brain atrophy

Slower walking speeds linked to dementia risk

  • A large, long-running study has found older adults with a slower walking speed were more likely to develop dementia in the next decade.
  • Another long-running study has found that slowing over 14 years was linked to brain atrophy in the hippocampus, and cognitive impairment.

Data from the English Longitudinal Study of Aging, in which nearly 4,000 older adults (60+) had their walking speed assessed on two occasions in 2002-2003 and in 2004-2005, those with a slower walking speed were more likely to develop dementia in the next 10 years. Those who experienced a faster decline in walking speed over the two-year period were also more likely to develop dementia.

https://www.eurekalert.org/pub_releases/2018-03/ags-oaw032318.php

A long-running study involving 175 older adults (70-79) found that slowing in walking speed over a 14-year period was associated with cognitive impairment, and with shrinkage of the right hippocampus specifically.

Gait slowing over an extended period of time was a stronger predictor of cognitive decline than slowing at a single time point. All the participants slowed over time, but those who slowed by 0.1 seconds more per year than their peers were 47% more likely to develop cognitive impairment.

The finding held even when the researchers took into account slowing due to muscle weakness, knee pain and diseases, including diabetes, heart disease, and hypertension.

Typically, a slowing gait is seen as a physical issue, but doctors should consider that there may be a brain pathology driving it.

http://www.futurity.org/gait-hippocampus-brains-dementia-1472892/

Reference: 

Source: 

Topics: 

tags development: 

tags lifestyle: 

tags problems: 

Vascular health linked to dementia risk

  • A large study found a better cardiovascular health score was linked to a lower dementia risk and slower rates of cognitive decline, with both aspects reducing with each positive factor.
  • A large, long-running study found that higher systolic blood pressure at age 50 was linked to a greater risk of developing dementia, even when below the threshold for hypertension.
  • A large study reports that aggressive lowering of systolic blood pressure reduced the risk of MCI and dementia.
  • A long-running study found that older adults with high levels of arterial stiffness were more likely to develop dementia during the next 15 years.
  • Hypertensive rats exhibited larger ventricles, decreased brain volume, and impaired fluid transport in the brain possibly linked to impaired clearance of amyloid proteins.

Optimal levels of cardiovascular health in older age associated with lower dementia risk

A French study involving 6,626 older adults (65+) found that having optimal levels in more measures of cardiovascular health (nonsmoking, weight, diet, physical activity, cholesterol, blood glucose and blood pressure) was associated with lower dementia risk and slower rates of cognitive decline. Dementia risk and rates of cognitive decline lowered with each additional metric at the recommended optimal level.

The measures come from an American Heart Association seven-item checklist aimed at preventing cardiovascular disease.

https://www.eurekalert.org/pub_releases/2018-08/jn-hol081618.php

Dementia risk increased in 50-year-olds with blood pressure below hypertension threshold

New findings from the large, long-running Whitehall II study revealed that 50-year-olds who had blood pressure that was higher than normal but still below the usual threshold for treating hypertension, were at increased risk of developing dementia in later life.

This increased risk was seen even when they didn’t have other heart or blood vessel-related problems.

The study involved 8,639 people, of whom 32.5% were women. Participants were aged between 35-55 in 1985, and had their blood pressure measured in 1985, 1991, 1997 and 2003. 385 (4.5%) developed dementia by 2017.

Those who had a systolic blood pressure of 130 mmHg or more at the age of 50 had a 45% greater risk of developing dementia than those with a lower systolic blood pressure at the same age. This association was not seen at the ages of 60 and 70, and diastolic blood pressure was not linked to dementia.

https://www.eurekalert.org/pub_releases/2018-06/esoc-dri061118.php

https://www.theguardian.com/science/2018/jun/13/dementia-risk-to-50-year-olds-with-raised-blood-pressure-study

Intensive blood pressure control reduces risk of MCI

Preliminary results from the Systolic Blood Pressure Intervention Trial (SPRINT) has found that aggressive lowering of systolic blood pressure produced significant reductions in the risk of MCI, and MCI/dementia.

