Want to keep your brain sharp as you age? Study finds two key factors

 

 Does your competent? doctor have EXACT PROTOCOLS to restore the cognitive reserve you lost because of your stroke? Doesn't even know of the need? 

PURE INCOMPETENCE!

Want to keep your brain sharp as you age? Study finds two key factors

As people grow older, maintaining a sharp mind becomes a priority for many. While some changes in memory and thinking are often considered a natural part of aging, researchers continue to explore why some older adults seem to retain their cognitive abilities far better than others. 

New research examining adults over the age of 65 offers some clues. Across two studies, scientists investigated the factors linked to stronger performance on tasks involving language, memory and information processing. 

The findings suggest that certain resources built and developed over a lifetime may help support healthier cognitive aging. 

One of the key concepts explored by researchers was cognitive reserve, which they define as the mental resources people accumulate through education, intellectually stimulating jobs and mentally engaging hobbies and leisure activities. According to the studies, this reserve may help the brain better cope with age-related changes. 

The first study focused on language abilities, examining how effectively older adults could retrieve words and express themselves. 

Researchers found that participants with higher levels of cognitive reserve performed better on language tasks. In some cases, their abilities were similar to those seen in younger adults. Positive emotions were also associated with stronger language performance. 

One of the study’s most notable findings came from an analysis of verbal fluency during the first 10 seconds of a task. 

While traditional assessments typically focus on performance across a full minute, researchers were interested in the opening moments, when people rapidly search their memory for words. They found that signs of age-related decline could already be detected during those first few seconds. 

However, the decline was much smaller among people with higher cognitive reserve and, in some cases, appeared to disappear altogether. 

The researchers concluded that cognitive reserve may help preserve more youthful language abilities, particularly when it comes to quickly retrieving words. 

The study also highlighted the role of emotion in language processing. Older adults retrieved words associated with positive emotions more easily than words linked to negative emotions, suggesting that both cognitive reserve and emotional content can influence language performance later in life. 

The second study examined working memory, the ability to temporarily hold information, process it and use it to complete a task. Researchers note that working memory generally becomes less efficient with age. 

To investigate the factors that may help support it, adults over 65 completed a working-memory task involving faces. Depending on the test condition, participants were asked to focus either on a person’s age or on their emotional expression. 

Researchers wanted to determine whether cognitive reserve and emotional intelligence played a greater role when emotional information was relevant to the task. 

Once again, cognitive reserve emerged as a significant factor. 

Participants with higher cognitive reserve performed better overall, were more accurate and benefited regardless of which version of the task they completed. According to the researchers, this suggests that cognitive reserve plays a fundamental role in helping people maintain and manipulate information needed to complete tasks. 

The results also showed that older adults performed better when emotional information was involved, suggesting emotional content may help make cognitive processing more efficient. 

Researchers also examined emotional intelligence, defined as the ability to recognize, understand and use emotions. Participants with higher emotional intelligence took longer to respond to emotional stimuli, which researchers said likely reflected deeper processing rather than greater difficulty. 

Taken together, the findings suggest that cognitive reserve and emotional skills work together to support healthy cognitive aging. Cognitive reserve appears to benefit both language and working memory, while emotional abilities influence how efficiently older adults process information. 

Experts say reserve can be strengthened through lifelong learning, regular exercise, mentally stimulating activities, social engagement and other enriching experiences.

The work was conducted as part of the Italian research program Age-It: Ageing Well in an Ageing Society, which studies the challenges and opportunities associated with an aging population. 

Reference: 

Rumiati. Brain Sciences. DOI: 10.3390/brainsci16070725 

Contact Newsweek editors on this story: Kara Dolman and Gray R. Thomas

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Healthy aging: Training the mind and emotional skills helps keep the brain healthy

 Does your competent? doctor have EXACT PROTOCOLS to restore the cognitive reserve you lost because of your stroke? Doesn't even know of the need? 

