MCI

mild cognitive impairment

Metabolic syndrome linked to memory loss in older people

March, 2011

Three more studies point to the increased risk of memory loss in older adults with cardiovascular problems.

The new label of ‘metabolic syndrome’ applies to those having three or more of the following risk factors: high blood pressure, excess belly fat, higher than normal triglycerides, high blood sugar and low high-density lipoprotein (HDL) cholesterol (the "good" cholesterol). Metabolic syndrome has been linked to increased risk of heart attack.

A new French study, involving over 7,000 older adults (65+) has found that those with metabolic syndrome were 20% more likely to show cognitive decline on a memory test (MMSE) over a two or four year interval. They were also 13% more likely to show cognitive decline on a visual working memory test. Specifically, higher triglycerides and low HDL cholesterol were linked to poorer memory scores; diabetes (but not higher fasting blood sugar) was linked to poorer visual working memory and word fluency scores.

The findings point to the importance of managing the symptoms of metabolic syndrome.

High cholesterol and blood pressure in middle age tied to early memory problems

Another study, involving some 4800 middle-aged adults (average age 55), has found that those with higher cardiovascular risk were more likely to have lower cognitive function and a faster rate of cognitive decline over a 10-year period. A 10% higher cardiovascular risk was associated not only with increased rate of overall mental decline, but also poorer cognitive test scores in all areas except reasoning for men and fluency for women.

The cardiovascular risk score is based on age, sex, HDL cholesterol, total cholesterol, systolic blood pressure and whether participants smoked or had diabetes.

Memory problems may be sign of stroke risk

A very large study (part of the REGARDS study) tested people age 45 and older (average age 67) who had never had a stroke. Some 14,842 people took a verbal fluency test, and 17,851 people took a word recall memory test. In the next 4.5 years, 123 participants who had taken the verbal fluency test and 129 participants who had taken the memory test experienced a stroke.

Those who had scored in the bottom 20% for verbal fluency were 3.6 times more likely to develop a stroke than those who scored in the top 20%. For the memory test, those who scored in the bottom 20% were 3.5 times more likely to have a stroke than those in the top quintile.

The effect was greatest at the younger ages. At age 50, those who scored in the bottom quintile of the memory test were 9.4 times more likely to later have a stroke than those in the top quintile.

 

Together, these studies, which are consistent with many previous studies, confirm that cardiovascular problems and diabetes add to the risk of greater cognitive decline (and possible dementia) in old age. And point to the importance of treating these problems as soon as they appear.

Reference: 

[2147] Raffaitin, C., Féart C., Le Goff M., Amieva H., Helmer C., Akbaraly T. N., et al.
(2011).  Metabolic syndrome and cognitive decline in French elders.
Neurology. 76(6), 518 - 525.

The findings of the second and third studies are to be presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011

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Predicting memory loss in healthy older adults

February, 2011

Having the ‘Alzheimer’s gene’ and showing reduced brain activity during a mental task combined to correctly predict future cognitive decline in 80% of healthy elders.

In a study in which 78 healthy elders were given 5 different tests and then tested for cognitive performance 18 months later, two tests combined to correctly predict nearly 80% of those who developed significant cognitive decline. These tests were a blood test to identify presence of the ‘Alzheimer’s gene’ (APOE4), and a 5-minute fMRI imaging scan showing brain activity during mental tasks.

The gene test in itself correctly classified 61.5% of participants (aged 65-88; mean age 73), showing what a strong risk factor this is, but when taken with activity on the fMRI test, the two together correctly classified 78.9% of participants. Age, years of education, gender and family history of dementia were not accurate predictors of future cognitive decline. A smaller hippocampus was also associated with a greater risk of cognitive decline.

These two tests are readily available and not time-consuming, and may be useful in identifying those at risk of MCI and dementia.

Reference: 

Woodard, J.L.  et al. 2010. Prediction of Cognitive Decline in Healthy Older Adults using fMRI. Journal of Alzheimer’s Disease, 21 (3), 871-885.

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Bilingualism delays onset of Alzheimer's symptoms

January, 2011

A second study confirms the dramatic effect of being bilingual, with bilingual speakers being diagnosed with Alzheimer’s more than 4 years later than monoglots.

Clinical records of 211 patients diagnosed with probable Alzheimer's disease have revealed that those who have spoken two or more languages consistently over many years experienced a delay in the onset of their symptoms by as much as five years. It’s thought that lifelong bilingualism may contribute to cognitive reserve in the brain, enabling it to compensate for memory loss, confusion, and difficulties with problem-solving and planning.

Of the 211 patients of the Sam and Ida Ross Memory Clinic at Baycrest, 102 patients were classified as bilingual and 109 as monolingual. Bilingual patients had been diagnosed with Alzheimer's 4.3 years later than the monolingual patients on average, and had reported the onset of symptoms 5.1 years later. The groups were equivalent on measures of cognitive and occupational level, there was no apparent effect of immigration status, and there were no gender differences.