The randomized clinical trial compared an intensive strategy with a systolic blood pressure goal of less than 120 mm Hg and a standard care strategy targeting a systolic blood pressure goal of less than 140 mm Hg. The study involved 9,361 hypertensive older adults (mean age 67.9).

The intensive treatment group had a 19% lower rate of new cases of MCI, and the combined outcome of MCI plus probable all-cause dementia was 15% lower. Serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure occurred more frequently in the intensive-treatment group (4.7% vs 2.5%).

Participants were seen monthly for the first 3 months and every 3 months thereafter. Medications were adjusted on a monthly basis and lifestyle modification was encouraged. 30% of the participants were African American and 10% were Hispanic.

Preliminary results from 673 participants in the trial revealed that total white matter lesion (WML) volume increased in both treatment groups, but the increase was significantly less in the intensive treatment group. There was no significant difference in total brain volume change.

The findings were reported at the Alzheimer's Association International Conference (AAIC) 2018 in Chicago.

https://www.eurekalert.org/pub_releases/2018-07/aa-sib072218.php

Arterial stiffness linked to dementia risk

A long-running study involving 356 older adults (average age 78) found that those with high levels of arterial stiffness were 60% more likely to develop dementia during the next 15 years compared to those with lower levels.

Arterial stiffness is correlated with subclinical brain disease and cardiovascular risk factors, but adjusting for these factors didn't reduce the association between arterial stiffness and dementia — indicating that arterial stiffness and subclinical brain damage markers are independently related to dementia risk.

Arterial stiffening can be reduced by antihypertensive medication and perhaps also healthy lifestyle changes such as exercise. This study found that exercise at an average age of 73 was associated with lower arterial stiffness five years later.

https://www.eurekalert.org/pub_releases/2018-10/uops-lsi101518.php

Hypertension linked to brain atrophy & poorer waste management

A rat study found that hypertensive rats exhibited larger ventricles, decreased brain volume, and impaired fluid transport. It’s suggested that hypertension interferes with the clearance of macromolecules from the brain, such as amyloid-beta.

https://www.eurekalert.org/pub_releases/2019-06/sfn-hb061119.php

Reference: 

Samieri C, Perier M, Gaye B, et al. Association of Cardiovascular Health Level in Older Age With Cognitive Decline and Incident Dementia. JAMA. 2018;320(7):657–664. doi:10.1001/jama.2018.11499

Abell, J. et al. 2018. Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration and threshold used to define hypertension. European Heart Journal. doi:10.1093/eurheartj/ehy288

[4495] Cui, C., Sekikawa A., Kuller L. H., Lopez O. L., Newman A. B., Kuipers A. L., et al.
(2018).  Aortic Stiffness is Associated with Increased Risk of Incident Dementia in Older Adults.
Journal of Alzheimer's Disease. 66(1), 297 - 306.

[4496] Mortensen, K. Nygaard, Sanggaard S., Mestre H., Lee H., Kostrikov S., Xavier A. L. R., et al.
(2019).  Impaired Glymphatic Transport in Spontaneously Hypertensive Rats.
Journal of Neuroscience. 39(32), 6365 - 6377.

Topics: 

tags problems: 

Stress in midlife affects cognitive decline later in life

  • A large long-running study found that stressful life experiences (but not traumatic events) during middle-age were associated with greater memory decline in later life — but only for women.
  • A large long-running study found that middle-aged adults with higher levels of the stress hormone cortisol had poorer cognition than those with average cortisol levels, and this was also associated with greater brain atrophy.
  • A study found that older adults (65-95) who responded to stressful events with more negative emotions showed greater fluctuations in cognitive performance.

Stressors in middle age linked to cognitive decline in older women

Data from some 900 older adults has linked stressful life experiences among middle-aged women, but not men, to greater memory decline in later life.

Previous research has found that the effect of age on the stress response is three times greater in women than in men.

Having a greater number of stressful life experiences over the last year in midlife in women was linked to a greater decline in recalling words later and recognizing those words. There was no association, however, to traumatic events — suggesting that ongoing stress has more of a negative effect on cognition.

