News & Publications

• Low bone density may increase dementia risk. www.medscape.com
  Nutrition Brain Aging Dementia Bone Small Vessel Disease

  A new study shows that having low bone density may increase a person’s risk for cerebral small vessel disease – a driver of dementia. People with the lowest bone density in their upper femur were twice as likely to develop dementia over a ten-year period than those with the highest bone density.

  Researchers categorized nearly 1,200 people over the age of 50 years according to their small vessel health status and bone density. They also measured serum bone turnover markers and microRNAs related to cerebral small vessel disease and bone metabolism.

  They found that cerebral small vessel disease scores increased as bone mineral density decreased. They also found that levels of microRNA-378f, a non-coding RNA molecule that inhibits bone formation, were higher among participants with low bone density.

  In older adults, dementia and low bone mineral density often coincide. In addition, physical inactivity and poor nutrition, common among people with dementia, can accelerate bone loss. Scientists don’t fully understand the extent to which bone loss is present before the onset of dementia, however. (Read more about bone health in the two reviews presented below.)

  The findings from this study suggest that bone and brain health are closely linked, possibly via a bone-brain axis that regulates brain health. However, whether bone loss causes cerebral small vessel disease and subsequent dementia remains unclear. The findings also highlight the importance of maintaining bone health throughout the lifespan. Learn how resistance exercise helps increase bone density in this clip featuring Dr. Brad Schoenfeld.

  • Read study abstract.
  • Read about cerebral small vessel disease in our overview article.
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• Air pollution may attenuate the beneficial association vigorous physical activity with low white-matter hyperintensity volume n.neurology.org
  Exercise Brain Aging Pollution Aerobic Neurodegeneration Small Vessel Disease

  Air pollution negates some of the beneficial effects of vigorous-intensity exercise.

  Components present in air pollution – a mixture of toxic chemicals, gases, and particulate matter – can cross biological barriers, including the blood-brain barrier. Exposure to air pollutants is associated with poor health outcomes and an increased risk for both acute and chronic diseases. A recent study suggests that air pollution negates some, but not all, of the beneficial effects of vigorous-intensity aerobic exercise.

  Robust evidence demonstrates that vigorous-intensity aerobic exercise (defined as activity that achieves a heart rate that is 70 to 80 percent of one’s maximum) benefits brain health. For example, vigorous-intensity aerobic exercise appears to activate the endocannabinoid system to promote motor sequence memory and learning. Other evidence suggests it improves mood.

  The study involved 8,600 adult participants enrolled in the UK Biobank study. Participants wore wrist accelerometers to track their physical activity. They also underwent magnetic resonance imaging (MRI) to assess their structural brain volumes and identify the presence of white matter hyperintensities – areas of the brain that show up as distinct white areas on MRIs and indicate cerebral small blood vessel disease. The investigators estimated the participants' exposure to air pollution based on where the participants lived.

  The investigators found that the more physically active participants were, the less their brains showed evidence of shrinkage, and the fewer white matter hyperintensities they exhibited – an effect roughly equivalent to being three years younger. Participants who were exposed to more air pollution exhibited greater brain shrinkage than those with less exposure – about the amount observed in one year of normal aging. However, participants who exercised the most and had the most exposure to air pollution demonstrated no evidence of more brain shrinkage, but they exhibited more white matter hyperintensities, especially if they engaged in vigorous-intensity aerobic exercise.

  These findings support earlier studies that demonstrate the beneficial health effects of vigorous-intensity exercise on the brain but suggest that exercising in areas where air pollution is high negates some of these benefits. The authors recommended that because most air pollution comes from vehicle exhaust, people should exercise in areas far from heavily trafficked roads.

  • View study abstract.

  • Read about the many beneficial health effects of aerobic exercise in our overview article.

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• Periodontal Condition Is Correlated with Deep and Subcortical White Matter Hyperintensity Lesions in Japanese Adults www.mdpi.com
  Brain Aging Inflammation Small Vessel Disease

  Gum disease may increase the risk of white matter hyperintensities, a type of brain lesion.

  White matter hyperintensities are brain lesions that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. High blood pressure is the primary contributor to white matter hyperintensity formation, but other factors likely play roles, as well. Findings from a 2020 study suggest that periodontitis is associated with white matter hyperintensities.

  Periodontitis is a chronic inflammatory condition of the gums, characterized by red, tender, swollen, or bleeding gums. It is typically caused by poor oral hygiene and is more common with age, manifesting in more than two-thirds of adults over the age of 65 years. Periodontitis is diagnosed using a periodontal probe, which is used to assess the depth of pockets in the gum. In a healthy mouth, a pocket can be anywhere from 1 to 3 millimeters deep. Deeper pockets are indicators of gum inflammation and disease.