PURE INCOMPETENCE!

Healthy aging: Training the mind and emotional skills helps keep the brain healthy

Two studies from SISSA show that cognitive reserve built over a lifetime, together with emotional resources, helps preserve mental abilities in adults over 65

Peer-Reviewed Publication

Scuola Internazionale Superiore di Studi Avanzati, intellectually stimulating work, and an active lifestyle help preserve cognitive abilities in adults over 65, leading to more effective verbal expression and stronger cognitive performance. But there is another important factor: emotions. The way we recognize and interpret them can significantly influence the efficiency of cognitive processes as we age.

These findings emerge from two new studies conducted by the laboratory of Professor Raffaella Rumiati at theScuola Internazionale Superiori di Studi Avanzati (SISSA) in Trieste, Italy, recently published in Neuropsychology and Brain Sciences. The researchers examined how a group of adults over the age of 65 performed on various tasks to identify factors that help preserve cognitive function later in life.

The first authors of the two studies, Elisabetta Pisanu and Stefania Lucia, focused in particular on the role of cognitive reserve—the set of mental resources accumulated throughout life through education, professional experience, and intellectually engaging leisure activities. The first study found that individuals with greater cognitive reserve performed better in language tasks, showing a greater ability to express themselves and retrieve the right words. Positive emotions also contributed to better language performance.

The second study showed that cognitive reserve also plays a key role in supporting working memory—the ability to temporarily retain, process, and use information to complete a task. Emotions also influence these cognitive processes: they not only improve performance, but also shape the way we respond to different stimuli. In particular, higher emotional intelligence, i.e. the ability to recognize, understand, and use emotions to guide thinking, behaviour, and relationships, was found to significantly influence participants' responses to emotional stimuli.

Overall, the findings confirm that an intellectually stimulating life helps preserve cognitive function as we grow older. They also suggest that cognitive and emotional resources do not operate independently but work together to support healthier and more efficient cognitive ageing. Both studies were carried out as part of Age-It: Ageing Well in an Ageing Society, a major Italian research programme investigating the challenges and opportunities associated with population ageing.

Finding the right words: Cognitive reserve and emotions shape language in later life

Cognitive reserve helps preserve language abilities as we age. The study published in Neuropsychology found that older adults with greater cognitive reserve maintained better language performance than their peers.

“Our findings show that older adults with higher cognitive reserve achieve language performance comparable to that of younger adults,” explains Elisabetta Pisanu, first author of the study. “In our experiments, we focused on what happens during the first ten seconds of a verbal fluency task, when people search for the right words to express their thoughts. This brief time window captures the fastest and most automatic processes involved in word retrieval, without the need for the traditional one-minute test. We found that these first ten seconds are already sufficient to reveal the effects of both ageing and cognitive reserve on language performance.”

The researchers observed that a decline in performance is already detectable during these initial moments in adults over 65. However, this decline is greatly reduced, and may even disappear, in individuals with high cognitive reserve. “In other words,” the researchers explain, “cognitive reserve helps keep the brain ‘young’, at least when it comes to language and word retrieval.”

The study also found that not all words are equally easy to retrieve. According to Pisanu: “Older adults retrieve words associated with positive emotions more easily than those linked to negative emotions. These findings suggest that, alongside the protective role of cognitive reserve, the emotional valence of words also contributes to language performance.”

Ageing and working memory: Experience and emotions support cognition in different ways

As we grow older, working memory—the ability to temporarily hold, process, and use information to complete a task—also tends to become less efficient. The study published in Brain Sciences investigated how cognitive reserve and emotional intelligence contribute to working memory, particularly when emotions are relevant to the task at hand.

To address this question, the researchers asked a group of adults over the age of 65 to complete a working memory task in which, depending on the condition, they had to focus either on the emotional expression or on the age of the faces presented to them. “We wanted to understand whether cognitive reserve and emotional intelligence play different roles depending on whether emotions are relevant—or irrelevant—to a working memory task,” explains Stefania Lucia, first author of the study.