The data came from 909 Baltimore residents participating in the National Institute of Mental Health Epidemiologic Catchment Area study, begun in 1981. Participants were an average age of 47 during their mid-life check-in in the 90s.

https://www.eurekalert.org/pub_releases/2019-08/jhm-im080219.php

https://www.futurity.org/mid-life-stress-women-memory-alzheimers-2127072-2/

Stress hormone linked to impaired memory, smaller brain in middle age

Data from 2,231 participants (mean age 48.5) in the Framingham Heart Study has found that adults in their 40s and 50s with higher levels of the stress hormone cortisol had poorer cognition than those with average cortisol levels. Higher cortisol was also associated with smaller brain volumes.

There was no association between higher cortisol level and APOE genotype.

Age, sex, smoking and body mass index were taken into account in the analysis.

https://www.eurekalert.org/pub_releases/2018-10/uoth-sci102418.php

Response to daily stressors could affect brain health in older adults

A study following 111 older adults (65-95) for 2½ years, has found that those who responded to stressful events with more negative emotions and reported a more dour mood in general showed greater fluctuations in their performance on cognitive tests.

Cognitive testing occurred every six months, for six days over a two-week period.

Stressful events and emotional reactions were assessed by self-report.

Interestingly, there were age differences. For the oldest participants (late 70s and older), being more reactive to stressors than usual contributed to worse cognitive performance, but those in their late 60s to mid-70s actually did better on the test if they reported more stressors.

https://www.eurekalert.org/pub_releases/2018-11/osu-rtd111918.php

Reference: 

Munro, C. A., Wennberg, A. M., Bienko, N., Eaton, W. W., Lyketsos, C. G., & Spira, A. P. (2019). Stressful life events and cognitive decline: Sex differences in the Baltimore Epidemiologic Catchment Area Follow-Up Study. International Journal of Geriatric Psychiatry, 34(7), 1008–1017. https://doi.org/10.1002/gps.5102

[4483] Echouffo-Tcheugui, J. B., Conner S. C., Himali J. J., Maillard P., DeCarli C. S., Beiser A. S., et al.
(2018).  Circulating cortisol and cognitive and structural brain measures.
Neurology. 91(21), e1961.

[4482] Stawski, R., Cerino E., Witzel D., & MacDonald S\.
(Submitted).  Daily Stress Processes as Contributors to and Targets for Promoting Cognitive Health in Later Life.
Psychosomatic Medicine. 81(1), 81 - 89.

Source: 

Topics: 

tags development: 

tags memworks: 

tags problems: 

Alzheimer's produces early brain atrophy

  • A large study finds those who go on to develop Alzheimer's show atrophy of the hippocampus before age 40, and in the amygdala around age 40.

Brain scans from over 4,000 people, across the age range (9 months to 94 years) and including 1,385 Alzheimer's patients, has revealed an early divergence between those who go on to develop Alzheimer’s and those who age normally. This divergence is seen in early atrophy of the hippocampus before age 40, and in the amygdala around age 40.

https://www.eurekalert.org/pub_releases/2019-03/c-ahd030819.php

https://www.nature.com/articles/s41598-019-39809-8

Reference: 

Source: 

Topics: 

tags problems: 

Cognitive tests for MCI & Alzheimer's

  • A study involving nearly 600 older adults found that using two different episodic memory tests markedly improved MCI diagnosis, compared with only using one.
  • A large study found that the clock drawing test was better than the MMSE in identifying cognitive impairment, and concludes it should be given to all patients with high blood pressure.
  • A largish study of middle-aged men confirmed that practice effects mask cognitive decline in those who have experience repeated testing.
  • A large study indicates that verb fluency is a better test than the more usual word fluency tests, and poorer verb fluency was linked to faster decline to MCI and progression from MCI to dementia.
  • A smallish study found that a brief, simple number naming test differentiates between cognitively healthy older adults and those with MCI or Alzheimer's 90% of the time.
  • A study involving 450 patients with memory problems found that those with anosognosia (unawareness of such problems) had higher rates of amyloid-beta clumps and were more likely to develop dementia in the next 2 years.
  • Another larger study found that those with anosognosia  had reduced glucose uptake in specific brain regions.
  • A new cognitive test that assesses relational memory has been found to be effective in distinguishing very early mild Alzheimer's from normal aging.

