Health & age-related problems

Mild Cognitive Impairment

Except in the cases of stroke or traumatic brain injury, loss of cognitive function is not something that happens all at once. Cognitive impairment that comes with age may be thought of as belonging on a continuum, with one end being no cognitive impairment and the other end being dementia, of which Alzheimer's is the most common type.

Most older adults are actually at the "no impairment" end of the continuum. A further 30-40% of adults over 65 will have what is called "age-related memory impairment", which is the type of cognitive loss we regard as a normal consequence of age -- a measurable (but slight) decline on memory tests; a feeling that you're not quite as sharp or as good at remembering, as you used to be.

Only about 1% of these people will develop Alzheimer's.

But around 10% of adults over 65 develop "mild cognitive impairment", and this is a precursor of Alzheimer's. This doesn't mean someone with MCI will inevitably get Alzheimer's in their lifetime, but their likelihood of doing so is substantially increased.

Whether you are one of those 10% depends in part on your age and your level of education. A study2 of nearly 4000 people from the general population of a Minnesota county, run by the Mayo Clinic, indicates 9% of those aged 70 to 79 and nearly 18% of those 80 to 89 have MCI. The prevalence decreased with years of education: it was 25% in those with up to eight years of education, 14% in those with nine to 12 years, 9% in those with 13 to 16 years, and 8.5% in those with greater than 16 years.

Whether or not this will develop into Alzheimer’s can be predicted with a reasonably high level of accuracy (75%) by the rate at which brain tissue is being lost, and in particular the rate at which it is being lost in the hippocampus (arguably the most important region for memory in the brain). Whether actions known to build brain tissue (physical exercise, mental stimulation) can counteract that in this population is not yet known — but it certainly can’t hurt!

Mild cognitive impairment doesn’t necessarily mean memory problems. There are two types of MCI: those with the amnesic subtype (MCI-A) have memory impairments only, while those with the multiple cognitive domain subtype (MCI-MCD) have other types of mild impairments, such as in judgment or language, and mild or no memory loss. Both sub-types progress to Alzheimer's disease at the same rate, but they do have different pathologies in the brain.

Mild cognitive impairment is not necessarily obvious to outside observers. A person with it can function perfectly well, and although they may feel their impairment is obvious to all around them, it's not likely to be obvious to anyone not living with them.

A person suffering from mild cognitive impairment may find that they have problems with:

  • finding the right words
  • making decisions
  • remembering recent events
  • placing things in space (for example, getting the proportions right when drawing a simple object such as a box).

Essentially, age-related cognitive impairment might be thought of as slight, non-important, cognitive impairment, while mild cognitive impairment is a condition where significant cognitive impairment exists which nevertheless doesn't affect daily functioning. Dementia is significant cognitive impairment that does interfere with daily life.

References: 
  1. Becker, J.T. et al. 2006. Three-dimensional Patterns of Hippocampal Atrophy in Mild Cognitive Impairment. Archives of Neurology, 63, 97-101.
  2. Petersen, R. et al. 2006. Study presented April 4 at the American Academy of Neurology meeting in San Diego. Press release
  3. Quinn, J.F. & Kaye, J.A. 2004. Study presented at the 56th annual meeting of the American Academy of Neurology in San Francisco. Press release
  4. Small, G.W. 2002.What we need to know about age related memory loss. British Medical Journal, 324, 1502-1505.

Concussions in high school athletes may need longer recovery & better testing

Two small studies suggest that standard testing of concussed high school athletes might be insufficiently sensitive.

I’ve talked before about how even mild head injuries can have serious consequences, and in recent years we’ve seen growing awareness of the long-term dangers of sports’ concussions (especially for young people). This has been followed by a number of initiatives to help protect athletes. However, while encouraging, they may still be under-estimating the problem. Two recent studies, involving high school athletes who had experienced concussions, point to quite subtle impairment lasting for longer than expected.

