brain atrophy

Benefits of exercise for the brain

  • A small study found moderate-intensity exercise was more beneficial for immediate memory performance than other levels of exercise or forms of rest.
  • A small study found low-intensity exercise triggers different brain networks than high-intensity exercise.
  • A large study found that better cardiorespiratory fitness was strongly associated with more gray matter.
  • Similarly, a review of clinical trials found that aerobic exercise protected against brain shrinkage (reducing gray matter).

Moderate intensity exercise can benefit memory performance

Three experiments involving a total of 59 people provides more evidence that moderate intensity exercise (e.g., brisk walking, water aerobics, cycling) is enough for cognitive improvement. Indeed, moderate intensity exercise had the most beneficial effect on memory performance.

The experiments compared exercise at three levels of intensity (low, moderate, high), high-intensity interval training (HIIT), active rest (cognitive engagement), and passive rest (no cognitive activity). Memory was tested using a recognition test with an 80–90 minute retention interval (people were shown items, then 80-90 minutes later, had to say whether an item was the same as one seen before, or new).

High & low exercise intensity found to influence brain function differently

A study involving 25 male athletes has found that low-intensity exercise triggers brain networks involved in cognition control and attention processing, while high-intensity exercise primarily activates networks involved in affective/emotion processing.

The athletes exercised on a treadmill, performing low- and high-intensity exercise bouts for 30 minutes on separate days.

Exercising good for your gray matter

A German study involving 2,013 adults (aged 21-84) found that better cardiorespiratory fitness was strongly associated with increased gray matter volume and total brain volume. Particular brain regions affected were the left middle temporal gyrus, righ hippocampal gyrus, left orbitofrontal cortex, and bilateral cingulate cortex.

Cardiorespiratory fitness was measured using peak oxygen uptake and other standards while participants used an exercise bike.

Cardiorespiratory exercise includes walking briskly, running, biking and just about any other exercise that gets your heart pumping.

Exercise protects against brain shrinkage

A review of 14 clinical trials which examined brain scans from 737 people before and after aerobic exercise programs or in control conditions concluded that aerobic exercise significantly increased the size of the left region of the hippocampus, though it had no effect on total hippocampal volume (implying that the right side shrank).

Importantly, the effect on brain volume was not due to an increase in brain matter, but protection against the shrinkage that occurs over time. In other words, as one researcher noted, exercise can be seen as a maintenance program for the brain.

Participants included healthy adults, people with mild cognitive impairment such as Alzheimer’s and people with a clinical diagnosis of mental illness including depression and schizophrenia. Ages ranged from 24 to 76 years with an average age of 66.

The researchers examined effects of aerobic exercise, including stationary cycling, walking, and treadmill running. The length of the interventions ranged from three to 24 months with a range of 2-5 sessions per week.

Reference: 

Pyke, W., Ifram, F., Coventry, L., Sung, Y., Champion, I., & Javadi, A.-H. (2020). The effects of different protocols of physical exercise and rest on long-term memory. Neurobiology of Learning and Memory, 167, 107128. https://doi.org/10.1016/j.nlm.2019.107128

Schmitt, A., Upadhyay, N., Martin, J. A., Rojas, S., Strüder, H. K., & Boecker, H. (2019). Modulation of Distinct Intrinsic Resting State Brain Networks by Acute Exercise Bouts of Differing Intensity. Brain Plasticity, 5(1), 39–55. https://doi.org/10.3233/BPL-190081

Wittfeld, K., Jochem, C., Dörr, M., Schminke, U., Gläser, S., Bahls, M., Markus, M. R. P., Felix, S. B., Leitzmann, M. F., Ewert, R., Bülow, R., Völzke, H., Janowitz, D., Baumeister, S. E., & Grabe, H. J. (2020). Cardiorespiratory Fitness and Gray Matter Volume in the Temporal, Frontal, and Cerebellar Regions in the General Population. Mayo Clinic Proceedings, 95(1), 44–56. https://doi.org/10.1016/j.mayocp.2019.05.030

Firth, J., Stubbs, B., Vancampfort, D., Schuch, F., Lagopoulos, J., Rosenbaum, S., & Ward, P. B. (2018). Effect of aerobic exercise on hippocampal volume in humans: A systematic review and meta-analysis. NeuroImage, 166, 230–238. https://doi.org/10.1016/j.neuroimage.2017.11.007

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Improving fitness may counteract brain atrophy in older adults, including those with MCI

  • A small study involving physically inactive older adults found that a three-month exercise program reversed some brain atrophy.

A study involving 30 previously physically inactive older adults (aged 61-88) found that a three-month exercise program reversed some brain atrophy.

Participants included 14 with MCI. The exercise program included moderate intensity walking on a treadmill four times a week over a twelve-week period. On average, cardiorespiratory fitness improved by about 8% as a result of the training in both the healthy and MCI participants. Fitness was assessed using peak oxygen capacity rates.

Those who showed the greatest improvements in fitness had the most growth in cortical thickness. Those with MCI showed greater improvements compared to healthy group in the left insula and superior temporal gyrus, two brain regions that have been shown to exhibit accelerated neurodegeneration in Alzheimer’s disease.

Reference: 

Reiter, K., Nielson, K. A., Smith, T. J., Weiss, L. R., Alfini, A. J., & Smith, J. C. (2015). Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment. Journal of the International Neuropsychological Society, 21(Special Issue 10), 757–767. https://doi.org/10.1017/S135561771500079X

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Is soda bad for your brain, especially diet soda?

Data from the large and very long-running Framingham Heart Study has revealed that people who drink sugary drinks frequently are more likely to have poorer memory, smaller overall brain volume, and a significantly smaller hippocampus. Moreover, a second study found that those who drank diet soda daily were almost three times as likely to develop stroke and dementia over a 10-year period, compared to those who didn’t – suggesting that substituting artificial sweeteners for the sugar doesn’t make matters better.

Age, smoking, diet quality, and other factors were taken into account, but the analysis couldn’t completely control for preexisting conditions like diabetes. Diabetics tend to drink more diet soda on average, as a way to limit their sugar consumption, and some of the correlation between diet soda intake and dementia may be due to diabetes, a known risk factor for dementia.

Reference: 

Pase, M. P., Himali, J. J., Jacques, P. F., DeCarli, C., Satizabal, C. L., Aparicio, H., Vasan, R. S., Beiser, A. S., & Seshadri, S. (2017). Sugary beverage intake and preclinical Alzheimer’s disease in the community. Alzheimer’s & Dementia, 13(9), 955–964. https://doi.org/10.1016/j.jalz.2017.01.024

Pase Matthew P., Himali Jayandra J., Beiser Alexa S., Aparicio Hugo J., Satizabal Claudia L., Vasan Ramachandran S., Seshadri Sudha, & Jacques Paul F. (2017). Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia. Stroke, 48(5), 1139–1146. https://doi.org/10.1161/STROKEAHA.116.016027

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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/

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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.

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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.

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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

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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

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