Memory tests predict brain atrophy and Alzheimer's disease

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.

https://www.eurekalert.org/pub_releases/2018-12/uoh-mtp121018.php

Clock drawing test should be done routinely in patients with high blood pressure

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.

https://www.eurekalert.org/pub_releases/2018-08/esoc-cdc082318.php

Repeated cognitive testing can mask early signs of dementia

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.

https://www.eurekalert.org/pub_releases/2018-07/uoc--pir071118.php

Verb fluency helpful in detecting early cognitive impairment and predicting dementia

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.

https://www.eurekalert.org/pub_releases/2018-03/ip-tro031618.php

Effectiveness of brief, simple test to screen for MCI

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.

http://www.eurekalert.org/pub_releases/2016-07/bumc-sse070516.php

Not being aware of memory problems predicts onset of Alzheimer's

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.

https://www.eurekalert.org/pub_releases/2018-02/mu-nba021518.php

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.

https://www.eurekalert.org/pub_releases/2017-10/cfaa-buo101017.php

Cognitive test differentiates between Alzheimer's and normal aging

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.

http://www.eurekalert.org/pub_releases/2014-05/uoia-ctc052014.php

Reference: 

[4439] 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.

[4440] 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.

[4442] 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.

[4443] 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.

[4444] 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

Source: 

Topics: 

tags problems: 

Genes linked to Alzheimer's

  • Very large study finds 5 new genes linked to increased Alzheimer's risk.
  • A rare gene variant that protects APOE4 gene carriers from getting Alzheimer's has been identified.
  • Two large surveys found that verbal recall score was significantly affected by TOMM40 genotype. TOMM40 is adjacent to APOE on their chromosome.
  • A study found that TOMM40's effect on Alzheimer's depends on parental history.
  • Data from three very large studies has produced a tool for assessing an individual's genetic risk for developing Alzheimer's, based on 31 genetic markers.
  • A small study found that, of the top 9 genes that affect Alzheimer's risk, excluding the APOE gene, only 2 affect brain atrophy.
  • A new gene variant that is associated with greater amyloid plaque than APOE4 has been identified.

Five new risk genes for Alzheimer's disease

Genetic data from more than 94,000 individuals has revealed five new risk genes for Alzheimer's disease, and confirmed 20 known others. The new genes are: IQCK, ACE, ADAM10, ADAMTS1 and WWOX.

The findings support developing evidence that groups of genes associated with specific biological processes, such as cell trafficking, lipid transport, inflammation and the immune response, are "genetic hubs" that are an important part of the disease process.

The study also suggests that variants affecting APP and amyloid beta protein processing are associated with both early-onset autosomal dominant Alzheimer's and with late onset Alzheimer's. In addition, for the first time, the study implicated a genetic link to tau binding proteins.

The findings follow on from a 2013 report.

https://www.eurekalert.org/pub_releases/2019-02/nioa-dsu022719.php

Gene variant found that protects against Alzheimer's

A large study involving families that had a large number of resilient individuals (those who carried the APOE4 gene but remained healthy into advanced age) has found that the resilient subjects shared a variant in the RAB10 gene while those who got the disease did not share that genetic variant.

https://www.eurekalert.org/pub_releases/2017-11/byu-rig112917.php

Gene linked to Alzheimer's gene affects age-related cognitive decline

TOMM40 and APOE genes are adjacent to each other on chromosome 19, and have sometimes been used as proxies for one another in genetic studies. TOMM40 has largely been thought of as a “sidekick” to ApoE4. But new research suggests it may have a stronger role.

Data from two large surveys — the U.S. Health and Retirement Study and the English Longitudinal Study of Ageing — found that verbal recall score was significantly affected by TOMM40 genotype.

The researchers examined 1.2 million gene variations across the human genome. TOMM40 was the only one with a strong link to declines in immediate recall and level of delayed recall. APOE4 also was linked but not as strongly.

To test immediate recall, an interviewer read a list of 10 nouns and then asked the participant to repeat the words back immediately. For delayed recall, the interviewer waited five minutes and then asked the participant to recall the list. Test scores ranged from 0 to 10. The average score for immediate recall was 5.7 words out of 10, and the delayed recall scoring average was 4.5 words out of 10. A large gap between the two sets of scores can signal the development of Alzheimer's or some other form of dementia.