In one study, 20 concussed adolescents were tested on their attention and executive function within 72 hours post injury, and then again at one week, two weeks, one month, and two months post injury. Compared with matched controls, they had a significantly greater switch cost on the Task-Switching Test and a significantly greater reaction time for the Attentional Network Test conflict effect component, with this lasting up to two months after injury.

The results suggest that longer recovery periods than the standard 7-10 days may be warranted, given that the slower reaction times (although only a matter of milliseconds) might make further injury more likely.

In another study, 54 adolescent athletes who had been concussed but who reported being symptom-free and had returned to baseline neurocognitive-test levels, were given, further testing. This revealed that over a quarter of them (27.7%) showed cognitive impairment following moderate physical exertion (15 to 25 minutes on a treadmill, elliptical, or stationary bicycle). These athletes scored significantly lower on verbal and visual memory, although processing speed and reaction was not affected (suggesting that tests focusing mainly on these latter abilities are insufficient).

The group affected did not differ from the rest in terms of symptoms or concussion history.

The findings suggest that computerized neurocognitive testing following moderate exertion should be part of the standard procedure when making return-to-play decisions.

Early surgical menopause linked to faster cognitive decline

Women who undergo surgical menopause at an earlier age may have an increased risk of cognitive decline.

The issue of the effect of menopause on women’s cognition, and whether hormone therapy helps older women fight cognitive decline and dementia, has been a murky one. Increasing evidence suggests that the timing and type of therapy is critical. A new study makes clear that we also need to distinguish between women who experience early surgical menopause and those who experience natural menopause.

The study involved 1,837 women (aged 53-100), of whom 33% had undergone surgical menopause (removal of both ovaries before natural menopause). For these women, earlier age of the procedure was associated with a faster decline in semantic and episodic memory, as well as overall cognition. The results stayed the same after factors such as age, education and smoking were taken into consideration.

There was also a significant association between age at surgical menopause and the plaques characteristic of Alzheimer's disease. However, there was no significant association with Alzheimer’s itself.

On the positive side, hormone replacement therapy was found to help protect those who had surgical menopause, with duration of therapy linked to a significantly slower decline in overall cognition.

Also positively, age at natural menopause was not found to be associated with rate of cognitive decline.

Reference: 

Bove, R. et al. 2013. Early Surgical Menopause Is Associated with a Spectrum of Cognitive Decline. To be presented at the American Academy of Neurology's 65th Annual Meeting in San Diego, March 21, 2013.

Worry & fatigue main reason for ‘chemo-brain’?

A new study points to pre-treatment reasons for declined cognitive function following chemotherapy, and suggests that anxiety may be the main driver.

The issue of ‘chemo-brain’ — cognitive impairment following chemotherapy — has been a controversial one. While it is now (I hope) accepted by most that it is, indeed, a real issue, there is still an ongoing debate over whether the main cause is really the chemotherapy. A new study adds to the debate.

The study involved 28 women who received adjuvant chemotherapy for breast cancer, 37 who received radiotherapy, and 32 age-matched healthy controls. Brain scans while doing a verbal working memory task were taken before treatment and one month after treatment.

Women who underwent chemotherapy performed less accurately on the working memory task both before treatment and one month after treatment. They also reported a significantly higher level of fatigue. Greater fatigue correlated with poorer test performance and more cognitive problems, across both patient groups and at both times (although the correlation was stronger after treatment).

Both patient groups showed reduced function in the left inferior frontal gyrus, before therapy, but those awaiting chemotherapy showed greater impairment than those in the radiotherapy group. Pre-treatment difficulty in recruiting this brain region in high demand situations was associated with greater fatigue after treatment.

In other words, reduced working memory function before treatment began predicted how tired people felt after treatment, and how much their cognitive performance suffered. All of which suggests it is not the treatment itself that is the main problem.

But the fact that reduced working memory function precedes the fatigue indicates it’s not the fatigue that’s the main problem either. The researchers suggest that the main driver is level of worry —worry interfered with the task; level of worry was related to fatigue. And worry, as we know, can reduce working memory capacity (because it uses up part of it).

