underlying accelerated structural decline.

Source: PLOS

People with dementia, mild cognitive impairment, alcohol addiction, or psychiatric disorders such as schizophrenia show increased brain aging, each in specific patterns within the brain, according to a study published July 21^st in the open access journal PLOS Medicine by Shile Qi from the Nanjing University of Aeronautics and Astronautics, China, and colleagues.

Some conditions can make the brain age faster. Scientists calculate how old the brain is relative to the body using the predictive age difference (PAD), the difference between chronological age and the age predicted by brain imagine, where a positive PAD indicates that aging is accentuated or increased.

To better understand how brain disorders and divergences might affect brain aging, the authors of this study collected structure magnetic resonance imaging (MRI) data from 45,900 controls across several brain imaging banks, and compared them with of 2,698 patients with different brain conditions and differences, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), alcohol or tobacco addiction, Alzheimer’s disease (AD), mild cognitive impairment (MCI), schizophrenia, bipolar disorder or major depressive disorder.

The authors found that neurodegenerative disorders of AD and MCI had the largest association with a high PAD. Addiction and psychiatric disorders were also associated with increased PAD. In contrast, there were no differences in PAD between people with ADHD or ASD and controls.

The researchers also looked at PAD values in specific areas of the brain, and examined which genes showed increased expression in people with different brain conditions.

The prefrontal cortex showed higher PAD across brain disorders. Higher PAD in the frontal and temporal lobes was associated with psychiatric disorders, while high PAD in the frontal and occipital cortex was associated with dementia.

Addiction was connected with high PAD in the default mode network, and in the salience network and the putamen and thalamus. There were also differences in gene transcription that associated with specific conditions and divergences.

While the results are correlational, and not causal, and while some conditions such as psychiatric disorders and addiction have high co-occurrence, the author suggest that understanding more about PAD could help provide biomarkers for commonly occurring brain disorders.

The authors add, “Different neurological disorders appear to leave different signatures on the brain aging clock, which may help researchers better understand the neural and biological pathways involved in these conditions.”

Funding: This work was supported by the Key Research and Development Plan of Jiangsu Province, China (BE2023668, https://kxjst.jiangsu.gov.cn) to S.Q., and the National Natural Science Foundation of China (62376124, https://www.nsfc.gov.cn) to S.Q. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Key Questions Answered:

Q: What is Predictive Age Difference (PAD) and how is it measured?

A: Predictive Age Difference (PAD) is calculated by comparing a person’s actual chronological age with their estimated “brain age,” derived from structural MRI scans analyzed via machine learning algorithms. A positive PAD value indicates that the structural features of the brain resemble those of a chronologically older individual, signaling accelerated brain aging.

Q: Do all mental health conditions accelerate brain aging?

A: No. While neurodegenerative conditions (like Alzheimer’s and MCI), psychiatric disorders (like schizophrenia and major depression), and addictions (alcohol and tobacco) showed increased PAD, neurodevelopmental conditions like ADHD and autism spectrum disorder (ASD) showed no increase in brain aging compared to healthy controls.

Q: Why are regional “signatures” of brain aging important for clinical research?

A: Broad brain aging metrics only tell part of the story. By mapping accelerated aging to specific circuits, such as the default mode network in addiction or the temporal lobe in psychiatric illness, researchers can identify distinct biological pathways, potential biomarkers for early diagnosis, and targeted circuit interventions.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this neurology and brain aging research news

Author: Claire Turner
Source: PLOS
Contact: Claire Turner – PLOS
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Brain aging patterns among nine neurological disorders: A case-control study” by Chuang Liang, Godfrey Pearlson, Juan Bustillo, Peter Kochunov, Jiayu Chen, Xiangrong Zhang, Rongtao Jiang, Kent E. Hutchison, Jing Sui, Zening Fu, Xiao Yang, Yuhui Du, Daoqiang Zhang, Shile Qi, Vince D. Calhoun. PLOS Medicine
DOI:10.1371/journal.pmed.1004860

Sensorimotor function associated with mild cognitive impairment

 

Margaret Yekutiel wrote a whole book about this in 2001, 'Sensory Re-Education of the Hand After Stroke'.

