The Arising · The Mind

THE ARISING · LONGEVITY & HEALTHSPAN SUNDAY, OCTOBER 18, 2026 IN THIS EDITION · LONGEVITY & HEALTHSPAN 1 ACOG Now Recommends Hormone Therapy for Many Women With Hot Flashes 2 Cardiologists Urge Doctors to Prescribe Exercise as Routine Heart Care 3 Fasting and Autophagy in Humans: Summary Calls Link Unproven 4 Gut Supplements May Modestly Improve Cognition in Adults Over 60, Review Finds 5 Higher Ultra-Processed Food Intake Linked to Silent Brain Damage on MRI 6 Higher VO2 Max Linked to Lower Depression and Anxiety Risk in UK Biobank 7 Bonn Lab Study Shows Blood Cells From Older Donors Lose Epigenetic Age in a Dish 8 Longer Sleep Linked to Kidney Disease Risk in Type 2 Diabetes LONGEVITY & HEALTHSPAN · WEEKLY READ · 3 MIN AGE AND AGEING · 2 SOURCES Gut Supplements May Modestly Improve Cognition in Adults Over 60, Review Finds Gut supplements are cheap, easy to find and generally low risk. A new review asks whether they might also help older adults think a little more clearly. The answer, so far, is a cautious maybe: the average signal is small, the trials differ widely, and the evidence is limited. he evidence is a systematic review and meta-analysis, published in 2026 in the journal Age and Ageing. It pools earlier trials rather than running a newT one. The team, led by Mary Ni Lochlainn at King's College London, searched four medical databases for studies of adults aged 60 and over. They found 14 that qualified. Thirteen were randomised controlled trials and one was a non- randomised interventional study. Sample sizes in the individual studies ranged from 40 to 120 people. The studies tested three kinds of product. Probiotics are live bacteria. Prebiotics are food ingredients that feed beneficial gut microbes. Synbiotics combine the two. Ten studies tested probiotics, two tested prebiotics and two tested synbiotics. THE ARISING · OCTOBER 18, 2026 PAGE 11 Participants included cognitively healthy older adults (six studies), people with mild cognitive impairment (four) and people with dementia (four). The most common length of treatment was 12 weeks, and the longest was 24 weeks. Nine of the 14 studies reported a statistically significant improvement in at least one area of thinking. The areas named were global cognition (overall mental performance), memory, attention and executive function, which covers planning and mental flexibility. This is not the same as a clean win over placebo: in one dose- comparison trial, the placebo group also improved significantly in memory. Five studies did not report improvement. Two probiotic trials, one prebiotic trial and both synbiotic trials found no significant change in any area. Six of the randomised trials used the same test, the Mini-Mental State Examination, which scores overall cognition. The authors pooled these. Compared with placebo, supplements were linked to a gain of 1.28 points on the test (95% confidence interval 0.15 to 2.40). That is statistically significant, but the range is wide. The lower end is close to no effect. The authors also report substantial heterogeneity, meaning the trials differed a lot from one another in their results. This is a modest average, not a promise for any one person. The result held up in a check that removed trials with moderate or high risk of bias. Four trials remained and the gain was 1.39 points, though the confidence interval again came close to zero (0.03 to 2.75) and the differences between trials were even larger. The authors say the evidence was strongest for global cognition, memory and executive function. They say benefits were seen more consistently in cognitively healthy older adults and those with mild cognitive impairment. What does this mean for someone considering a supplement? The review does not show that any particular product works. The trials used very different bacteria, from single strains to a mix of 18, and doses ranging from 10 million to 50 billion live organisms. The studies were small and short. The review cannot say whether effects last beyond a few months, or whether a few points on a test make a difference in daily life. It also cannot show how the supplements might act on the brain. This is where the argument is weakest: the one pooled result rests on six trials that disagree with each other, and its lower bound is barely above zero. The authors themselves describe the evidence as positive but limited by the small number of high-quality studies. Their conclusion that gut modulation "holds huge promise" is stronger than the data alone firmly support. The TwinsUK press release THE ARISING · OCTOBER 18, 2026 PAGE 12 is more measured. It quotes Ni Lochlainn as saying the findings suggest the approach "could be a promising approach to supporting cognitive health in older adults," while stressing that "more high-quality research is needed." The practical reading is simple. These products are low risk and widely available, according to the authors, and the average signal is small but positive. No one should start or stop any supplement or medication without first talking to their clinician. What to watch next: larger, well-designed trials that test specific products at set doses over longer periods, to show which ones work and for whom. Sources: Age and ageing (2026), TwinsUK / King's College London (Age and Ageing) THE ARISING · OCTOBER 18, 2026 PAGE 13

THE ARISING · LONGEVITY & HEALTHSPAN SUNDAY, OCTOBER 18, 2026 IN THIS EDITION · LONGEVITY & HEALTHSPAN 1 ACOG Now Recommends Hormone Therapy for Many Women With Hot Flashes 2 Cardiologists Urge Doctors to Prescribe Exercise as Routine Heart Care 3 Fasting and Autophagy in Humans: Summary Calls Link Unproven 4 Gut Supplements May Modestly Improve Cognition in Adults Over 60, Review Finds 5 Higher Ultra-Processed Food Intake Linked to Silent Brain Damage on MRI 6 Higher VO2 Max Linked to Lower Depression and Anxiety Risk in UK Biobank 7 Bonn Lab Study Shows Blood Cells From Older Donors Lose Epigenetic Age in a Dish 8 Longer Sleep Linked to Kidney Disease Risk in Type 2 Diabetes LONGEVITY & HEALTHSPAN · WEEKLY READ · 2 MIN JAMA NETWORK OPEN · 2 SOURCES Higher Ultra-Processed Food Intake Linked to Silent Brain Damage on MRI Middle-aged adults who ate the most ultra-processed food were more likely to show small, symptom-free signs of blood vessel injury in the brain on MRI, according to a study in JAMA Network Open, yet they did not score worse on two common thinking tests. his is an observational, cross-sectional study. It included 8,783 Canadian adults aged 35 to 69 with no cardiovascular disease. Their average age wasT 57.7 years, and 4,917 (56.6%) were women. Because diet and health were looked at together, the study can show an association. It cannot show that the food caused the brain changes. Participants came from two Canadian research projects, the Canadian Alliance for Healthy Hearts and Healthy Minds and the Prospective Urban and Rural Epidemiology-MIND study. Intake of ultra-processed food was measured with food frequency questionnaires that have been validated before. Results were expressed as servings per 2,000 calories a day. The researchers compared the highest quarter of eaters with the lowest quarter. THE ARISING · OCTOBER 18, 2026 PAGE 14 The brain finding is the headline. The study defined vascular brain injury as either covert brain infarcts or high white matter hyperintensities. Covert infarcts are small areas of damage from interrupted blood flow that cause no obvious symptoms. White matter hyperintensities are bright spots on MRI in the brain's wiring. The highest quarter of ultra-processed food intake had higher odds of this injury than the lowest quarter (adjusted odds ratio 1.40; 95% confidence interval 1.10 to 1.77; P for trend = .009). An odds ratio is not the same as a 40% higher chance of damage, but it points in the same direction. The highest-intake group also carried more body fat. Body fat percentage was 1.7 percentage points higher, and visceral fat volume, the fat deep in the abdomen, was 5.7 mL greater. Liver fat did not differ significantly. Thinking performance did not follow the same pattern. The study found no significant associations between ultra-processed food intake and scores on the Montreal Cognitive Assessment or the Digital Symbol Substitution Test. The authors also say the link with brain injury was sensitive to how ultra-processed food was defined. That suggests the result depends on the measuring method and should be read with some caution. Many readers will want to know what this means for women. The abstract reports results for the whole group and does not break them out by sex, so this article cannot say whether the link is stronger in women. The study did include more women than men. The result adds to, but is not the same as, our October 11 report on a randomized trial in Nature Metabolism. That trial looked at how single meals affect the body. This study looks at usual eating habits and brain scans in thousands of people. Together they point to ultra-processed food as worth watching, but neither shows that cutting it back protects the brain. That has not been tested here. WHAT TO WATCH NEXT The authors say longitudinal studies, which follow people over time, are needed to establish whether the diet comes before the brain changes. Sources: JAMA Network Open (2026), Medical Xpress (reporting on JAMA Network Open, McMaster University) THE ARISING · OCTOBER 18, 2026 PAGE 15

