Alzheimer's & other dementias
Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), involving 230 cognitively normal individuals and 394 individuals with diagnosed with MCI on the basis of one episodic test, has found that performance on two tests markedly improved the identification of those whose MCI was more serious.
MCI can be a step on the road to Alzheimer's, but it can also be a reversible condition, and it’s obviously helpful to be able to distinguish the two.
The study compared those with MCI whose memory performance was impaired only in one (story recall) or two (story recall and word list recall) tests. Those who performed poorly in both showed Alzheimer's biomarkers in the cerebrospinal fluid that more closely resembled Alzheimer's patients than those who only did poorly in one test. Moreover, they showed faster brain atrophy in the medial temporal lobes.
Alzheimer's disease was diagnosed within the three-year study period in around half of the participants who performed poorly in both tests, but in only 16% of those with a poor performance on one test.
An Argentinian study involving 1,414 adults with high blood pressure has concluded that the clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure
A higher prevalence of cognitive impairment was found with the clock drawing test (36%) compared to the MMSE (21%). Three out ten patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle aged patients.
The clock drawing test is particularly useful for evaluating executive functions, which are the cognitive function most likely to be damaged by untreated high blood pressure.
The clock drawing test involves being given a piece of paper with a 10 cm diameter circle on it, and having to write the numbers of the clock in the correct position inside the circle and then draw hands on the clock indicating the time "twenty to four".
The average blood pressure was 144/84 mmHg, average age was 60 years, and 62% were women.
The findings were presented at ESC Congress 2018.
Those suspected of cognitive impairment often undergo repeated cognitive testing over time — indeed it is the change over time that is most diagnostic. However, most cognitive functions get better with practice. A new study involving 995 middle- to late-middle-aged men has found that, indeed, there were significant practice effects in most cognitive domains, and diagnoses of MCI doubled from 4.5 to 9% after correcting for practice effects.
A large study involving 1820 adults (44+), of whom 568 were cognitively healthy, 885 had MCI, and 367 mild Alzheimer's, found that verb fluency worsened at each stage of cognitive decline, and worse scores in verb fluency task were significantly related to development of MCI, and progression from MCI to dementia. Worsening verb fluency was also associated with a faster decline to MCI, but not to faster progression from MCI to dementia.
Most previous research with word fluency has used category and letter fluency tasks (which demand generating names) rather than verb fluency, but verb fluency is more cognitively demanding than generating names, and may thus be a more sensitive tool.
A brief, simple number naming test has been found to differentiate between cognitively healthy older adults and those with MCI or Alzheimer's.
The King-Devick (K-D) test is a one- to two-minute rapid number naming test that has previously been found useful in the detection of concussion, as well as in detecting level of impairment in other neurological conditions such as Parkinson's disease and multiple sclerosis. The K-D test can be quickly administered by non-professional office staff on either a tablet (iPad) or in a paper version.
The test accurately distinguished the controls from the cognitively impaired individuals more than 90% of the time.
The study involved 206 older adults, including 135 cognitively healthy individuals, 39 people with MCI, and 32 Alzheimer's patients.
The test will need to be validated in larger samples.
A number of studies have shown that people’s own subjective impressions of memory problems should not be discounted, but they shouldn’t be given too much weight either, since many people are over-anxious nowadays about their prospects of dementia. But there is a further complication to this issue, which is that being unaware of one’s own memory problems is typical of Alzheimer's.
Anosognosia is the name for this condition of not being able to recognize one’s memory problems.
A study involving 450 patients who experienced mild memory deficits, but were still capable of taking care of themselves, assessed this awareness by asking both the patients and their close relatives about the patient’s cognitive abilities. Anosognosia was diagnosed when a patient reported having no cognitive problems but the family member reported significant difficulties.
The study found that those suffering from anosognosia had impaired brain metabolic function and higher rates of amyloid deposition. Two years later, they were more likely to have developed dementia.
A study involving 1,062 older adults (55-90), including 191 people with Alzheimer's disease, 499 with MCI and 372 healthy controls, found that those with anosognosia had reduced glucose uptake in specific brain regions. Glucose uptake is impaired in Alzheimer's disease.