Of course, your competent? doctor put together somatosensory protocols from this earlier research a long time ago to prevent cognitive impairment, right? Oh no, you DON'T have a functioning stroke doctor, do you? Too bad, it's your problem to solve since your stroke hospital board of directors is fucking incompetent in running their hospital! 25 years of incompetence! WOW, that's got to be a record for staying incompetent!

I bet your doctor isn't competent enough to get this research going in stroke subjects!

Sensorimotor function associated with mild cognitive impairment

Key takeaways:

• The links between sensory and motor impairments and mild cognitive impairment remain poorly understood.
• These associations persisted across two large cross-sectional cohorts.

Higher sensorimotor function was associated with reduced likelihood of mild cognitive impairment in two cohorts of older individuals, according to findings published in Alzheimer’s & Dementia.

“Identifying precursors to mild cognitive impairment (MCI) — the transitional stage between unimpaired cognition and dementia — is a public health priority,” Amal A. Wanigatunga, PhD, MPH, FACSM, assistant professor of epidemiology, Johns Hopkins Bloomberg School of Public Health, and colleagues, wrote.

Data derived from Wanigatunga AA, et al. Alz & Dem. 2026;doi:10.1002/alz.71332.

The potential links between sensory and motor impairments and MCI remain poorly understood, according to the researchers. “Their integrated contribution as a sensorimotor construct remains underexplored,” they wrote.

Wanigatunga and colleagues analyzed cross-sectional data from the Atherosclerosis Risk in Communities (ARIC; n = 880; 63,4% women) and Baltimore Longitudinal Study of Aging (BLSA; n = 681; 56.8% women). The mean age of participants in the ARIC cohort was 78.9 years, while the mean age of the BLSA cohort was 74.4 years, according to the findings.

Eligibility criteria stipulated that individuals with stroke, Parkinson’s disease or dementia were excluded from the study.The researchers compiled a composite score for sensorimotor function that included variables such as hearing, vision, olfaction, balance, gait speed, and grip strength.

Assessment of participants in the ARIC cohort showed that 59% had unimpaired balance, while 71% had unimpaired walking speed, 65% had unimpaired strength and performance, and 61% demonstrated unimpaired handgrip strength. Sensory function data showed that 42% had unimpaired hearing, 27% reported unimpaired vision, and 84% reported unimpaired olfaction.

The researchers added that participants in the ARIC cohort demonstrated more unimpaired motor and sensory function prevalence than the BLSA cohort, including parameters of balance, upper extremities motor strength and vision.

Results showed that higher sensorimotor function carried an inverse association with MCI in individuals from both the ARIC cohort (OR = 0.53; 95% CI, 0.4–0.71) and the BLSA cohort (OR = 0.59; 95% CI, 0.43–0.81).

This trend persisted across adjusted analyses for age, race, sex, education and BMI in both cohorts. Moreover, morbidity and depressive symptoms also failed to reduce the significance of the associations.

“Sensorimotor function appears robustly related with MCI in a large sample of older adults,” Wanigatunga and colleagues concluded. “These findings highlight the potential value of incorporating sensorimotor assessments in early detection for cognitive decline.”

Six Gut Markers May Identify Early Cognitive Decline

 Can your competent? doctor see the need for this testing and have available THE EXACT PROTOCOLS to prevent such decline?

Six Gut Markers May Identify Early Cognitive Decline

Blood tests detected metabolic shifts associated with nascent cognitive impairment

Key Takeaways

• Six diet- and gut-derived metabolites identified early cognitive impairment in older adults in a small study.
• The metabolite panel distinguished healthy controls from those with mild or subjective cognitive impairment.
• Findings suggest that metabolic disruptions may occur before clinical symptoms of dementia.