The findings showed that cognitive reserve improves performance regardless of the type of task. “Our results indicate that cognitive reserve enhances performance accuracy independently of the experimental condition,” says Lucia. “This suggests that it plays a fundamental role in supporting the ability to maintain and manipulate the information needed to carry out a task.” The role of emotions also emerged clearly. “When the task involves emotional content, older adults perform better: they appear to become more efficient,” Lucia observes. Emotional intelligence, in turn, influences the way people process information and respond to the task.

“It affects how individuals process information and generate a response, ultimately shaping their performance. For example, people with higher emotional intelligence take longer to respond to emotional stimuli, probably because they devote greater attentional and cognitive resources to processing them. This does not reflect greater difficulty, but rather deeper and more thorough processing of emotional information.”

Raffaella Rumiati: Understanding cognitive ageing is a scientific and societal challenge

“Both of these studies were carried out as part of Age-It: Ageing Well in an Ageing Society, an ambitious national research programme that has laid the foundations for a research and data infrastructure dedicated to the study of ageing from multiple perspectives, including socio-economic, biomedical, and technological dimensions,” says Raffaella Rumiati, neuroscientist at SISSA and principal investigator of both studies.

“Italy is one of the world's longest-lived countries, together with Japan. While this is an extraordinary achievement, it also brings new challenges. As the older population continues to grow, so does the demand for healthcare and long-term care services. Understanding how to preserve cognitive abilities for as long as possible is therefore essential—not only to improve people's quality of life, but also to help ensure the sustainability of healthcare and social welfare systems.” According to Rumiati, cognitive decline and the strategies to counteract it are among the major challenges of an ageing society.“Our research can contribute in two important ways: by improving the methodological tools used to study cognitive ageing, and by identifying the factors that help protect cognitive functions as people grow older.”

She concludes: “Our findings show that an intellectually stimulating life helps preserve a wide range of cognitive functions, from language to working memory. They also highlight the important role of emotions, which, as our studies suggest, make a significant contribution to the efficiency of cognitive processes. Taken together, these findings indicate that cognitive reserve and emotional skills contribute to healthier and more efficient cognitive ageing. These are promising results that we intend to explore further in future studies.”

---

Journal

Brain Sciences

DOI

10.3390/brainsci16070725 

The aging brain that doesn’t fail: how neural resilience masks neurodegeneration

Have your competent? doctor provide you EXACT PROTOCOLS for cognitive reserve and resilience. A competent? doctor would have distributed the recovery protocol that Pedro Bach-y-Rita  used to recover fully back in 1958 with only a partial brain! But you don't have a competent doctor, do you? Hasn't done anything so you can be like Bernadette the nun? Lost the link but your doctor should know about her.

NO? So, willing to DO NOTHING, LIKE USUAL!

cognitive reserve (51 posts to November 2014)
cognitive resilience (18 posts to September 2014)

cognitive rehabilitation (34 posts to December 2015)

 The aging brain that doesn’t fail: how neuralresilience masks neurodegeneration

Andrew Eisen , Heather D. Durham & Erik Pioro To cite this article: Andrew Eisen , Heather D. Durham & Erik Pioro (27 Jul 2026): The aging brain that doesn’t fail: how neural resilience masks neurodegeneration, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, DOI: 10.1080/21678421.2026.2705693 To link to this article: https://doi.org/10.1080/21678421.2026.2705693

ANDREW EISEN 1 2 1 , HEATHER D. DURHAM 2 & ERIK PIORO 1 Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, and Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada 