THE ARISING · LONGEVITY & HEALTHSPAN SUNDAY, OCTOBER 18, 2026 IN THIS EDITION · LONGEVITY & HEALTHSPAN 1 ACOG Now Recommends Hormone Therapy for Many Women With Hot Flashes 2 Cardiologists Urge Doctors to Prescribe Exercise as Routine Heart Care 3 Fasting and Autophagy in Humans: Summary Calls Link Unproven 4 Gut Supplements May Modestly Improve Cognition in Adults Over 60, Review Finds 5 Higher Ultra-Processed Food Intake Linked to Silent Brain Damage on MRI 6 Higher VO2 Max Linked to Lower Depression and Anxiety Risk in UK Biobank 7 Bonn Lab Study Shows Blood Cells From Older Donors Lose Epigenetic Age in a Dish 8 Longer Sleep Linked to Kidney Disease Risk in Type 2 Diabetes LONGEVITY & HEALTHSPAN · WEEKLY READ · 2 MIN JOURNAL OF AFFECTIVE DISORDERS · 2 SOURCES Higher VO2 Max Linked to Lower Depression and Anxiety Risk in UK Biobank Adults with higher aerobic fitness were less likely to be diagnosed with depression or anxiety over the following 12 years, according to a large study in the Journal of Affective Disorders. his is an observational study in people. It followed 46,062 UK Biobank participants who had no depression or anxiety at the start. ObservationalT work can show that two things go together. It cannot show that one causes the other. Fitness was measured as VO2 max, the most oxygen a body can use during hard exercise. It is a standard marker of heart and lung fitness. Here it was estimated from a standardized submaximal exercise test, meaning participants were not pushed to their limit. The researchers, led by Liu Y, tracked new cases of depression and anxiety through linked health records coded with ICD-10, a standard system for recording diagnoses. THE ARISING · OCTOBER 18, 2026 PAGE 16 Over a median follow-up of 12.6 years, there were 2,190 cases of depression and 2,483 cases of anxiety. Compared with the least fit quarter of participants, the fittest quarter had a 24% lower risk of depression (hazard ratio 0.76, 95% confidence interval 0.64–0.91). Their anxiety risk was 17% lower (hazard ratio 0.83, 95% confidence interval 0.71–0.98). These results account for sociodemographic, lifestyle and clinical factors. The pattern also held across the fitness range. For each 1-standard-deviation increase in VO2 max, depression risk was 10% lower (0.90, 0.84–0.96). Anxiety risk was 6% lower (0.94, 0.88–1.00), a result right at the edge of statistical significance. The authors report a straight-line relationship for depression. For anxiety the relationship was nonlinear, so the benefit did not rise in a steady line. The study also reports that associations were stronger among people with a lower biological age. The abstract does not say how biological age was calculated, so that finding is hard to interpret here. The team also looked at blood proteins in a subset of 3,245 participants. They found seven plasma proteins that differed with fitness. Leptin and FABP4 were lower, and SPINT3 and INSL3 were higher. Several of these proteins were independently linked to mental health outcomes. The authors say this points to metabolic and neuroprotective pathways as possible explanations. That is a hypothesis, not a demonstrated mechanism. FOR YOU What does this mean for personal health? Aerobic fitness is already tied to heart health. This study adds that it may also go with a lower chance of common mental health diagnoses. But fitter people may differ from less fit people in ways that statistics cannot fully remove. Early, undiagnosed low mood could also make exercise harder. The abstract does not say how the authors handled that. And because outcomes came from health records, people with symptoms who never sought care would not be counted. The findings sit alongside another recent Arising report, on a separate UK Biobank study linking more REM sleep to lower risk of 83 diseases. Both are observational and both point to modifiable habits. Neither shows that changing the habit changes the outcome. THE ARISING · OCTOBER 18, 2026 PAGE 17 To watch next: randomized trials that assign people to supervised aerobic training and track depression and anxiety diagnoses over time, which would test whether fitness itself makes the difference. Sources: Journal of affective disorders (2026), Medscape (reporting on Journal of Affective Disorders) THE ARISING · OCTOBER 18, 2026 PAGE 18