The hippocampus, one of the earliest brain regions affected in Alzheimer's, has a number of important memory functions. One of these is relational memory — the hippocampus can bind together pieces of information stored in different parts of the brain, so that, for example, you can remember the name when you see the associated face.
A new cognitive test that assesses relational memory has been found to be effective in distinguishing cognitive impairment that reflects very early mild Alzheimer's from normal aging.
The test involves a circle divided into three parts, each having a unique design. After studying a circle, participants needed to pick its exact match from a series of 10 circles, presented one at a time.
People with very mild Alzheimer's disease did worse overall on the task than those in the healthy aging group, who, in turn, did worse than a group of young adults. Moreover, those with Alzheimer's were particularly susceptible to interference from intervening lure stimuli. Including this in the analysis improved the test’s ability to differentiate between those who did and those who did not have Alzheimer's. It also provides evidence that Alzheimer's is qualitatively different from normal age-related cognitive decline, not simply an extension of it.
The study involved 90 participants, including 30 young adults, 30 cognitively healthy older adults, and 30 with very early Alzheimer's.
 Vuoksimaa, E., McEvoy L. K., Holland D., Franz C. E., Kremen W. S., & Initiative for. the Alzhei
(2018). Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer’s disease.
Brain Imaging and Behavior.
 Elman, J. A., Jak A. J., Panizzon M. S., Tu X. M., Chen T., Reynolds C. A., et al.
(2018). Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 10, 372 - 381.
Alegret M, Peretó M, Pérez A, Valero S, Espinosa A, Ortega G, Hernández I, Mauleón A, Rosende-Roca M, Vargas L, Rodríguez-Gómez O, Abdelnour C, Berthier ML, Bak TH, Ruiz A, Tárraga L, Boada M. The Role of Verb Fluency in the Detection of Early Cognitive Impairment in Alzheimer's Disease Journal of Alzheimer's Disease 2018.
 Galetta, K. M., Chapman K. R., Essis M. D., Alosco M. L., Gillard D., Steinberg E., et al.
(2017). Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia.
Alzheimer Disease & Associated Disorders. 31(2), 152.
 Therriault, J., Ng K. Pin, Pascoal T. A., Mathotaarachchi S., Kang M. Su, Struyfs H., et al.
(2018). Anosognosia predicts default mode network hypometabolism and clinical progression to dementia.
Neurology. 90(11), e932.
 Gerretsen, P., Chung J. Ku, Shah P., Plitman E., Iwata Y., Caravaggio F., et al.
(2017). Anosognosia Is an Independent Predictor of Conversion From Mild Cognitive Impairment to Alzheimer’s Disease and Is Associated With Reduced Brain Metabolism.
The Journal of Clinical Psychiatry. 78(9), 1187 - 1196.
Monti, J. M., Balota, D. A., Warren, D. E., & Cohen, N. J. (2014). Very mild Alzheimer׳s disease is characterized by increased sensitivity to mnemonic interference. Neuropsychologia, 59, 47–56. https://doi.org/10.1016/j.neuropsychologia.2014.04.007
Data from the Harvard Aging Brain Study found that higher amyloid beta levels were associated with increasing anxiety symptoms in cognitively normal older adults. The results suggest that worsening anxious-depressive symptoms may be an early predictor of elevated amyloid beta levels.
The study involved 270 cognitively healthy older adults (62-90). For five years, participants were annually assessed for depression, apathy-anhedonia, dysphoria, and anxiety.
Donovan et al. 2017. Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults. The American Journal of Psychiatry DOI: 10.1176/appi.ajp.2017.17040442
A study has shown new technology can quickly and non-invasively detect reduced blood capillaries in the back of the eye that are an early indication of Alzheimer's. It also shows that these signs can help distinguish between Alzheimer's and MCI.
The study compared the retinas of 39 Alzheimer's patients, 37 people with MCI, and 133 cognitively healthy people. The Alzheimer's group had loss of small retinal blood vessels at the back of the eye and a specific layer of the retina was thinner when compared to people with MCI and healthy people. The differences in density were statistically significant after researchers controlled for factors including age and sex.
It's been known that patients with Alzheimer's had decreased retinal blood flow and vessel density but it had not been known if these changes were also present in individuals with early Alzheimer's or aMCI.