  The study involved more than 400 adults (average age, 54 years) who underwent a routine dental exam that included pocket depth probing. The investigators performed MRI scans on the participants to identify the presence of white matter hyperintensities, which were classified according to their size, number, and severity. They gathered information about the participants' general health and lifestyles and measured their C-reactive protein (CRP, a biomarker of inflammation). They found that nearly half of the participants had white matter hyperintensities. Those who did were nearly three times more likely to be at least 65 years old, more than twice as likely to have elevated systolic blood pressure, and nearly twice as likely to have deeper pocket depth (6 millimeters or more). Having white matter hyperintensities was not associated with the participants' CRP levels.

  These findings suggest that older age, elevated blood pressure, and periodontitis are associated with an increased risk of developing white matter hyperintensities, but inflammation is not a driver of this association. Evidence indicates that white matter hyperintensities are predictive of the amount and degree of leakage of the blood-brain barrier leakage. Learn more in our overview article.

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• Systemic immune-inflammation index is associated with white matter hyperintensity volume: among cSVD pathologies, WMH may be more inflammation-related www.nature.com
  Brain Aging Inflammation Small Vessel Disease

  From the article:

  Systemic immune-inflammation index (SII) is a novel inflammatory marker based on the composition ratio of blood cell counts. In this study, we evaluated the association between the SII and cerebral small vessel disease (cSVD) in health check-up participants. We evaluated participants from our health check-up registry between 2006 and 2013. The SII was calculated using the following formula: SII = (platelet count × neutrophil count)/lymphocyte count. cSVD was assessed by considering white matter hyperintensity (WMH) volume, lacunes, and cerebral microbleeds (CMBs). A total of 3187 participants were assessed. In multivariable linear regression analysis, the SII was significantly related to WMH volume [β = 0.120, 95% confidence interval (CI) 0.050–0.189]. However, lacunes and CMBs showed no statistical significance with the SII. In the subgroup analysis by age, the SII was significantly associated with WMH volume only in participants aged ≥ 60 years (β = 0.225, 95% CI 0.068–0.381). In conclusion, a high SII was associated with cSVD. Since this association was more pronounced in WMH than in lacunes or CMBs, WMH might be closer to the inflammation-related pathological mechanisms.

  Age-related changes in systemic inflammation:

  Interestingly, the close association between the SII and WMH volume in our study was significant only in older participants aged ≥ 60 years. This might be related to the aging-related changes in the homeostatic maintenance of our body’s inflammation and immunity (e.g., inflammaging, immunosenescence, and homeostenosis)

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• Greater visceral and total body fat associated with vascular brain injury and impaired cognitive scores www.sciencedaily.com
  Brain Obesity Dementia Metabolic Syndrome Blood-Brain Barrier Small Vessel Disease Visceral Fat

  From the article:

  In the study, 9,166 participants were measured by bioelectrical impedance analysis to assess their total body fat.

  As well, 6,733 of the participants underwent magnetic resonance imaging (MRI) to measure abdominal fat packed around the organs known as visceral fat, and the MRI also assessed vascular brain injury – areas in the brain affected by reduced blood flow to the brain.

  […]

  Co-author Eric Smith, a neurologist, scientist and an associate professor of clinical neurosciences at the University of Calgary, said that “preserving cognitive function is one of the best ways to prevent dementia in old age. This study suggests that one of the ways that good nutrition and physical activity prevent dementia may be by maintaining healthy weight and body fat percentage.”

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• Four pathologies of SVD associate with dementia: white matter hyperintensities, cerebral microbleeds, lacunar infarcts, enlarged perivascular spaces www.sciencedaily.com
  Brain Dementia Cardiovascular Blood-Brain Barrier Small Vessel Disease

  The four pathologies that were detectable by MRI included:

  • moderate-to-severe white matter hyperintensities - blood pressure is a risk factor for this one
  • deep cerebral microbleeds
  • lacunar infarcts
  • enlarged perivascular space.

  From the article:

  The subjects were given cognitive tests and brain MRIs. The MRIs were examined for four main components of small vessel disease (SVD). These four components, which include evidence of microbleeds and minor strokes, then were added to create a total SVD score. The score ranges from zero points (no SVD) to 4 points (severe SVD).