Abstract 

 Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer’s disease, and Parkinson’s disease are usually framed as consequences of aging-related pathogenic processes, including impaired proteostasis with protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Yet, most individuals, even into advanced age, do not develop clinically significant neurodegenerative disease. This discrepancy suggests that the nervous system possesses robust and redundant protective mechanisms that maintain neural integrity despite cumulative molecular and cellular stress. In this perspective, we propose that neurodegenerative diseases arise not simply from the presence of pathogenic processes, but when integrated resilience systems fail to maintain homeostasis or when reserve mechanisms no longer compensate for accumulated pathology. We have synthesized a threshold-based model of disease emergence based on evidence across proteostasis, mitochondrial function, neuroimmune regulation, glial biology, network-level compensation, and barrier integrity, while integrating genetic, environmental, developmental, and stochastic modifiers. We distinguish biological resilience, which actively limits or repairs pathology, from reserve, which permits function despite pathology. We further propose that clinical disease emerges only when age-related cumulative stress exceeds the combined capacity of resilience and reserve. Reframing neurodegeneration as a failure of preservation systems offers new directions for pre vention and therapeutic development. 

Keywords: Aging, neurodegeneration, senescence, resilience 

Cognitive-motor network integration as a behavioral marker of cognitive reserve in post-stroke rehabilitation

 This did nothing to answer the real need! HOW EXACTLY DO YOU REBUILD COGNITIVE RESERVE post stroke so you can weather getting dementia/Alzheimers (per Bernadette the nun) and not have problems?

Cognitive-motor network integration as a behavioral marker of cognitive reserve in post-stroke rehabilitation

• 

  Katharina Kreiger 1,2*

• E

  Elisabeth Weiss 1

• 

  Felix Fluri 2,3

• 1. Faculty of Psychology, University of Innsbruck, Innsbruck, Austria

• 2. Kliniken Valens, Rheinburg Klinik, Walzenhausen, Switzerland

Abstract

Background:

Functional recovery after stroke varies substantially between individuals, even after standardized inpatient rehabilitation. Cognitive reserve is increasingly considered a key determinant of recovery potential, yet it is typically approximated using indirect proxy measures that may not capture the underlying functional mechanisms of recovery. Network-based approaches may provide a more mechanistic operationalization of cognitive reserve.

Objective: 

This study investigated whether (a) traditional cognitive reserve proxies predict rehabilitation response, (b) responders differ from non-responders in respect to baseline cognitive performance structure, and (c) rehabilitation response is associated with greater cross-domain cognitive-motor network integration at admission.

Methods: 

In this retrospective cohort study, 100 patients (≥ 65 years) with ischemic stroke were included. Functional outcomes were assessed using a battery of motor tests at admission and discharge. A responder was defined as someone who improved in at least two functional domains. Cognitive performance was assessed using the CERAD battery. Cognitive reserve proxies included years of education and engagement in leisure activity domains. Group differences and predictors of responder status were examined using regression models controlling for stroke severity (NIHSS).

Results: 

Cognitive leisure activities emerged as the strongest predictor of responder status (OR = 4.84), whereas education and other leisure domains were not retained. Exploratory factor analysis revealed two baseline cognitive dimensions (Memory, Executive-Spatial), but responders did not show significantly higher baseline cognitive scores. Network analyses demonstrated a more integrated cognitive-motor architecture in responders, characterized by higher density and lower sparsity. Dexterity and delayed verbal recall showed the highest centrality in the responder network, alongside processing speed as a consistently contributing node across centrality indices.

Conclusion: 

Post-stroke cognitive reserve may be less dependent on a high cognitive performance or demographic proxies but may be due to a more integrative organization of cognitive-motor functioning. Our findings support a network-based conceptualization of cognitive reserve with direct implications for integrative rehabilitation strategies.

More at link.

RNA gene expression and cognitive reserve as determinants of post-ischaemic stroke cognitive recovery

 

Biomarkers do nothing for recovery unless you are mapping EXACT RECOVERY PROTOCOLS to them! You're all fired for useless shit!