The findings confirm an earlier study from the same researchers, from the clinical records of 184 patients diagnosed with probable Alzheimer's and other forms of dementia.

Reference: 

[2039] Craik, F. I. M., Bialystok E., & Freedman M.
(2010).  Delaying the onset of Alzheimer disease.
Neurology. 75(19), 1726 - 1729.

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Importance of exercise for Alzheimer's gene carriers

January, 2011

A small study suggests that physical activity may be of greater benefit to those carrying the Alzheimer’s gene in protecting against cognitive decline.

A study involving 68 healthy older adults (65-85) has compared brain activity among four groups, determined whether or not they carry the Alzheimer’s gene ApoE4 and whether their physical activity is reported to be high or low. The participants performed a task involving the discrimination of famous people, which engages 15 different functional regions of the brain. Among those carrying the gene, those with higher physical activity showed greater activation in many regions than those who were sedentary. Moreover, physically active people with the gene had greater brain activity than physically active people without the gene.

And adding to the evidence supporting the potential for exercise to lower the risk of dementia, another recent study has found that after ten years exercise (in terms of the number of different types of exercises performed and number of exercise sessions lasting at least 20 minutes) was inversely associated with the onset of cognitive impairment. The study used data from the National Long Term Care Survey.

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Protein in the urine: A warning sign for cognitive decline

December, 2010

Two recent studies indicate that the presence of protein in the urine, even in small amounts, could be a warning sign that a patient may develop cognitive impairment with age.

A six-year study involving over 1200 older women (70+) has found that low amounts of albumin in the urine, at levels not traditionally considered clinically significant, strongly predict faster cognitive decline in older women. Participants with a urinary albumin-to-creatinine ratio of >5 mcg/mg at the start of the study experienced cognitive decline at a rate 2 to 7 times faster in all cognitive measures than that attributed to aging alone over an average 6 years of follow-up. The ability most affected was verbal fluency. Albuminuria may be an early marker of diffuse vascular disease.

Data from 19,399 individuals participating in the Renal Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, of whom 1,184 (6.1%) developed cognitive impairment over an average follow-up of 3.8 years, has found that those with albuminuria were 1.31-1.57 times more likely to develop cognitive impairment compared to individuals without albuminuria. This association was strongest for individuals with normal kidney function. Conversely, low kidney function was associated with a higher risk for developing cognitive impairment only among individuals without albuminuria. Surprisingly, individuals with albuminuria and normal kidney function had a higher probability for developing cognitive impairment as compared to individuals with moderate reductions in kidney function in the absence of albuminuria.

Both albuminuria and low kidney function are characteristics of kidney disease.

Reference: 

Lin, J., Grodstein, F., Kang, J.H. & Curhan, G. 2010. A Prospective Study of Albuminuria and Cognitive Decline in Women. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.

Tamura, M.K. et al. 2010. Albuminuria, Kidney Function and the Incidence of Cognitive Impairment in US Adults. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.

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Vascular disease underlies cognitive decline in healthy aging

December, 2010
  • New findings add to evidence that the key to not becoming cognitively impaired in old age is vascular health.

More evidence that vascular disease plays a crucial role in age-related cognitive impairment and Alzheimer’s comes from data from participants in the Alzheimer's Disease Neuroimaging Initiative.

The study involved more than 800 older adults (55-90), including around 200 cognitively normal individuals, around 400 people with mild cognitive impairment, and 200 people with Alzheimer's disease. The first two groups were followed for 3 years, and the Alzheimer’s patients for two. The study found that the extent of white matter hyperintensities (areas of damaged brain tissue typically caused by cardiovascular disease) was an important predictor of cognitive decline.

Participants whose white matter hyperintensities were significantly above average at the beginning of the study lost more points each year in cognitive testing than those whose white matter hyperintensities were average at baseline. Those with mild cognitive impairment or Alzheimer's disease at baseline had additional declines on their cognitive testing each year, meaning that the presence of white matter hyperintensities and MCI or Alzheimer's disease together added up to even faster and steeper cognitive decline.

The crucial point is that this was happening in the absence of major cardiovascular events such as heart attacks, indicating that it’s not enough to just reduce your cardiovascular risk factors to a moderate level — every little bit of vascular damage counts.

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New brief tool to screen for cognitive impairment in elderly patients

December, 2010

A 2-minute questionnaire does an excellent job of indicating older adults with cognitive impairment.

A simple new cognitive assessment tool with only 16 items appears potentially useful for identifying problems in thinking, learning and memory among older adults. The Sweet 16 scale is scored from zero to 16 (with 16 representing the best score) and includes questions that address orientation (identification of person, place, time and situation), registration, digit spans (tests of verbal memory) and recall. The test requires no props (not even pencil and paper) and is easy to administer with a minimum of training. It only takes an average of 2 minutes to complete.