Six blood metabolites produced by or associated with gut microbiota identified early cognitive impairment in a small study.

The circulatory metabolites -- 5-hydroxyindole acetic acid, indole-3-propionic acid, choline, indoxyl sulfate, kynurenic acid, and kynurenine -- distinguished cognitively healthy older adults from those with mild cognitive impairment with an area under the curve (AUC) of 0.79, reported David Vauzour, PhD, of the University of East Anglia in Norwich, England, and co-authors.

The metabolites also separated healthy controls from people with subjective cognitive impairment with an AUC of 0.75, Vauzour and colleagues wrote in Gut Microbes. "This study shows that a small set of gut‑ and diet‑derived blood metabolites can reliably distinguish healthy aging from early cognitive decline, even at the very earliest stage," Vauzour told MedPage Today.

The panel of six metabolites reflects early metabolic disruption along the gut-brain axis, he noted. "These results highlight that metabolic alterations appear long before cognitive decline is clinically apparent, offering a non‑invasive and scalable approach for early risk identification," Vauzour said.

"Because circulating metabolites integrate both gut microbial activity and host physiology, they outperform microbiome‑only metrics and offer promising avenues for early detection, monitoring, and targeted intervention strategies," he added.

Recent research showed that the composition of the gut microbiome correlated with amyloid and tau markers in people with asymptomatic Alzheimer's disease. Growing evidence also suggests that changes to gut bacteria may be linked to dementia risk, noted Sheona Scales, PhD, of Alzheimer's Research UK, which supported the study."While current blood tests for Alzheimer's work by detecting levels of specific proteins linked with the disease, this research may offer a new avenue for future blood test development," Scales wrote on the U.K. Science Media Centre website.

"This study can't say whether people with early memory and thinking problems will go on to develop dementia, but it identifies an interesting area for further research," she pointed out. "Given the study involved a relatively small group of people, larger and longer-term studies are needed to build on these findings and understand whether this type of test could be used alongside existing ones."

Vauzour and co-authors studied 150 older adults: 50 cognitively healthy controls, 50 participants with subjective cognitive impairment, and 50 with objectively measured mild cognitive impairment.

Groups were matched on age, sex, and body mass index. The mean age across groups was 65.5 years and 54% were women. Blood and fecal sample data came from baseline measurements of two previously conducted clinical studies.

Participants were excluded if they had a history of significant neurologic, psychiatric, gastrointestinal, or metabolic disorders; chronic fatigue syndrome; or gallbladder abnormalities. Additional exclusion criteria included current or recent smoking, alcohol or drug dependency, and clinically significant depression or anxiety. Individuals were ineligible if they were taking antidepressants, antipsychotics, anticoagulants, or any medications affecting gastrointestinal function.

Mass spectrometry platforms analyzed 33 metabolites in serum -- 13 tryptophan-related compounds, 15 bile acid compounds, three trimethylamine N-oxide-related metabolites, and two cresol metabolites. Microbiome analysis using 16S rRNA amplicon sequencing was used to detect bacterial taxa associated with metabolic changes.

The researchers used multiple linear regression and machine learning techniques to identify a metabolite panel capable of classifying early cognitive decline. Of the six metabolites in the panel, all except choline were products of tryptophan metabolism.

"The work underscores tryptophan metabolism as a key pathway disrupted early in cognitive decline, with protective metabolites decreasing and inflammatory or toxic metabolites increasing," Vauzour said. "The observation that biological changes arise at the subjective cognitive impairment stage further supports the need to shift prevention efforts earlier in the disease trajectory."While the study adjusted for key covariates, metabolome profiles can be influenced by a plethora of environmental and biological factors, the researchers acknowledged. Metabolite changes may reflect physiological states associated with systemic inflammation, for example. "Thus, although our findings suggest relationships between the variables, we cannot infer causal relationships from this analysis alone," they wrote.

Future work should validate these metabolite signatures in larger, independent cohorts and across more diverse populations, Vauzour suggested.