RNA gene expression and cognitive reserve as determinants of post-ischaemic stroke cognitive recovery

Abstract

Cognitive impairment is a common yet under-recognised complication of ischaemic stroke (IS), with long-term effects on patient quality of life and rehabilitation outcomes. Identifying early biomarkers and protective factors such as cognitive reserve (CR) is essential for improving prognosis and guiding targeted interventions. This study aimed to determine the following: (i) RNA gene expression profiling during acute stroke and (ii) the associations between target genes as well as clinical factors and cognitive impairment during an acute event and at the 3-month follow-up. A three-month prospective cohort study involving 24 adults with mild to moderate IS and 24 age- and sex-matched controls admitted to Hospital Canselor Tuanku Muhriz, Malaysia, was conducted. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) within 48 h of stroke and at 3 months. Peripheral blood samples were collected for RNA extraction, and gene expression was analysed using RT² Profiler PCR arrays. Cognitive reserve was measured using the Cognitive Reserve Index Questionnaire (CRI-q). Statistical analyses included chi-square and independent t tests. At baseline, 83.3% of IS patients exhibited cognitive impairment (mean age 64.6 ± 10.5 years). Increased age (p = 0.006), low education level (p = 0.010), diabetes mellitus (p = 0.010), CRI-Education (p = 0.010) and CRI-Working Activity (p = 0.009) were significantly associated with baseline cognitive impairment. These clinical and CR factors survived False Discovery Rate (FDR) correction at the baseline stage (p < 0.05). However, at the 3-month follow-up, no clinical or CR factors remained statistically significant after FDR correction. Regarding gene expression, while MAPK1 (p = 0.029) and CAPZB (p = 0.042) were nominally upregulated in patients, and RCOR1 (p = 0.043) showed a nominal association with baseline impairment, no genetic markers survived FDR correction at either time point. Age, diabetes, and cognitive reserve are robust determinants of cognitive status during the acute phase of ischaemic stroke. The loss of significance at 3 months suggests these factors are primary drivers of initial functional buffering rather than long-term recovery trajectories in this cohort. CR should be utilised as a prognostic stratification tool during admission to identify high-risk patients rather than as a direct target for acute intervention. Future large-scale studies are required to validate whether the observed nominal gene expression trends can serve as reliable biomarkers for long-term recovery.

Does Brain Reserve Attenuate the Effects of Alzheimer Disease Pathology?

 

Have your competent? doctor give you EXACT PROTOCOLS TO BUILD BRAIN RESERVE and thus prevent dementia post stroke! Oh, can't or won't do that? INCOMPETENCE PERSONIFIED! Fire them! 

(My cognitive reserve was obviously high enough to withstand the stroke quite well. But NO one can tell me how or if I can build it up again to prevent dementia.)

Does Brain Reserve Attenuate the Effects of Alzheimer Disease Pathology?

Greater brain reserve and higher socioeconomic status were associated with reduced cognitive vulnerability to Alzheimer disease pathology among cognitively unimpaired older adults.

Greater cognitive and brain reserve may buffer the cognitive consequences of Alzheimer disease (AD) pathology, according to a study published in Neurology.

Researchers from AdventHealth Research Institute in the United States evaluated whether measures of cognitive and brain reserve modified the relationship between AD pathology and cognitive performance using baseline data from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study (ClinicalTrials.gov Identifier: NCT02875301). 

Adults (N=621) aged 65 to 80 years who were cognitively unimpaired and physically inactive between 2017 and 2020 underwent cognitive assessment, magnetic resonance imaging (MRI), and plasma sampling for phosphorylated tau (p-tau) 217. A subset of participants (n=355) also underwent positron emission tomography (PET). The primary outcome was the effect of brain-predicted age difference (brain-PAD) and volumetric AD phenotype on cognitive performance. Objective socioeconomic status (SES) was calculated as a composite of annual family income, total savings, debt-adjusted savings, and duration of standard of living maintenance if current income was lost.

