Health & age-related problems

What transient amnesia tells us about autobiographical memory and brain plasticity

November, 2011

Brain scans of those suffering from transient global amnesia indicate a permanent role of the hippocampus in autobiographical memory, and demonstrate the brain’s ability to self-repair.

When a middle-aged woman loses her memory after sex, it naturally makes the headlines. Many might equate this sort of headline to “Man marries alien”, but this is an example of a rare condition — temporary, you will be relieved to hear — known as transient global amnesia. Such abrupt, localized loss of autobiographical memory is usually preceded by strenuous physical activity or stressful events. It generally occurs in middle-aged or older adults, but has been known to occur in younger people. In those cases, there may be a history of migraine or head trauma.

Following an earlier study in which 29 of 41 TGA patients were found to have small lesions in the CA1 region of the hippocampus, scanning of another 16 TGA patients has revealed 14 had these same lesions. It seems likely that all the patients had such lesions, but because they are very small and don’t last long, they’re easy to miss. The lesion is best seen after 24-72 hours, but is gone after 5-6 days.

At the start of one of these attacks, memory for the first 30 years of life was significantly impaired, but still much better than memory for the years after that. There was a clear temporal gradient, with memory increasingly worse for events closer in time. There was no difference between events in the previous year and events in the previous five years, but a clear jump at that five-year point.

The exact location of the lesions was significant: when the lesion was in the anterior part of the region, memory for recent events was more impaired.

The hippocampus is known to be crucially involved in episodic memory (memory for events), and an integral part of the network for autobiographical memory. In recent years, it has come to be thought that such memories are only hosted temporarily by the hippocampus, and over a few years come to be permanently lodged in the neocortex (the standard consolidation model). Evidence from a number of studies of this change at the five-year mark has been taken as support for this theory. According to this, then, older memories should be safe from hippocampal damage.

An opposing theory, however, is that the hippocampus continues to be involved in such memories, with both the neocortex and the hippocampus involved in putting together reconsolidated memories (the multiple trace model). According to this model, each retrieval of an episodic memory creates a new version in the hippocampus. The more versions, the better protected a memory will be from any damage to the hippocampus.

The findings from this study show that while there is indeed a significant difference between older and more recent memories, the CA1 region of the hippocampus continues to be crucial for retrieving older memories, and for our sense of self-continuity.

Interestingly, some studies have also found a difference between the left and right hemispheres, with the right hippocampus showing a temporal gradient and the left hippocampus showing constant activation across all time periods. Such a hemisphere difference was not found in the present study. The researchers suggest that the reason may lie in the age of the participants (average age was 68), reflecting a reduction in hemispheric asymmetry with age.

There’s another message in this study. In these cases of TGA, memory function is restored within 24 hours (and generally sooner, within 6-10 hours). This shows how fast the brain can repair damage. Similarly, the fact that such tiny lesions have temporary effects so much more dramatic than the more lasting effects of larger lesions, is also a tribute to the plasticity of the brain.

The findings are consistent with findings of a preferential degeneration of CA1 neurons in the early stages of Alzheimer's disease, and suggest a target for treatment.

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Timing of estrogen therapy is crucial

October, 2011

A rat study provides further evidence that the conflicting findings on the benefit of estrogen therapy stem from the importance of timing.

The very large and long-running Women's Health Initiative study surprised everyone when it produced its finding that hormone therapy generally increased rather than decreased stroke risk as well as other health problems. But one explanation for that finding might be that many of the women only received hormone replacement therapy years after menopause. There are indications that timing is crucial.

This new rat study involved female rats equivalent to human 60-65 year olds, about a decade past menopause.  An enzyme called CHIP (carboxyl terminus of Hsc70 interacting protein) was found to increase binding with estrogen receptors, resulting in about half the receptors getting hauled to the cell's proteosome to be chopped up and degraded. When some of the aged rats were later treated with estrogen, mortality increased. When middle-aged rats were treated with estrogen, on the other hand, results were positive.

In other words, putting in extra estrogen after the number of estrogen receptors in the brain has been dramatically decreased is a bad idea.