Larger datasets are required to validate the marker.
 Zhang, Y. Stephanie, Zhou N., Knoll B. Marie, Samra S., Ward M. R., Weintraub S., et al.
(2019). Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer’s Disease on optical coherence tomography angiography.
PLOS ONE. 14(4), e0214685.
A very long-running study involving 290 people at risk of Alzheimer's has found that, in those 81 people who developed MCI or dementia, subtle changes in cognitive test scores were evident 11 to 15 years before the onset of clear cognitive impairment. They also showed increases in the rate of change of tau protein in cerebrospinal fluid an average of 34.4 years (for t-tau, or total Tau) and 13 years (for a modified version called p-tau) before the beginning of cognitive impairment.
 Younes, L., Albert M., Moghekar A., Soldan A., Pettigrew C., & Miller M. I.
(2019). Identifying Changepoints in Biomarkers During the Preclinical Phase of Alzheimer’s Disease.
Frontiers in Aging Neuroscience. 11,
A long-term study of nearly 3,000 older adults (57-85) has found that those who couldn’t identify at least four out of five common odors were more than twice as likely as those with a normal sense of smell to develop dementia within five years.
Of the participants, some 14% could name just three out of five, 5% could identify only two scents, 2% just one, and 1% couldn’t identify a single smell.
Five years after the smell test, almost all of the study subjects who were unable to name a single scent had been diagnosed with dementia, and nearly 80% of those who provided only one or two correct answers.
The test involved a well-validated tool known as "Sniffin'Sticks." The five odors, in order of increasing difficulty, are peppermint, fish, orange, rose and leather.
A study involving nearly 300 older adults (average age 63) who had a parent with Alzheimer’s has found that those with the most difficulty in identifying odors were those in whom Alzheimer's biomarkers were most evident.
Sense of smell was assessed using multiple choice scratch-and-sniff tests to identify scents as varied as bubble gum, gasoline or the smell of a lemon. A hundred of the participants had regular lumbar punctures to measure the Alzheimer's biomarkers in the cerebrospinal fluid.
A seven-year study involving a multi-ethnic (34% White, 30% African-American, 36% Hispanic) sample of 757 healthy older adults (average age 80.7) found that lower odor identification scores on UPSIT were significantly associated with both the transition to dementia and cognitive decline.
For each point lower that a person scored on the UPSIT, the risk of Alzheimer's increased by about 10%.
The report was reported at the Alzheimer's Association International Conference® 2014 in Copenhagen
An animal study has shown that olfactory dysfunction occurs much earlier than cognitive dysfunction, and that this is related to the amyloid-beta protein. Although it’s been thought that this protein is expressed only in the central nervous system, the study detected direct expression of the protein in the olfactory epithelium, part of the peripheral nervous system. Moreover, the amyloid-beta protein had a fatal effect on olfactory nerve cells in the olfactory epithelium and directly induced the failure of olfactory function.
A less alarming explanation for why our sense of smell tends to decline in old age comes from a mouse study that found that fewer stem cells become olfactory cells in old age as they tend to remain in the stem cell pool and become less active.
Following on from a previous study in which more than 2,200 older adults (71-82) undertook smell identification tests, investigation 13 years later found that a poor sense of smell was linked to a 46% greater risk of dying within 10 years compared with those ranked as having a good sense of smell. Poor sense of smell was particularly linked to death from dementia and Parkinson’s disease, with some signs that poor smell might also be linked to death from cardiovascular disease. There was no link between poor sense of smell and death from cancer or respiratory diseases. 22% of the overall increased risk of death among those with a poorer sense of smell was down to neurodegenerative diseases.
The link was only present among those who were in very good health at the start of the study.
 Adams, D. R., Kern D. W., Wroblewski K. E., McClintock M. K., Dale W., & Pinto J. M.
(2018). Olfactory Dysfunction Predicts Subsequent Dementia in Older U.S. Adults.
Journal of the American Geriatrics Society. 66(1), 140 - 144.
 Lafaille-Magnan, M-E., Poirier J., Etienne P., Tremblay-Mercier J., Frenette J., Rosa-Neto P., et al.