 

[W]e found some evidence that higher SES weakens the relationship between AD pathology and cognitive function, highlighting the need for further research in this area and to address socioeconomic inequalities…

The study population was 71% women and 75% White, with a mean (SD) age of 69.9 (3.8) years. The participants had completed a mean (SD) of 16.3 (2.2) years of education, and mean (SD) objective SES was 0.0 (0.91). In addition, 27% were apolipoprotein E (APOE) ε4 carriers, mean (SD) Montreal Cognitive Assessment (MoCA) score was 25.8 (2.6), and mean (SD) p-tau217 level was 0.43 (0.28) pg/mL.

The cohort had a mean (SD) brain-PAD of -4.05 (6.7) years and a mean (SD) AD signature of 64,958.6 (5387.4) mm3.

The AD signature was negatively correlated with brain-PAD (r, -0.204; P ≤.001) and positively correlated with executive function/attentional control (r, 0.217; P ≤.001), working memory (r, 0.214; P ≤.001), processing speed (r, 0.197; P ≤.001), visuospatial function (r, 0.193; P ≤.001), and episodic memory (r, 0.132; P ≤.001).

Years of education (β range, 0.18-0.30; all P <.001) and objective SES (β range, 0.11-0.21; all P <.004) were significantly associated with cognitive performance across domains. However, years of education did not moderate the relationship between p-tau217 and cognitive outcomes.

Significant brain-PAD-by-p-tau217 interactions were observed for working memory (β, -0.10; P <.01), episodic memory (β, -0.09; P <.05), processing speed (β, -0.08; P <.05), and executive function/attentional control (β, -0.08; P <.05). When AD signature was included in the brain-PAD moderation analysis, brain-PAD continued to interact with p-tau217 levels for working memory (β, -0.10; P =.008), episodic memory (β, -0.08; P =.025), and executive function/attentional control (β, -0.07; P =.044).

Volumetric AD signature did not moderate the relationship between p-tau17 or PET centiloids and cognitive outcomes.

Study limitations include the cross-sectional design, lack of PET data from the full cohort, and limited generalizability because the population was relatively well educated and predominantly non-Hispanic White.

The study authors concluded, “These results suggest that greater brain reserve may help buffer the cognitive consequences of AD pathology.” They continued, “In addition, we found some evidence that higher SES weakens the relationship between AD pathology and cognitive function, highlighting the need for further research in this area and to address socioeconomic inequalities as contributors to improving brain health.”

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

A 'Youthful' Brain May Boost Alzheimer's Resilience

 Ask your competent? doctor EXACTLY how to have a youthful brain! No knowledge, fire them and have them fired for incompetence! Dead wood needs to be removed unceremoniously! They do know exactly why Bernadette the nun was able to function quite well even with Alzheimers? NO? They incompetently know nothing about Bernadette? That's a game changer showing complete incompetence!

A 'Youthful' Brain May Boost Alzheimer's Resilience

Key Takeaways

• Preserved global brain structure appeared to buffer cognitive decline in people with Alzheimer's pathology.
• Younger-appearing brains had weaker links between pathology and poorer outcomes in multiple cognitive domains.
• Other measures of brain reserve or cognitive reserve showed no clear protective cognitive effect.

Greater structural brain integrity appeared to buffer the cognitive consequences of Alzheimer's disease pathology, cross-sectional data suggested.

The study evaluated two markers of brain reserve -- brain-predicted age difference (brain-PAD) and a volumetric Alzheimer's disease signature -- in cognitively unimpaired older adults. Brain-PAD, a marker of overall structural brain health, uses MRI data to determine how much older or younger a brain appears relative to chronological age.

Two markers of cognitive reserve, socioeconomic status and years of education, also were assessed.