  The study found that that 61 percent of the subjects had zero points on the total SVD score, 20 percent had 1 point, 12 percent had 2 points, 5 percent had 3 points and 2 percent had 4 points. The higher the SVD score, the greater the cognitive decline. Researchers also found that each individual component of SVD predicted cognitive decline as well as the total SVD score did.

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• Small-vessel disease could provoke amyloid pathology while Alzheimer's-associated cerebral amyloid pathology may lead to auxiliary vascular damage www.sciencedaily.com
  Brain Alzheimer's Cardiovascular Blood-Brain Barrier Small Vessel Disease

  Cerebral small vessel disease is associated with amyloid-beta deposition in the brain, especially among APOE4 carriers.

  Small vessel disease is a collection of conditions characterized by damage to arterioles and capillaries, resulting in reduced or interrupted blood flow to the affected organ. These conditions typically affect organs that receive substantial blood flow, such as the brain, kidney, and retina, and are principal drivers of chronic diseases such as strokes, renal failure, dementia, and blindness. Findings from a 2014 study suggest that people who have small vessel disease in the brain exhibit greater deposition of amyloid-beta plaques, especially if they are carriers of the APOE4 gene.

  Amyloid-beta is a toxic 42-amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta deposition is associated with Alzheimer’s disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia.

  APOE is a protein involved in lipid transport. A variant in the APOE gene, called apolipoprotein E4 (APOE4), is the major genetic risk factor for Alzheimer’s disease. Having one APOE4 allele increases a person’s Alzheimer’s disease risk as much as threefold; carrying two APOE4 alleles increases risk as much as 15-fold.

  The cross-sectional study included more than 900 patients enrolled in the Amsterdam Dementia Cohort study who had been diagnosed as having Alzheimer’s disease, vascular dementia, or self-reported memory complaints. The investigators analyzed the patients' cerebrospinal fluid for the presence of amyloid-beta and other markers of Alzheimer’s disease and genotyped the patients to assess APOE status.

  They also performed magnetic resonance imaging (MRI) of the patients' brains to identify the presence of white matter hyperintensities and microbleeds. White matter hyperintensities, areas in the brain that appear as intense white spots on MRIs, are often indicators of cerebral small vessel disease and are considered a risk factor for dementia. Microbleeds are small, chronic hemorrhages that are indicative of cerebral amyloid angiopathy, a condition in which amyloid-beta accumulates on the walls of brain arteries.

  They found that patients with Alzheimer’s disease had lower levels of amyloid-beta in their cerebrospinal fluid, an effect that was more pronounced among APOE4 carriers. Patients with low amyloid-beta levels in their cerebrospinal fluid were more likely to have white matter hyperintensities and microbleeds, indicating a direct relationship between a pathological hallmark of Alzheimer’s disease and small vessel disease.

  These findings suggest that Alzheimer’s disease and small vessel disease are intrinsically linked, especially among APOE4 carriers. [Learn more about small vessel disease in our overview article.](Coming soon)

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• Leaky blood-brain barrier caused by cerebral small vessel disease increases the prevalence of white-matter hyperintensities and brain damage www.sciencedaily.com
  Brain Aging Dementia Blood-Brain Barrier Small Vessel Disease

  Poor blood-brain barrier integrity drives white matter losses.

  White matter hyperintensities are areas in the brain that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. A 2021 study found that breaches in blood-brain barrier integrity are associated with brain tissue losses and precede the appearance of white matter hyperintensities.

  The blood-brain barrier, a specialized system of endothelial cells that shields the brain from toxins present in the blood, supplies the brain’s tissues with vital nutrients and substances necessary for neuronal and metabolic function. The structural integrity of the blood-brain barrier is therefore critical for homeostatic maintenance of the brain microenvironment.

  The study involved 43 patients (average age 58 years) who had been diagnosed with cerebral small vessel disease, as evidenced by having experienced a stroke or demonstrating mild cognitive impairment. At the beginning of the study and two years later, participants underwent a variety of MRI techniques that quantified their overall blood-brain barrier permeability as well as the areas surrounding white matter hyperintensities.

  The MRIs revealed that participants who had the greatest amount of leaky brain tissue at the beginning of the study exhibited greater white matter tissue losses two years later. These tissue losses translated to greater permeability, a phenomenon particularly evident in the areas surrounding the brain lesions associated with white matter hyperintensities.

  These findings suggest that losses in blood-brain barrier integrity damage brain tissue, driving increased permeability and white matter losses. In turn, these changes potentiate the disease processes associated with cerebral small vessel disease. Learn more about the blood-brain barrier in our overview article.

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