While this study focused on mortality, other research has produced similar conflicting results as to whether estrogen therapy helps fight age-related cognitive impairment in women (see my report). It’s interesting to note that this effect only occurred in the hippocampus — estrogen receptors in the uterus were unaffected.

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Some cancer survivors can't shake foggy brain

July, 2011

For a minority of cancer survivors, cognitive problems will persist for years. Help with sleeping problems, and t’ai chi for stress release, may be beneficial.

A recent study of cancer survivors has found that many survivors still suffer moderate to severe problems with pain, fatigue, sleep, memory and concentration three to five years after treatment has ended.

The study included 248 survivors of breast, colorectal, lung and prostate cancer. The survivors were primarily female and white, and most were more than five years post-diagnosis. Cognitive difficulties were reported by 13%. The other most common symptoms were fatigue (16%), disturbed sleep (15%), and pain (13%). Two assessments were made, one month apart. The similar results indicate these symptoms tend to be chronic.

The researchers pointed to the need for education programs to help survivors transition from treatment to life as a cancer survivor, and the need for clinicians and researchers to develop better ways to address sleep problems, fatigue and lasting difficulties with memory and concentration.

One activity that could be part of a post-treatment program is t'ai chi.  A recent pilot study involving 23 women with a history of chemotherapy has found better cognitive and physical functioning after 10 weeks participating in a 60-minute t’ai chi class twice a week. Before and after the intervention, participants completed tests of memory, executive functioning, language, and attention, as well as tests of balance and self-report questionnaires of neuropsychological complaints, stress and mood, and fatigue.

However, though I’m a big fan of t’ai chi, I do have to note that without a control group, allowing the passing of time and the effects of any sort of group activity to be taken into account, it’s hard to draw any real conclusions from this.

Still, some support for this finding can be found in a recent meta-analysis of research investigating the benefits of t'ai chi for any improvement of medical conditions or clinical symptoms. This review found that the only clear evidence is in relation to fall prevention and improving psychological health. So, only middling support for t'ai chi, but the affirmation of its benefit for psychological health does support the potential value of this meditational practice for cancer survivors.

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The findings of the first study were presented June 4 at the 2011 American Society of Clinical Oncology Annual Meeting in Chicago.

[2320] Reid-Arndt SA, Matsuda S, Cox CR. Tai Chi effects on neuropsychological, emotional, and physical functioning following cancer treatment: A pilot study. Complementary Therapies in Clinical Practice [Internet]. Submitted ;In Press, Corrected Proof. Available from: http://www.sciencedirect.com/science/article/pii/S1744388111000259

[2319] Lee MS, Ernst E. Systematic reviews of t'ai chi: an overview. British Journal of Sports Medicine [Internet]. 2011 . Available from: http://bjsm.bmj.com/content/early/2011/05/02/bjsm.2010.080622.abstract

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Why it gets harder to remember as we get older

June, 2011

A new study finds that older adults have more difficulty in recognizing new information as ‘new’, and this is linked to degradation of the path leading into the hippocampus.

As we get older, when we suffer memory problems, we often laughingly talk about our brain being ‘full up’, with no room for more information. A new study suggests that in some sense (but not the direct one!) that’s true.

To make new memories, we need to recognize that they are new memories. That means we need to be able to distinguish between events, or objects, or people. We need to distinguish between them and representations already in our database.

We are all familiar with the experience of wondering if we’ve done something. Is it that we remember ourselves doing it today, or are we remembering a previous occasion? We go looking for the car in the wrong place because the memory of an earlier occasion has taken precedence over today’s event. As we age, we do get much more of this interference from older memories.

In a new study, the brains of 40 college students and older adults (60-80) were scanned while they viewed pictures of everyday objects and classified them as either "indoor" or "outdoor." Some of the pictures were similar but not identical, and others were very different. It was found that while the hippocampus of young students treated all the similar pictures as new, the hippocampus of older adults had more difficulty with this, requiring much more distinctiveness for a picture to be classified as new.

Later, the participants were presented with completely new pictures to classify, and then, only a few minutes later, shown another set of pictures and asked whether each item was "old," "new" or "similar." Older adults tended to have fewer 'similar' responses and more 'old' responses instead, indicating that they could not distinguish between similar items.