"Longitudinal studies are needed to determine whether these metabolic changes can predict conversion from subjective cognitive impairment to objective cognitive impairment, and eventually, dementia," he stated. "Mechanistic studies, including microbiome manipulation or dietary interventions, could help clarify causal pathways and support the development of personalized, metabolite‑guided prevention strategies."

Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Connect:

Disclosures

The microbiota analysis in this study was supported by an Alzheimer's Research UK Small Pump Priming Grant.

Vauzour and co-authors reported no competing interests.

Scales had no disclosures.

Primary Source

Gut Microbes

Source Reference: Connell E, et al "Circulatory dietary and gut-derived metabolites predict early cognitive decline" Gut Microbes 2026; DOI: 10.1080/19490976.2026.2649487.

γ-Oryzanol, a unique ingredient specific to brown rice, effectively restores mild cognitive impairment (MCI) in obese aged mice by ameliorating microglial inflammation and promoting neurogenesis in hippocampus: Novel therapeutic insight into obesity-associated MCI

Ask your competent? doctor and hospital when research will determine if this also applies to humans and non-obese persons and stroke survivors with their higher risk of dementia?

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

 γ-Oryzanol, a unique ingredient specific to brown rice, effectively restores mild cognitive impairment (MCI) in obese aged mice by ameliorating microglial inflammation and promoting neurogenesis in hippocampus: Novel therapeutic insight into obesity-associated MCI

Shiki Okamotoa,b , Ikumi Nomuraa, Ayano Kinjoc, Yuko Murayamaa, Chie Horiguchia, Chisayo Kozukad , Taiki Teruyaa, Tsugumi Uemaa Michio Shimabukuroe , Tomoko Nagaic, , Chitoshi Takayamaf Masayuki Matsushitag, Keiko Abeh , and Hiroaki Masuzakia* aDivision of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Gradu ate School of Medicine, University of the Ryukyus, Okinawa 901-2720, Japan bLaboratory of Veterinary Physiology and Biochemistry, Yamaguchi University Joint Graduate School of Veterinary Medicine, Yamaguchi 753-8515, Japan cSENTAN Pharma Inc., R&D Department, Fukuoka 812-0027, Japan dLaboratory for Epigenome Inheritance, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan eDepartment of Diabetes, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan fDepartment of Molecular Anatomy, School of Medicine, University of the Ryukyus, Okinawa 901-2720, Japan gDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 901-2720, Japan hDepartment of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan *Corresponding author: Hiroaki Masuzaki, Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, 901-2720, Japan. E-mail: hiroaki@ cs.u-ryukyu.ac.jp DOI: 10.26599/JFB.20xx.000xx Received: January 17, 2026; Revised received & accepted: February 06, 2026 Abbreviations: CI, cognitive impairment; Orz, γ-oryzanol; Nano-Orz, nanoparticulated γ-oryzanol; FITC, fluorescein isothiocyanate; LCD, lab chow diet; HFD, high-fat diet; PO, per os Citation: Okamoto, S., Nomura, I., Kinjo, A., Murayama, Y., Horiguchi, C., Kozuka, C., Teruya, T., Uema, T., Nagai, T., Shimabukuro, M., Takayama, C., Matsushita, M., Abe, K., and Masuzaki, H. (2026). γ-Oryzanol, a unique ingredient specific to brown rice, effectively restores mild cognitive impairment (MCI) in obese aged mice by ameliorating microglial inflammation and promoting neurogenesis in hippocampus: Novel therapeutic insight into obesity-associated MCI. J. Food Bioact. 000: 000–000. 