Those who had received a likely diagnosis of dementia or a dementia-like condition were excluded from the study.

https://www.eurekalert.org/pub_releases/2017-09/uosc-it091417.php

Family history of Alzheimer's may alter gene that increases risk

There have been conflicting findings about whether the gene, TOMM40 (Translocase of Outer Mitochondrial Membrane-40kD) increases the risk for Alzheimer's. A new study, however, has found that its impact on memory and dementia risk depends on two other factors: parental history of Alzheimer's, and the length of a specific section of the gene.

In the study, late middle-aged people with a family history (parent with Alzheimer’s) and longer version of the gene had twice as much memory loss up to 10 years later as someone with a family history and a short version of the gene. A similar but stronger finding was seen in a group of older adults.

https://www.eurekalert.org/pub_releases/2017-05/isu-fho051917.php

Multiple genetic markers combine to estimate Alzheimer's risk

Genotype data from three very large studies has enabled researchers to construct a test that can be used to calculate any individual’s yearly risk for onset of Alzheimer's. The polygenic hazard score (PHS) is based on 31 genetic markers.

Those with the highest PHS (top 10%) were more than three times more likely to develop Alzheimer's than those with the lowest PHS, and to do so more than 10 years earlier.

In people with the high-risk version of ApoE, those ranked in the top 10% of risk on the new test got Alzheimer’s at an average age of 84 years, compared with 95 years for those ranked in the lowest 10%.

The study also demonstrates that, aside from ApoE, there are thousands of background genetic variations that each have a tiny influence on Alzheimer’s risk, but whose cumulative influence is substantial.

But note that this doesn’t tell us that it’s all about genes! Lifestyle factors are still very important in determining whether you actually get Alzheimer's.

https://www.eurekalert.org/pub_releases/2017-03/p-mgm031317.php

https://www.theguardian.com/society/2017/mar/22/new-alzheimers-test-can-predict-age-when-disease-will-appear

Two Alzheimer's risk genes linked to brain atrophy

A study involving 50 older adults (50+) with no cognitive difficulties and 90 who had been diagnosed with MCI has examined the top nine genetic variants associated with Alzheimer's risk, excluding the APOe4 gene, to find which of them was associated with atrophy in the cortex and hippocampus.

Only ABCA7 and MA4A6A were associated with brain atrophy.

http://www.eurekalert.org/pub_releases/2015-12/iu-tar122315.php

New gene linked to amyloid beta plaque buildup

A study involving nearly 500 individuals has found that a variant of the IL1RAP gene was associated with higher rates of amyloid plaque buildup in the brains of Alzheimer's patients and older adults at risk for the disease, and its effect on amyloid buildup was stronger than that of APOE4.

IL1RAP codes for the key immune signaling factor Interleukin-1 Receptor Accessory Protein, which plays a central role in the activity of microglia, the immune system cells that clear up waste products such as plaques and tangles.

Additionally, the IL1RAP variant was associated with:

  • a lower level of microglial activity
  • greater atrophy of the temporal cortex
  • faster cognitive decline
  • greater likelihood of progression from MCI to Alzheimer's.

http://www.eurekalert.org/pub_releases/2015-10/iu-rin100515.php

Reference: 

[4419] Kunkle, B. W., & et al
(Submitted).  Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing | Nature Genetics.

[3586] Lambert, J-C., Ibrahim-Verbaas C. A., Harold D., Naj A. C., Sims R., Bellenguez C., et al.
(2013).  Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
Nature Genetics. 45(12), 1452 - 1458.

[4420] Ridge, P. G., Karch C. M., Hsu S., Arano I., Teerlink C. C., Ebbert M. T. W., et al.
(2017).  Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer’s disease resilience.
Genome Medicine. 9(1), 100.

[4422] Arpawong, T. E., Pendleton N., Mekli K., McArdle J. J., Gatz M., Armoskus C., et al.
(2017).  Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort.
PLOS ONE. 12(8), e0182448.