All of which is to say that support for cancer patients aimed at combating stress and anxiety might do more for ‘chemo-brain’ than anything else. In this context, I note also that there have been suggestions that sleep problems have also been linked to chemo-brain — a not unrelated issue!

Reference: 

Cimprich, B. et al. 2012. Neurocognitive impact in adjuvant chemotherapy for breast cancer linked to fatigue: A Prospective functional MRI study. Presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, Dec. 4-8

Caffeine may block inflammation linked to cognitive impairment

A mouse study indicates that caffeine can help prevent inflammation occurring in the brain, by blocking an early response to cell damage.

Caffeine has been associated with a lower of developing Alzheimer's disease in some recent studies. A recent human study suggested that the reason lies in its effect on proteins involved in inflammation. A new mouse study provides more support for this idea.

In the study, two groups of mice, one of which had been given caffeine, were exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow. When re-oxygenated, caffeine-treated mice recovered their ability to form a new memory 33% faster than the other mice, and the caffeine was observed to have the same anti-inflammatory effect as blocking interleukin-1 (IL-1) signaling.

Inflammation is a key player in cognitive impairment, and IL-1 has been shown to play a critical role in the inflammation associated with many neurodegenerative diseases.

It was found that the hypoxic episode triggered the release of adenosine, the main component of ATP (your neurons’ fuel). Adenosine is released when a cell is damaged, and this leakage into the environment outside the cell begins a cascade that leads to inflammation (the adenosine activates an enzyme, caspase-1, which triggers production of the cytokine IL-1β).

But caffeine blocks adenosine receptors, stopping the cascade before it starts.

The finding gives support to the idea that caffeine may help prevent cognitive decline and impairment.

Brain training helps cognitive decline in many cancer survivors

A pilot study found that both training in memory strategies and processing speed training had significant benefits for breast cancer survivors with concerns about their memory and cognition.

Cancer survivors who underwent chemotherapy often suffer long-term cognitive problems. Until now, most research has been occupied with establishing that this is in fact the case, and studies investigating how to help have been rare. I recently reported on studies suggesting that help with sleep problems and stress can be beneficial. It has also been suggested that exercise can help. None of these suggestions are special to cancer survivors (although cancer survivors may well be one of several groups that derive particular benefit). Similarly, a new study investigates another familiar approach to improving cognitive decline.

The pilot study involved 82 post-menopausal breast cancer survivors (average age 56) who had received chemotherapy and who were worried about their cognitive abilities. The women were randomly assigned to one of three groups: one group received memory training adapted from the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) trial; another received processing speed training using Posit Science’s Insight program (commercially available); the third was a wait-listed control group.

Training consisted of ten 1-hour small-group (3-5 people) sessions over 6-8 weeks. Memory training involved learning strategies and applying them to word lists, sequences, and texts. Strategies included mnemonic techniques, as well as instruction in principles of meaningfulness, organization, visualization, and association. Strategies were taught and practiced in the first five sessions, and further practiced in the remaining sessions.

In the Insight program, stimulus duration is progressively shortened during a series of progressively more difficult information-processing tasks, such as time-order judgment, discrimination, spatial-match, forward-span, instruction-following, and narrative-memory tasks. Exercises automatically adjust to maintain an 85% correct rate.

Both programs proved beneficial. The memory training group showed significant improvement in immediate and delayed memory, which was maintained at the two-month follow-up. There was of course individual variability: 39% showed significant improvement on immediate memory (compared to 18% of controls) and 42% on delayed memory (compared to 11% of controls). While the group as a whole didn’t show significant improvement in processing speed, some 73% of the group showed reliable improvement at the two-month follow-up.

The Insight group showed significant improvement on both memory and processing speed. Some 68% improved processing speed (compared to 43% of controls). But note that at the 2-month follow-up, the 67% of the Insight group is not that much greater than the 61% of the controls (demonstrating very clearly the benefits of even the small amount of practice received in testing) and is in fact less than the 73% of the memory group.

The Insight group also showed significant improvement in memory. At two-month follow-up, some 30% of the Insight group had improved immediate memory (compared to the 18% of controls), and 33% had improved delayed memory (vs 11%).