(2017). Odor identification as a biomarker of preclinical AD in older adults at risk.
Neurology. 89(4), 327.
 Yoo, S-J., Lee J-H., Kim S. Yeun, Son G., Kim J. Yeon, Cho B., et al.
(2017). Differential spatial expression of peripheral olfactory neuron-derived BACE1 induces olfactory impairment by region-specific accumulation of β -amyloid oligomer.
Cell Death & Disease. 8(8), e2977 - e2977.
 Liu, B., Luo Z., Pinto J. M., Shiroma E. J., Tranah G. J., Wirdefeldt K., et al.
(2019). Relationship Between Poor Olfaction and Mortality Among Community-Dwelling Older Adults: A Cohort Study.
Annals of Internal Medicine. 170(10), 673.
 Bast, L., Calzolari F., Strasser M. K., Hasenauer J., Theis F. J., Ninkovic J., et al.
(2018). Increasing Neural Stem Cell Division Asymmetry and Quiescence Are Predicted to Contribute to the Age-Related Decline in Neurogenesis.
Cell Reports. 25(12), 3231 - 3240.e8.
Alzheimer's disease is associated with abnormalities in the vast network of blood vessels in the brain, but it hasn’t been known how this affects cognition. A study has now shown that a blood-clotting protein called fibrinogen plays a part.
The study found that fibrinogen, after leaking from the blood into the brain, activates the brain's immune cells and triggers them to destroy synapses, which are critical for neuronal communication.
Loss of synapses is known to cause memory loss, and the study found that preventing fibrinogen from activating the brain's immune cells protected Alzheimer's mice from memory loss.
Moreover, fibrinogen had this effect even in brains that lack amyloid plaques.
The findings help explain how elderly people with vascular pathology could show similar rates of cognitive decline as age-matched people with amyloid pathology. The same human studies also found that those with both types of pathology had much worse and more rapid cognitive decline.
Another study suggests that nearly half of all dementias, including Alzheimer's, begins with the breakdown of the smallest blood vessels in the brain and the "gatekeeper cells" that surround and protect the capilleries.
The collapse of pericytes (the gatekeeper cells) reduces myelin and white matter structure in the brain. They do this via fibrinogen. Fibrinogen develops blood clots so wounds can heal but when the gatekeeper cells fail, too much fibrinogen enters the brain and causes white matter to die.
Mouse studies showed that controlling fibrinogen levels can reverse or slow white matter disease.
Postmortem study of human brains found that Alzheimer’s brains had about 50% fewer gatekeeper cells and three times more fibrinogen proteins in watershed white matter areas, compared to healthy brains.
The mouse study found that white matter changes in mice began as early as 12 to 16 weeks old, the equivalent of 40 years in humans.
When an enzyme known to reduce fibrinogen was introduced into the mice, white matter volume returned to 90% of their normal state, and white matter connections were back to 80% productivity.
 Merlini, M., Rafalski V. A., Coronado P. E. Rios, T. Gill M., Ellisman M., Muthukumar G., et al.
(2019). Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model.
Neuron. 101(6), 1099 - 1108.e6.
 Montagne, A., Nikolakopoulou A. M., Zhao Z., Sagare A. P., Si G., Lazic D., et al.
(2018). Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.
Nature Medicine. 24(3), 326 - 337.
It’s been known that decreased blood flow in the brain occurs in people with Alzheimer's, and recent studies suggest that brain blood flow deficits are one of the earliest detectable symptoms of dementia. A study has now shown why it occurs: a small percentage of capillaries, the smallest blood vessels in the brain, are blocked by white blood cells stuck to the inside of the capillaries.
Recent research has shown that capilleries are vital for monitoring and directing blood flow around the brain.
 Hernández, J. C. Cruz, Bracko O., Kersbergen C. J., Muse V., Haft-Javaherian M., Berg M., et al.
(2019). Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models.
Nature Neuroscience. 22(3), 413 - 420.
New findings identify a mechanism that accelerates aging in the brain and gives rise to Alzheimer's disease.
The findings center on “enhancers”, which turn the activity of genes up or down based on influences like aging and environmental factors. Comparing enhancers in brain cells of people at varying stages of Alzheimer's and healthy people has revealed that in normal aging, there is a progressive loss of important epigenetic marks on enhancers. This loss is accelerated in the brains of people with Alzheimer's.