[4423] Willette, A. A., Webb J. L., Lutz M. W., Bendlin B. B., Wennberg A. M. V., Oh J. M., et al.
(2017).  AD FAMILY HISTORY MODULATES EFFECTS OF TOMM40 ‘523’ POLY-T ON MTL ATROPHY AND HYPOMETABOLISM IN PRECLINICAL AND AD COHORTS.
Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 13(7), P54 - P55.

[4424] Desikan, R. S., Fan C. Chieh, Wang Y., Schork A. J., Cabral H. J., L. Cupples A., et al.
(2017).  Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score.
PLOS Medicine. 14(3), e1002258.

[4412] Ramirez, L. M., Goukasian N., Porat S., Hwang K. S., Eastman J. A., Hurtz S., et al.
(2016).  Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy.
Neurobiology of Aging. 39, 82 - 89.

[4425] Ramanan, V. K., Risacher S. L., Nho K., Kim S., Shen L., McDonald B. C., et al.
(2015).  GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer’s disease implicates microglial activation gene IL1RAP.
Brain. 138(10), 3076 - 3088.

Topics: 

tags problems: 

Smoking, hypertension, diabetes & obesity each linked to poor brain health

  • A large study has found that smoking, high blood pressure, diabetes, and obesity are each linked to more brain atrophy, and damage to white matter.
  • The more of these you have, the greater the shrinkage and damage.

Brain scans of 9,772 people aged 44 to 79, who were enrolled in the UK Biobank study, have revealed that smoking, high blood pressure, high pulse pressure, diabetes, and high BMI — but not high cholesterol — were all linked to greater brain shrinkage, less grey matter and less healthy white matter.

Smoking, high blood pressure, and diabetes were the most important factors, but there was also a compound effect, with the number of vascular risk factors being associated with greater damage to the brain. On average, those with the highest vascular risk had nearly 3% less volume of grey matter, and one-and-a-half times the damage to their white matter, compared to people who had the lowest risk.

The brain regions affected were mainly those involved in ‘higher-order’ thinking, and those known to be affected early in the development of dementia.

The associations were as strong for middle-aged adults as for older ones, suggesting the importance of tackling these factors early.

While the effect size was small, the findings emphasize how vulnerable the brain is to vascular factors even in relatively healthy adults. This also suggests the potential of lifestyle changes for fighting cognitive decline.

Although this study didn't itself examine cognitive performance in its participants, other studies have shown links between cognitive impairment and vascular risk factors, particularly diabetes, obesity, hypertension, and smoking.

https://www.eurekalert.org/pub_releases/2019-03/esoc-shb030719.php

Cognitive decline in type 2 diabetes linked to white matter hyperintensities

While type 2 diabetes has been associated with cognitive problems, the mechanism has been unclear. Now a study involving 93 people with type 2 diabetes has found that greater white matter hyperintensities (indicative of cerebral small vessel disease) were associated with decreased processing speed (but not with memory or executive function).

https://www.eurekalert.org/pub_releases/2018-09/w-rem091818.php

Reference: 

Cox, Simon R. et al. 2019. Associations between vascular risk factors and brain MRI indices in UK Biobank. European Heart Journal. doi:10.1093/eurheartj/ehz100

[4395] Mankovsky, B., Zherdova N., van den Berg E., Biessels G.-J., & de Bresser J.
(2018).  Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus.
Diabetic Medicine. 35(12), 1663 - 1670.

 

Topics: 

tags development: 

tags lifestyle: 

tags problems: 

Smell tests provide early evidence of dementia

  • It seems clear now that a substantial decline in sense of smell is a very early sign of developing MCI and Alzheimer's.
  • Several tests have been developed to assess this.
  • It should always be remembered that there is substantial difference between individuals in their 'natural' sense of smell, and this needs to be taken into account in any test.

In the past few months, several studies have come out showing the value of three different tests of people's sense of smell for improving the accuracy of MCI and Alzheimer's diagnosis, or pointing to increased risk. The studies also add to growing evidence that a decline in sense of smell is an early marker for mild cognitive impairment and Alzheimer’s. Indeed, it appears that this sensory loss is a very early symptom, preceding even the shrinking of the entorhinal cortex (the first brain region to show signs of atrophy).