Both training programs had a positive effect on perceived cognitive functioning and symptom distress (mood, anxiety, fatigue), and there was no difference between the groups in terms of satisfaction with the training (both groups were very satisfied).

The researchers concluded that, while both training programs were promising, the dual effect of processing speed training (on memory as well as processing speed) argued for its broader benefits.

However, I note that, although the size of the effect of memory training on processing speed was too small to reach statistical significance, the fact that the number of participants showing reliable improvement was greater than that of the Insight group points to an equally broad effect of memory training. If the memory training was supplemented by a small amount of practice on tasks designed to boost processing speed, it would seem to me that this might produce greater cognitive benefits than the processing speed training. Indeed, the Insight program was, I believe, first developed in the context of the ACTIVE program, and I have, of course, talked before about the value of training that includes multiple domains.

Still, the main message of this study should not be overlooked: it demonstrates that many cancer survivors suffering from cognitive decline can improve their cognitive performance through training and practice.

Improving memory for specific events can help depression

A small study suggests that training in recalling personal memories can significantly help those with depression.

We know that people with depression tend to focus on, and remember, negative memories rather than positive. Interestingly, it’s not simply an emotion effect. People with depression, and even those at risk of depression (including those who have had depression), tend to have trouble remembering specific autobiographical memories. That is, memories of events that happened to them at a specific place and time (as opposed to those generalized event memories we construct from similar events, such as the ‘going to the dentist’ memory).

This cognitive difficulty seems to exacerbate their depression, probably through its effect on social encounters and relationships.

A new study, however, has found that a particular training program (“Memory Specificity Training”) can help both their memory for specific events and their symptoms of depression.

The study involved 23 adolescent Afghani refugees in Iran, all of whom had lost their fathers in the war in Afghanistan and who showed symptoms of depression. Half were randomly assigned to the five-week memory training program and half received no training.

The training program involved a weekly 80-minute group session, in which participants learned about different types of memory and memory recall, and practiced recalling specific memories after being given positive, neutral, and negative keywords.

Participants’ memory for specific events was tested at the start of the study, at the end of the five-week training period, and two months after the end of the training. Compared to the control group, those given the training were able to provide more specific memories after the training, and showed fewer symptoms of depression at the two month follow-up (but not immediately after the end of training).

The study follows on from a pilot study in which ten depressed female patients were given four weekly one-hour sessions of memory training. Improvements in memory retrieval were associated with less rumination (dwelling on things), less cognitive avoidance, and improvements in problem-solving skills.

It’s somewhat unfortunate that the control group were given no group sessions, indeed no contact (apart from the tests) of any kind. Nevertheless, and bearing in mind that these are still very small studies, the findings do suggest that it would be helpful to include a component on memory training in any cognitive behavioral therapy for depression.

Immune system may protect against Alzheimer's

New studies involving genetically-engineered mice and older adult humans support a connection between the immune system and cognitive impairment in old age.

A number of studies have come out in recent years linking age-related cognitive decline and dementia risk to inflammation and infection (put inflammation into the “Search this site” box at the top of the page and you’ll see what I mean). New research suggests one important mechanism.

In a mouse study, mice engineered to be deficient in receptors for the CCR2 gene — a crucial element in removing beta-amyloid and also important for neurogenesis — developed Alzheimer’s-like pathology more quickly. When these mice had CCR2 expression boosted, accumulation of beta-amyloid decreased and the mice’s memory improved.

In the human study, the expression levels of thousands of genes from 691 older adults (average age 73) in Italy (part of the long-running InCHIANTI study) were analyzed. Both cognitive performance and cognitive decline over 9 years (according to MMSE scores) were significantly associated with the expression of this same gene. That is, greater CCR2 activity was associated with lower cognitive scores and greater decline.

Expression of the CCR2 gene was also positively associated with the Alzheimer’s gene — meaning that those who carry the APOE4 variant are more likely to have higher CCR2 activity.

The finding adds yet more weight to the importance of preventing / treating inflammation and infection.