These enhancers also over-activate a suite of genes involved in Alzheimer's pathology, spurring the formation of plaques and tangles, and reactivating the cell cycle in fully formed cells — a highly toxic combination.
The study also links enhancer changes to the rate of cognitive decline in Alzheimer's patients.
 Li, P., Marshall L., Oh G., Jakubowski J. L., Groot D., He Y., et al.
(2019). Epigenetic dysregulation of enhancers in neurons is associated with Alzheimer’s disease pathology and cognitive symptoms.
Nature Communications. 10(1), 1 - 14.
A mouse study has shown that, as cells age, their ability to remove damaged proteins and structures declines.
The process of waste management, called autophagy, involves a component within the cell (an autophagosome) engulfing misfolded proteins or damaged structures (putting them in a garbage bag, essentially). The autophagosome then fuses with a second cellular structure, called a lysosome, that contains the enzymes needed to breakdown the garbage, allowing the components to be recycled and reused.
It’s thought that this decline in autophagy makes neurons more vulnerable to genetic or environmental risks.
The mouse study found that aging brought a significant decrease in the number of autophagosomes produced, along with pronounced defects in their structure.
However, activating the protein WIPI2B restored autophagosome formation.
A cleaning process in brain cells called mitophagy breaks down defective mitochondria and reuses the proteins that they consist of. When the process breaks down, defective mitochondria accumulate in brain cells.
Research has now found that this is markedly present in cells from both humans and animals with Alzheimer's. Moreover, when active substances targeted at the cleaning process were tried in live animals, their Alzheimer's symptoms almost disappeared.
A 2015 study found how toxic tau fibrils spread during the early stages of Alzheimer's disease. Apparently the fibrils (accumulations of tau proteins) can be carried from one neuron to another by microglia.
Microglia act as the brain's immune cells, in which role they identify and clear damage and infection. They clear damage by first engulfing dead cells, debris, inactive synapses or even unhealthy neurons, then releasing nano-scale particles called exosomes, which can be absorbed by other cells.
It used to be thought that exosomes simply help the cell to get rid of waste products. It now appears that cells throughout the body use exosomes to transmit information. This requires them to contain both proteins and genetic material, which other cells can absorb. Hence their ability to spread tau protein, and hence, it now seems, their ability to also transport amyloid-beta.
Amyloid plaques and tau tangles are key biomarkers for Alzheimer’s, but research indicates that it is the tau tangles that are the real problem — the main problem with amyloid plaques is that they lead to tau tangles. A new study indicates how that happens.
A mouse study modified the TREM2 genes, which affect the health of microglia. So some mice carried the common variant of the gene, meaning that their microglia were fully functional, and some carried the risky variant, or no gene at all.
When seeded with tau protein from Alzheimer’s patients, those brains with weakened microglia produced more tau tangle-like structures near the amyloid plaques than in mice with functional microglia.
It was also revealed that microglia normally form a cap over amyloid plaques that limits their toxicity to nearby neurons. When the microglia failed to do that, neurons suffered more damage, creating an environment that fostered the formation of tau tangle-like lesions.
The findings were supported by the finding that humans with TREM2 mutations who died with Alzheimer’s had more tau tangle-like structures near their amyloid plaques than people who died with Alzheimer’s but didn’t have the risky gene.
However, it should be noted that in more advanced stages of Alzheimer’s, mice with the common TREM2 variant showed faster plaque growth. This appears to be linked to the gene inducing microglia to produce ApoE, which enhances aggregate formation.
The finding adds to evidence that Alzheimer's treatment has to take into account the stage at which the disease is at.
Another study that modified the TREM2 gene in mice found that the difference between those with the gene and those without was not in the amount of tau tangles, but rather in the way their immune cells responded to the tau tangles. The microglia in mice with TREM2 were active, releasing compounds that in some circumstances help fight disease, but in this case primarily injured and killed nearby neurons. The microglia in mice without TREM2 were much less active, and their neurons were relatively spared.