Smell test improves accuracy of MCI & Alzheimer's diagnosis

A simple, commercially available test known as the Sniffin' Sticks Odor Identification Test, in which subjects must try to identify 16 different odors, was given to 728 older adults, as well as a standard cognitive test (the Montreal Cognitive Assessment).

The participants had already been evaluated by doctors and classified as being healthy (292 subjects), having MCI (174: 150 aMCI, 24 naMCI), or having Alzheimer's (262).

It was found that, while the cognitive test alone correctly classified 75% of people with MCI, the number rose to 87% when the sniff test results were added. Diagnosis of Alzheimer's, and of subtypes within MCI, was also improved.

The smell test normally takes 5 to 8 minutes to administer; the researchers are trying to get it down to 3 minutes, to encourage greater use.

A new smell test

Another recent study validates a new smell test which is rather more complicated. The test was developed because the standard University of Pennsylvania Smell Identification Test doesn’t take into account the great variation in olfactory ability among healthy individuals. The ability of normal individuals to recognize and discriminate between odors can vary by as much as 40 times!

The new test is actually four tests:

  • In the OPID (Odor Percept IDentification)-10 test, participants are presented with 10 odors (menthol, clove, leather, strawberry, lilac, pineapple, smoke, soap, grape, lemon) for two seconds each. They are then asked whether the scent is familiar and given a choice of four of the 10 words from which are asked to pick the best one that describes the odor.
  • The Odor Awareness Scale (OAS) assesses their overall attention to environmental odors and how they are affected emotionally and behaviorally by scents.
  • The OPID-20 test includes an additional 10 odors (banana, garlic, cherry, baby powder, grass, fruit punch, peach, chocolate, dirt, orange). Participants are first asked whether a presented odor was included in the OPID-10 test and then asked which word best describes the odor. Their ability to remember odors from the first test determines their POEM (Percepts of Odor Episodic Memory) score.
  • In the Odor Discrimination (OD) test, participants are presented with two consecutive odors and asked whether they were different or the same, a process that is repeated 12 times with different paired scents.

The study involved 183 older adults, of whom 70 were cognitively normal, 74 tested normal but were concerned about their cognitive abilities, 29 had MCI and 10 had been diagnosed with possible or probable Alzheimer's disease.

Results of the OPID-20 test significantly differentiated among the four groups of participants, and those results correlated with the thinning of the hippocampus and the entorhinal cortex. Participants' ability to remember a previously presented aroma, as reflected in the POEM score, was also significant, with participants with Alzheimer's disease performing at no better than chance.

POEM scores of the two cognitively normal groups were compared with what would have been predicted based on their ability to identify and differentiate between odors, as reflected in the OAS and OD tests. Poor POEM performers were more likely to have the ‘Alzheimer's gene’ (APOEe4), showed thinning of the entorhinal cortex, and poorer cognitive performance over time.

Validation of UPSIT

However, two 2016 studies support the use of the University of Pennsylvania Smell Identification Test (UPSIT), and suggest it may offer a practical, low-cost alternative to other tests.

In one study, UPSIT was administered to 397 older adults (average age 80) without dementia, who were also given an MRI scan to measure the thickness of the entorhinal cortex (the first brain region to be affected by Alzheimer's disease). After four years, 50 participants (12.6%) had developed dementia, and nearly 20% had signs of cognitive decline.

Low UPSIT scores, but not entorhinal cortical thickness, were significantly associated with dementia and Alzheimer's disease, and with cognitive impairment. Entorhinal cortical thickness was significantly associated with UPSIT score in those who transitioned from MCI to dementia.

In other words, it looks like impairment in odor identification precedes thinning in the entorhinal cortex.

In another study, UPSITwas administered to 84 older adults, of whom 58 had MCI, as well as either beta amyloid PET scanning or analysis of cerebrospinal fluid. After six months, 67% had signs of memory decline, and this was predicted by amyloid-beta levels (assessed by either method), but not UPSIT score. However, participants with a score of less than 35 were more than three times as likely to have memory decline as those with higher UPSIT scores.