A score of 14 or less correctly identified 80% of those with cognitive impairment (as identified by the Informant Questionnaire on Cognitive Decline in the Elderly) and correctly identified 70% of those who did not have cognitive impairment. In comparison, the standard MMSE correctly identified 64% of those with cognitive impairment and 86% of those who were not impaired. In other words, the Sweet 16 missed diagnosing 20% of those who were (according to this other questionnaire) impaired and incorrectly diagnosed as impaired 30% of those who were not impaired, while the MMSE missed 36% of those who were impaired but only incorrectly diagnosed as impaired 14% of those not impaired.

Thus, the Sweet 16 seems to be a great ‘first cut’, since its bias is towards over-diagnosing impairment. It should also be remembered that the IQCDE is not the gold standard for cognitive impairment; its role here is to provide a basis for comparison between the new test and the more complex MMSE. In comparison with a clinician’s diagnosis, Sweet 16 scores of 14 or less occurred in 99% of patients diagnosed by a clinician to have cognitive impairment and 28% of those without such a diagnosis.

The great benefit of the new test is of course its speed and simplicity, and it seems to offer great promise as an initial screening tool. Another benefit is that it supposedly is unaffected by the patient’s education, unlike the MMSE. The tool is open access.

The Sweet 16 was developed using information from 774 patients who completed the MMSE, and then validated using a different group of 709 older adults.

Reference: 

[1983] Fong, T. G., Jones R. N., Rudolph J. L., Yang F. M., Tommet D., Habtemariam D., et al.
(2010).  Development and Validation of a Brief Cognitive Assessment Tool: The Sweet 16.
Arch Intern Med. archinternmed.2010.423 - archinternmed.2010.423.

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DHA improves memory in older adults with cognitive impairment

December, 2010

A largish clinical study of cognitively impaired older adults has found six months of DHA supplements improved visual and verbal learning, though not working memory.

There have been mixed findings about the benefits of DHA (an omega-3 fatty acid), but in a study involving 485 older adults (55+) with age-related cognitive impairment, those randomly assigned to take DHA for six months improved the score on a visuospatial learning and episodic memory test. Higher levels of DHA in the blood correlated with better scores on the paired associate learning task. DHA supplementation was also associated with better verbal recognition, but not better working memory or executive function.

Other research has found no benefit from DHA to those already with Alzheimer’s, although those with Alzheimer’s tend to have lower levels of DHA in the blood. These findings reinforce the idea that the benefit of many proactive lifestyle strategies, such as diet and exercise, may depend mainly on their use before systems deteriorate.

The daily dose of algal DHA was 900 mg. The study took place at 19 clinical sites in the U.S., and those involved had an MMSE score greater than 26.

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Low testosterone linked to Alzheimer's disease

November, 2010

Another small study supports earlier research suggesting that low testosterone is a risk factor for Alzheimer’s for older men.

A Chinese study involving 153 older men (55+; average age 72), of whom 47 had mild cognitive impairment, has found that 10 of those in the MCI group developed probable Alzheimer's disease within a year. These men also had low testosterone, high blood pressure, and elevated levels of the ApoE4 protein.

The findings support earlier indications that low testosterone is associated with increased risk of Alzheimer's in men, but it’s interesting to note the combination with high blood pressure and having the ApoE4 gene. I look forward to a larger study.

Reference: 

Chu, L-W. et al. 2010. Bioavailable Testosterone Predicts a Lower Risk of Alzheimer’s Disease in Older Men. Journal of Alzheimer's Disease, 21 (4), 1335-45.

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Heavy smoking in midlife associated with dementia in later years

November, 2010

A very large long-running study has found smoking over two packs per day in middle age more than doubled the chances of developing dementia in later life.

Data from 21,123 people, surveyed between 1978 and 1985 when in their 50s and tracked for dementia from 1994 to 2008, has revealed that those who smoked more than two packs per day in middle age had more than twice the risk of developing dementia, both Alzheimer's and vascular dementia, compared to non-smokers.

A quarter of the participants (25.4%) were diagnosed with dementia during the 23 years follow-up, of whom a little over 20% were diagnosed with Alzheimer's disease and nearly 8% with vascular dementia.

Former smokers, or those who smoked less than half a pack per day, did not appear to be at increased risk. Associations between smoking and dementia did not vary by race or sex.

Smoking is a well-established risk factor for stroke, and is also known to contribute to oxidative stress and inflammation.

Reference: 

[1934] Rusanen, M., Kivipelto M., Quesenberry C. P., Zhou J., & Whitmer R. A.
(2010).  Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia.
Arch Intern Med. archinternmed.2010.393 - archinternmed.2010.393.

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