A study found that, if the gene for the TDP-43 protein was turned off in microglia, its activity increased, and amyloid-beta was removed very efficiently. However, when TDP-43 was switched off in microglia in mice, it didn’t just get better at removing amyloid-beta, but also led to a significant loss of synapses.
Clearly, dysfunction of microglia is a complicated business, and it’s suggested that such dysfunction may be one reason why many Alzheimer's medications reduce amyloid plaques but fail to improve cognition.
Microglia come in many forms. A survey of brain microglia has classified microglia into at least nine distinct groups, including some types never detected in the past. Some types appeared almost exclusively in the embryonic or newborn stages, others only after injury.
One group tended to cluster near the brain's developing white matter. Another appears to be very inflammatory compared with other microglia, and has been found in people with MS.
Microglia were most diverse early in brain development, in the aged brain and in disease.
 Stavoe, A. K. H., Gopal P. P., Gubas A., Tooze S. A., & Holzbaur E. L. F.
(2019). Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons.
(Dikic, I., Marder E., & Hurley J. H., Ed.).eLife. 8, e44219.
 Fang, E. F., Hou Y., Palikaras K., Adriaanse B. A., Kerr J. S., Yang B., et al.
(2019). Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease.
Nature Neuroscience. 22(3), 401 - 412.
Maitrayee Sardar Sinha, Anna Ansell-Schultz, Livia Civitelli, Camilla Hildesjö, Max Larsson, Lars Lannfelt, Martin Ingelsson and Martin Hallbeck, Alzheimer disease pathology propagation by exosomes containing toxic amyloid-beta oligomers, Acta Neuropathologica, published online 13 June 2018, doi: 10.1007/s00401-018-1868-1 https://link.springer.com/article/10.1007/s00401-018-1868-1
 Leyns, C. E. G., Gratuze M., Narasimhan S., Jain N., Koscal L. J., Jiang H., et al.
(2019). TREM2 function impedes tau seeding in neuritic plaques.
Nature Neuroscience. 22(8), 1217 - 1222.
Parhizkar et al. (2019): "Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE", Nature Neuroscience, DOI: 10.1038/s41593-018-0296-9
Leyns C, Ulrich J, Finn M, Stewart F, Koscal L, Remolina Serrano J, Robinson G, Anderson E, Colonna M, Holtzman DM. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proceedings of the National Academy of Sciences. Week of Oct. 9, 2017.
 Paolicelli, R. C., Jawaid A., Henstridge C. M., Valeri A., Merlini M., Robinson J. L., et al.
(2017). TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss.
Neuron. 95(2), 297 - 308.e6.
 Hammond, T. R., Dufort C., Dissing-Olesen L., Giera S., Young A., Wysoker A., et al.
(2019). Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes.
Immunity. 50(1), 253 - 271.e6.
Data from the Framingham Heart Study has found carriers of the ApoE4 gene were much more likely to develop Alzheimer’s if they also had chronic low-grade inflammation. Indeed, the researchers suggest that, in the absence of inflammation, there might be no difference of Alzheimer's risk between ApoE4 and non-ApoE4 carriers.
Data from 1,532 participants in a long-running study, in which participants were tested five times every 3 years (on average), found that those who showed increasing inflammation had greater abnormalities in the brain's white matter structure.
90 people transitioned from low to persistently elevated C-reactive protein during midlife, indicating increasing inflammation. Their brains appear similar to that of a person 16 years older, researchers estimate.
Common causes of chronic inflammation include cardiovascular disease, heart failure, diabetes, high blood pressure and infections such as hepatitis C or HIV.
61% of participants were women, and 28% were African-American. At the final visit, participants were an average age of 76.
 Tao, Q., Ang T. Fang Alvin, DeCarli C., Auerbach S. H., Devine S., Stein T. D., et al.
(2018). Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 CarriersChronic Low-grade Inflammation and Risk of Alzheimer Disease in ApoE4 CarriersChronic Low-grade Inflammation and Risk of Alzheimer Disease in ApoE4 Carriers.
JAMA Network Open. 1(6), e183597 - e183597.
 Walker, K. A., B. Windham G., Power M. C., Hoogeveen R. C., Folsom A. R., Ballantyne C. M., et al.
(2018). The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study.
Neurobiology of Aging. 68, 26 - 33.
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