The researchers suggest the association wasn’t as strong in this study because of the younger age of participants (median age 71), their higher education, and the short follow-up.

https://www.eurekalert.org/pub_releases/2016-12/uops-psc122016.php

https://www.eurekalert.org/pub_releases/2016-11/mgh-atr111416.php

http://www.eurekalert.org/pub_releases/2016-07/cumc-stm072516.php

Reference: 

[4209] Quarmley, M., Moberg P. J., Mechanic-Hamilton D., Kabadi S., Arnold S. E., Wolk D. A., et al.
(2017).  Odor Identification Screening Improves Diagnostic Classification in Incipient Alzheimer’s Disease.
Journal of Alzheimer's Disease. 55(4), 1497 - 1507.

[4210] Dhilla, A. Alefiya, Asafu-Adjei J., Delaney M. K., Kelly K. E., Gomez-Isla T., Blacker D., et al.
(2016).  Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly.
Annals of Neurology. 80(6), 846 - 857.

Lee, Seonjoo et al. 2016. Predictive Utility of Entorhinal Cortex Thinning and Odor Identification Test for Transition to Dementia and Cognitive Decline in an Urban Community Population. Presented at the Alzheimer's Association's International Conference in Toronto.

Kreisl, William et al. 2016. Both Odor Identification and Amyloid Status Predict Memory Decline in Older Adults. Presented at the Alzheimer's Association's International Conference in Toronto.

Topics: 

tags development: 

tags memworks: 

tags problems: 

Different kinds of physical activity improve brain volume & cut Alzheimer's risk

  • A large long-running study adds to growing evidence that higher levels of physical activity reduce brain atrophy and Alzheimer's risk, and shows that many types of aerobic activity are beneficial.

Data from 876 patients (average age 78) in the 30-year Cardiovascular Health Study show that virtually any type of aerobic physical activity can improve brain volume and reduce Alzheimer's risk.

A higher level of physical activity was associated with larger brain volumes in the frontal, temporal, and parietal lobes including the hippocampus, thalamus and basal ganglia. Among those with MCI or Alzheimer's (25% of the participants), higher levels of physical activity were also associated with less brain atrophy. An increase in physical activity was also associated with larger grey matter volumes in the left inferior orbitofrontal cortex and the left precuneus.

Further analysis of 326 of the participants found that those with the highest energy expenditure were half as likely to have developed Alzheimer's disease five years later.

Physical activity was assessed using the Minnesota Leisure-Time Activities questionnaire, which calculates kilocalories/week using frequency and duration of time spent in 15 different leisure-time activities: swimming, hiking, aerobics, jogging, tennis, racquetball, walking, gardening, mowing, raking, golfing, bicycling, dancing, calisthenics, and riding an exercise cycle.

The study does not look at whether some types of physical activity are better than others, unfortunately, but its message that overall physical activity, regardless of type, helps in the fight against cognitive impairment is encouraging.

http://www.eurekalert.org/pub_releases/2016-03/ip-dko030916.php

http://www.eurekalert.org/pub_releases/2016-03/uops-bmc031016.php

Reference: 

Topics: 

tags development: 

tags lifestyle: 

tags problems: 

Omega 3 levels affect whether B vitamins can slow brain's decline

  • B vitamins can help many older adults with mild cognitive impairment, but only if they have good levels of omega-3 fatty acids.

A study involving 266 people with mild cognitive impairment (aged 70+) has found that B vitamins are more effective in slowing cognitive decline when people have higher omega 3 levels.

Participants were randomly selected to receive either a B-vitamin supplement (folic acid, vitamins B6 and B12) or a placebo pill for two years. The vitamins had little to no effect for those with low levels of omega-3 fatty acids, but were very effective for those with high baseline omega-3 levels.

Levels of DHA appeared to be more important than levels of EPA, but more research is needed to confirm that.

The finding may help to explain why research looking at the effects of B vitamins, or the effects of omega-3 oils, have produced inconsistent findings.

The study followed research showing that B vitamins can slow or prevent brain atrophy and memory decline in people with MCI, and they were most effective in those who had above average blood levels of homocysteine.

http://www.eurekalert.org/pub_releases/2016-01/uoo-ola011916.php

Reference: 

Topics: 

tags development: 

tags lifestyle: 

tags problems: 

Pages

Subscribe to RSS - brain atrophy