Reference: 

[2960] Harries, L. W., Bradley-Smith R. M., Llewellyn D. J., Pilling L. C., Fellows A., Henley W., et al. (2012).  Leukocyte CCR2 Expression Is Associated with Mini-Mental State Examination Score in Older Adults. Rejuvenation Research. 120518094735004 - 120518094735004.

Naert, G. & Rivest S. 2012. Hematopoietic CC-chemokine receptor 2-(CCR2) competent cells are protective for the cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease. Molecular Medicine, 18(1), 297-313.

El Khoury J, et al. 2007. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Medicine, 13, 432–8.

Working with solvents linked to cognitive problems in less-educated people

A study qualifies evidence that occupational exposure to solvents increases the risk of cognitive impairment later in life.

The study involved 4,134 people (average age 59) who worked at the French national gas and electric company, of whom most worked at the company for their entire career. Their lifetime exposure to chlorinated solvents, petroleum solvents, benzene and non-benzene aromatic solvents was estimated, and they were given the Digit Symbol Substitution Test to assess cognitive performance. Cognitive impairment was defined as scoring below the 25th percentile. Most of the participants (88%) were retired.

For analysis, participants were divided into two groups based on whether they had less than a secondary school education or not. This revealed an interesting finding: higher rates of solvent exposure were associated with cognitive impairment, in a dose-dependent relationship — but only in those with less than a high school education. Recency of solvent exposure also predicted worse cognition among the less-educated (suggesting that at least some of the damage was recoverable).

However, among those with secondary education or higher, there was no significant association between solvent exposure (quantity or recency) and cognition.

Over half the participants (58%) had less than a high school education. Of those, 32% had cognitive impairment — twice the rate in those with more education.

The type of solvent also made a difference, with non-benzene aromatic solvents the most dangerous, followed by benzene solvents, and then chlorinated and petroleum solvents (the rates of cognitive impairment among highly-exposed less-educated, was 36%, 24%, and 14%, respectively).

The findings point to the value of cognitive reserve, but I have several caveats. (Unfortunately, this study appears in a journal to which I don’t have access, so it’s possible the first of this at least is answered in the paper.) The first is that those with less education had higher rates of exposure, which raises the question of a threshold effect. Second is that the cognitive assessment is only at one point of time, lacking both a baseline (do we know what sort of average score adults of this age and with this little education would achieve? A quick online search threw up no such appropriate normative data) and a time-comparison that would give a rate of decline. Third, is that the cognitive assessment is very limited, being based on only one test.

In other words, the failure to find an effect among those with at least a high school education may well reflect the lack of sensitivity in the test (designed to assess brain damage). More sensitive tests, and test comparisons over time, may well give a different answer.

On its own, then, this finding is merely another data-point. But accumulating data-points is how we do science! Hopefully, in due course there’ll be a follow-up that will give us more information.

Eye health related to brain health in older adults

A large, long-running study has found cognitive decline and brain lesions are linked to mild retinal damage in older women.

Damage to the retina (retinopathy) doesn’t produce noticeable symptoms in the early stages, but a new study indicates it may be a symptom of more widespread damage. In the ten-year study, involving 511 older women (average age 69), 7.6% (39) were found to have retinopathy. These women tended to have lower cognitive performance, and brain scans revealed that they had more areas of small vascular damage within the brain — 47% more overall, and 68% more in the parietal lobe specifically. They also had more white matter damage. They did not have any more brain atrophy.

These correlations remained after high blood pressure and diabetes (the two major risk factors for retinopathy) were taken into account. It’s estimated that 40-45% of those with diabetes have retinopathy.

Those with retinopathy performed similarly to those without on a visual acuity test. However, testing for retinopathy is a simple test that should routinely be carried out by an optometrist in older adults, or those with diabetes or hypertension.

The findings suggest that eye screening could identify developing vascular damage in the brain, enabling lifestyle or drug interventions to begin earlier, when they could do most good. The findings also add to the reasons why you shouldn’t ignore pre-hypertensive and pre-diabetic conditions.

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