Brain-PAD moderated the association between Alzheimer's pathology and multiple cognitive domains, including episodic memory (β = -0.09), processing speed (β = -0.08), working memory (β = -0.10), and executive function/attentional control (β = -0.08), reported Kelsey Sewell, PhD, of Murdoch University School of Allied Health in Perth, Australia, and co-authors."Specifically, the negative association of greater Alzheimer's disease pathology with poorer cognition was weakest in individuals with younger-appearing brains," the researchers wrote in Neurology.

A latent socioeconomic status score also appeared to influence the relationship between Alzheimer's pathology and episodic memory (β = 0.08), but the association did not remain significant after correction for multiple comparisons, Sewell and colleagues noted. Neither years of education nor the volumetric Alzheimer's signature moderated pathology-cognition associations, they added.

"Our main finding was that maintaining good overall brain health may help reduce the impact of Alzheimer's‑related changes on cognitive function," Sewell said in a statement. "Things like exercise, maintaining a healthy diet, sleeping well, and finding new cognitive challenges can help to maintain a healthy brain."

About 20% to 30% of adults ages 65 to 75 show evidence of Alzheimer's pathology despite having no measurable cognitive impairment, Sewell and co-authors said. "This phenomenon is often attributed to resilience, a general term describing multiple reserve-related processes that enable the brain to maintain higher levels of cognitive performance and function with aging or disease," they wrote."Within this framework, two key concepts are 'cognitive reserve' defined as a property of the brain that allows for cognitive performance better than expected given the degree of brain changes and pathology, and 'brain reserve' defined as the neurobiological capacity of the brain at a given point in time," they stated.

The findings of this study support "the idea that preserved global brain structure reduces vulnerability to cognitive decline in the face of emerging pathology," noted Maria Carrigan, MSc, and Colin Groot, MSc, both of Amsterdam University Medical Center in the Netherlands, in an accompanying editorial.

"For clinicians, the key message is that preserved global brain health seems to matter even before symptoms emerge," Carrigan and Groot wrote.

"The study also raises important questions for future research," the editorialists added. "What biological processes underlie a younger-appearing brain? To what extent is brain-PAD modifiable through interventions targeting physical activity, vascular risk factors, or other lifestyle exposures? In addition, how does brain-PAD interact longitudinally with amyloid and tau accumulation to influence cognitive trajectories?"

Sewell and colleagues examined whether cognitive and brain reserve modified the relationship between Alzheimer's pathology and cognition in 621 cognitively unimpaired, physically inactive participants in the IGNITE exercise trial in the U.S.

Mean age was 70 years and 71% were women. The mean brain-PAD of the cohort was -4.05, indicating that participants' brains appeared younger than their chronological age, on average.

Alzheimer's pathology was assessed using plasma phosphorylated tau (p-tau)-217. A subgroup of 355 participants also underwent tau PET imaging. Brain age was estimated from T1-weighted images.

The researchers noted several limitations. The study was cross-sectional and could not determine causality: while accelerated brain aging might worsen the cognitive effects of Alzheimer's pathology, it's also possible that people with more advanced brain ages are more vulnerable to accumulating pathology.

Emerging evidence suggests that p-tau217 may not be entirely specific to Alzheimer's pathology, they acknowledged. Findings from participants who had tau PET imaging supported the associations seen in the study.

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

Sewell had no disclosures. One co-author disclosed being an inventor on a University of Pittsburgh patent regarding the IPMS assay for Aβ peptides and serving as a consultant for Quanterix.

Carrigan and Groot had no relevant disclosures.

Primary Source

Neurology

Source Reference: Sewell KR, et al "Cognitive and brain reserve as modifiers of early Alzheimer disease-related cognitive vulnerability" Neurology 2026; DOI: 10.1212/WNL.0000000000214833.

Secondary Source

Neurology

Source Reference: Carrigan M, Groot C "Can a 'youthful' brain moderate vulnerability to Alzheimer disease?" Neurology 2026; DOI: 10.1212/WNL.0000000000214927.