Abstract 

Obesity-diabetes syndrome poses a considerable risk for mild cognitive impairment (MCI). Our study was designed to explore therapeutic potential of γ-oryzanol (Orz), a brown rice-specific oil composed of ferulic acid ester with several phytosterols, on MCI in high-fat diet (HFD) induced obese aged mice. After being housed on an HFD for 4 months, regular Orz or the nanoparticulated form of Orz (Nano-Orz), which markedly enhances its intestinal absorption, was administered to aged mice. Mice treated with regular Orz for 4 months exhibited significant improvement in spatial cognitive function. Impressively, mice treated with Nano-Orz demonstrated cognitive improvement as early as 1 month, with substantial recovery by 3 months. In the hippocampus, treatment with both regular Orz and Nano-Orz upregulated genes associated with neurogenesis and stem cell function accompanied by a significant increase in gene expressions of anti-inflammatory cytokines. Our data highlight a therapeutic potential of Orz for obesity-associated MCI. 1. Introduction Mild cognitive impairment (MCI) stems from a variety of factors, including aging, chronic inflammation, and beta-amyloid accumu lation in the hippocampus. Of note, obesity has recently been rec ognized as a considerable risk for MCI, highlighting that chronic over-ingestion of a high-fat diet (HFD) substantially impairs hip pocampus-dependent memory in both rodents and humans (Ka noski and Davidson, 2010; Kanoski et al., 2007; Nyaradi et al., 2014; Sharma, 2021). γ-Oryzanol (Orz), a brown rice-specific oil composed of ferulic acid ester with several phytosterols, is known to act preferentially on lipophilic organs and tissues (Masuzaki et al., 2019). A line of our studies showed that orally administered Orz accumulated considerably in the brain and pancreas, thereby reducing exaggerated endoplasmic reticulum (ER) stress by sup pressing mRNA expression of ER stress-associated genes (Chop, ERdj4, Xβp1) in both hypothalamus and pancreatic β-cells in HFD-induced obese diabetic mice (Kozuka et al., 2015; Kozuka, Shimizu-Okabe, et al., 2017). We also demonstrated in mouse ex periments that Orz potently inhibited DNA methyltransferases, thereby reducing animal fat preference via epigenetic modulation of dopamine receptor gene in brain reward system (Kozuka, Kan ame, et al., 2017). Moreover, a rat model of streptozotocin-induced sporadic Alzheimer’s disease showed that Orz was potent to delay the onset of MCI (Jha and Panchal, 2017). To date, detailed molecular mechanisms whereby Orz would improve MCI have been poorly elucidated. Furthermore, due to extremely poor solubility in water of Orz, oral administration of Orz in mice provided a weak impact on some effects (Kozuka et al., 2013). To overcome such a hazard, we previously reported that oral administration of nanoparticulated γ-oryzanol (Nano Orz) in mice markedly enhanced absorption efficiency from intestine by more than 1,000-fold (Kozuka, Shimizu-Okabe, et al., 2017). In this context, we here provide evidence that oral administration of Nano-Orz potently mitigates hippocampal dys function via novel mechanisms, thereby improving MCI in obese aged mice. 

More at link.

Lifetime Risk Estimates for Dementia, MCI: New Data

 Your risk is definitely higher post stroke; BUT YOUR COMPETENT? DOCTOR HAS EXACT PROTOCOLS TO PREVENT THAT, RIGHT?

Nope! You got one of the incompetent? ones, didn't you!

Lifetime Risk Estimates for Dementia, MCI: New Data

TOPLINE:

Lifetime risk for dementia and mild cognitive impairment (MCI) was 43% and 62%, respectively, in adults aged 55 years or older, new research showed. Additionally, the onset of MCI occurred 10 years earlier than the onset of dementia, women had a higher lifetime risk for both conditions, and Black individuals had an earlier age of onset.

METHODOLOGY:

• Researchers pooled data from five cohort studies at Rush Alzheimer’s Disease Center for more than 4600 community-dwelling event-free adults aged 55-105 years (mean age at baseline, 77 years; 75% female; 28% Black individuals) for dementia analyses. Nearly 4000 of these participants were also assessed for MCI.
• At annual standardized clinical evaluations, participants reported their medical histories and underwent neurologic examinations and neuropsychological testing.
• Researchers assessed lifetime risk for incident dementia and incident MCI, accounting for the competing risk for death, with participants stratified by age, sex, race, and history of stroke.

TAKEAWAY:

• From age 55 to 105 years, the lifetime risk was 43% for incident dementia and 62% for incident MCI — with the risk increasing sharply after age 75 and 65 years, respectively. Approximately 84% of cases for both conditions were diagnosed between 75 and 95 years of age.
• Women had a higher lifetime risk than men for dementia (45% vs 39%) and MCI (63% vs 59%), and their diagnoses occurred approximately 2 years later (P < .05).
• Black participants had a slightly higher overall risk for dementia than White participants (45% vs 43%) and were diagnosed about 5 years earlier (P < .001). The overall risk for MCI was lower in Black participants than in White participants (59% vs 64%), but Black participants had a higher cumulative incidence at age 55-75 years (15% vs 10%) and were diagnosed a median of about 6 years earlier (P < .001).
• Exploratory analyses showed a significant association between stroke and increased risk for both dementia (hazard ratio [HR], 1.4; P < .001) and MCI (HR, 1.3; P < .003).

IN PRACTICE:

“These findings extend lifetime risk estimation beyond age 90 and highlight the need for equitable, culturally informed dementia prevention and monitoring strategies,” the investigators of the study wrote.

SOURCE:

The study was led by Lianlian Du, PhD, Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago. It was published online on February 03 in Alzheimer’s & Dementia.

LIMITATIONS:

The study population primarily comprised Black, White, and urban-dwelling individuals, with a limited number of Latino participants and no Asian American participants, which potentially affected generalizability. Genetic and cohort effects were not examined. Additionally, the apparent plateau in the cumulative incidence analysis after age 95 years warrants careful interpretation because analyses indicated continued increases in risks for dementia or MCI and mortality.

DISCLOSURES:

The study was funded by the National Institute on Aging. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, 

Neuroprotective, Antioxidant and Anti-Inflammatory Effect of Greek Pomegranate Seed Oil on N2a Neuroblastoma Cells and Mild Cognitive Impairment Patients

What did your competent? doctor do as takeaways from this research? NOTHING, like usual? It has been 8 months; 8 months is a long time to be incompetent!

Neuroprotective, Antioxidant and Anti-Inflammatory Effect of Greek Pomegranate Seed Oil on N2a Neuroblastoma Cells and Mild Cognitive Impairment Patients

Eleni E Tzekaki 1 2, Georgios Katsipis 1 2, Athanasios Chatzikostopoulos 2 3, Anna Koutoupa 3, Sophia N Lavrentiadou 2 4, Magda Tsolaki 2 3, Anastasia A Pantazaki 1 2

Affiliations 

• PMID: 40427737
 
• PMCID: PMC12109235
 
• DOI: 10.3390/biology14050548

Abstract

Alzheimer's disease (AD) remains a significant global health challenge with limited FDA-approved treatments, necessitating the search for novel preventive strategies. Antioxidants that are present in fruits and vegetables have garnered attention due to their potential neuroprotective effects. Among these, pomegranate (Punica granatum L.) has emerged as a promising source of neuroprotective antioxidants as it is rich in polyphenols, flavonoids, and hydrolysable tannins. Pomegranate seed oil (PSO) is a source of bioactive compounds that may modulate key pathological processes of AD. This study investigated the therapeutic potential of PSO in murine neuroblastoma N2a cells treated with lipopolysaccharide (LPS) to simulate AD-like inflammation. The effects of PSO on inflammation and oxidative stress markers, including TNF-α, iNOS, SOD1, and IL1β, were evaluated, along with changes in AD-related biomarkers Aβ42, Aβ40, and p-tau181. Additionally, the study extended its findings to clinical settings by assessing the impact of supervised PSO consumption for 12 months on similar biomarkers in patients with mild cognitive impairment. Results from this integrative approach demonstrated the anti-inflammatory and antioxidant potential of PSO, supporting its role in modulating AD-associated pathophysiology. These findings suggest that PSO may serve as an early-stage intervention to delay or mitigate AD progression, highlighting its therapeutic potential in preclinical and clinical contexts.

Keywords: Alzheimer’s disease; antioxidant therapy; mild cognitive impairment; neuroinflammation; pomegranate seed oil.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

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Changes in Driving Patterns May Signal Early Cognitive Decline

 

Your competent? doctor already knew about this earlier research, right? Oh no, you DON'T have a functioning stroke doctor, do you?

Driving Patterns Pinpoint Early Alzheimer's Disease July 2021

And your patient's health will deteriorate after stopping driving.

Health goes downhill when older adults stop driving 

The latest here:

Changes in Driving Patterns May Signal Early Cognitive Decline

A change in driving patterns may be an indicator of cognitive decline in older adults, a long-term study suggested.

Using driving data, researchers were able to predict the development of mild cognitive impairment (MCI) with 82% accuracy. Over 3 years, compared with those with normal cognition, older adults with MCI drove less at night, made fewer monthly trips, and did not stray as much from regular routes.

“We found that using a GPS [Global Positioning System] data tracking device, we could more accurately determine who had developed cognitive issues than looking at just factors such as age, cognitive test scores, and whether they had a genetic risk factor related to Alzheimer’s disease,” principal investigator Ganesh M. Babulal, PhD, OTD, of Washington University School of Medicine in St. Louis, said in a news release.

The study was published online on November 26 in Neurology.

New Opportunities for Early Detection

In the US, older adults make up roughly 20% of drivers. In addition, an estimated one third of this population experiences cognitive impairment. Previous studies have shown that those with early-stage dementia scored worse on driving tests and had a greater risk of a crash.

Timely, scalable solutions are needed to monitor safety in this at-risk population of drivers, the researchers noted, highlighting that recent advances in vehicular tracking technology might provide useful data to identify MCI.

To test this hypothesis, the investigators analyzed driving data from 298 participants (mean age, 75.1 years; 45.6% female). Of these, 56 were older adults with MCI, while the rest had normal cognition (NC).

Participants underwent the Clinical Dementia Rating, a series of neuropsychological assessments, and were genotyped for the APOE epsilon 4 allele, a known risk factor for Alzheimer’s disease. Investigators calculated individuals’ Preclinical Alzheimer Cognitive Composite (PACC) score based on results from a battery of standardized cognitive tests.

An in-vehicle GPS tracker recorded participants’ driving behavior daily for up to 40 months, capturing total trips, average distance, nighttime driving, speeding episodes, and route variation.

Changes in longitudinal driving behavior were assessed using a linear mixed model, adjusted for baseline age, race, education, sex, and APOE epsilon 4 status. Logistic regression with receiver operator curve analysis was used to distinguish older adults with MCI and those with NC.

At baseline, the driving habits of the NC and MCI groups were similar. However, over time, older adults with MCI made fewer trips per month (P < .001) and fewer nighttime trips (P < .001). They also drove more familiar routes, as evidenced by statistically significantly lower random entropy, a measure of trip unpredictability.

Specifically, driving factors like speeding, route variation, and medium and maximum distance were found to distinguish drivers with MCI from those with NC (area under the curve, 0.82; 95% CI, 0.75-0.89).

When demographic factors, PACC score, and APOE epsilon 4 status were added to the model, the investigators were able to identify MCI with 87% accuracy (95% CI, 0.81-0.93). Without the driving data, accuracy decreased to 76%.

“Looking at people’s daily driving behavior is a relatively low-burden, unobtrusive way to monitor people’s cognitive skills and ability to function,” Babulal said. “This could help identify drivers who are at risk earlier for early intervention, before they have a crash or near miss, which is often what happens now.”

The investigators noted that the study’s limitations included the fact that the majority of participants were predominantly White individuals and highly educated and that the data were not externally validated.

The study was supported by the National Institutes of Health and the National Institute on Aging. See the study for the full list of author disclosures.