The inability to recognize information as "similar" to something seen recently is associated with “representational rigidity” in two areas of the hippocampus: the dentate gyrus and CA3 region. The brain scans from this study confirm this, and find that this rigidity is associated with changes in the dendrites of neurons in the dentate/CA3 areas, and impaired integrity of the perforant pathway — the main input path into the hippocampus, from the entorhinal cortex. The more degraded the pathway, the less likely the hippocampus is to store similar memories as distinct from old memories.

Apart from helping us understand the mechanisms of age-related cognitive decline, the findings also have implications for the treatment of Alzheimer’s. The hippocampus is one of the first brain regions to be affected by the disease. The researchers plan to conduct clinical trials in early Alzheimer's disease patients to investigate the effect of a drug on hippocampal function and pathway integrity.

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Temporary cognitive impairment for many hospitalized seniors

May, 2011

Hospitalization can temporarily impair seniors’ cognitive function, and more support is needed. Discharge instructions should be given with this in mind.

A study involving 200 older adults (70+) experiencing a stay in hospital has found that at discharge nearly a third (31.5%) had previously unrecognized low cognitive function (scoring below 25 on the MMSE if high-school-educated, or below 18 if not). This impairment had disappeared a month later for more than half (58%).The findings are consistent with previous research showing a lack of comprehension of discharge instructions, often resulting in rehospitalization.

The findings demonstrate the effects of hospitalization on seniors, and point to the need for healthcare professionals and family to offer additional support. It’s suggested that patient self-management may be better taught as an outpatient following discharge rather than at the time of hospital discharge.

Sleep disruption and stress are presumed to be significant factors in why this occurs.

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Sleep problems contribute to cognitive problems in childhood cancer survivors

May, 2011

Many survivors of childhood cancer suffer cognitive impairment in adulthood. A new study finds this is more likely for those with sleep or fatigue problems.

A study involving 1426 long-term survivors of childhood cancer (survivors of eight different childhood cancers who were treated between 1970 and 1986) has revealed cognitive impairment in over a fifth. Those who reported problems sleeping or frequent daytime sleepiness and fatigue were three to four times more likely to have attention and memory problems.

Additionally, those who were taking antidepressants were 50% more likely to report attention problems and 70% more likely to report memory problems.

The findings emphasize the need for help in sleep hygiene for this group.

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Brains of those with MCI still flexible and trainable

April, 2011

A small study demonstrates that mild cognitive impairment doesn’t preclude retraining the brain to find new ways to perform cognitive tasks.

A training program designed to help older adults with MCI develop memory strategies has found that their brains were still sufficiently flexible to learn new ways to compensate for impairment in some brain regions. The study involved 30 older adults, of whom 15 had MCI. Participants’ brains were scanned 6 weeks prior to memory training, one week prior to training and one week after training.

Before training, those with MCI showed less activity in brain regions associated with memory. After training they showed increased activation in these areas as well as in areas associated with language processing, spatial and object memory and skill learning. In particular, new activity in the right inferior parietal gyrus was associated with improvement on a memory task.

The findings demonstrate that even once diagnosed with MCI (a precursor to Alzheimer’s disease), brains can still be ‘rewired’ to use undamaged brain regions for tasks customarily done by now-damaged regions.

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Hippocampal volume and PTSD

April, 2011

A new study supports the association between hippocampal size and recovery from PTSD, pointing to the role of neurogenesis in stress resilience.

Following previous research suggesting that the volume of the hippocampus was reduced in some people with chronic PTSD, a twin study indicated that this may not be simply a sign that stress has shrunk the hippocampus, but that those with a smaller hippocampus are at greater risk of PTSD. Now a new study has found that Gulf War veterans who recovered from PTSD had, on average, larger hippocampi than veterans who still suffer from PTSD. Those who recovered had hippocampi of similar size to control subjects who had never had PTSD.

The study involved 244 Gulf War veterans, of whom 82 had lifetime PTSD, 44 had current PTSD, and 38 had current depression.

Because we don’t know hippocampal size prior to trauma, the findings don’t help us decide whether hippocampal size is a cause or an effect (or perhaps it would be truer to say, don’t help us decide the relative importance of these factors, because it seems most plausible that both are significant).

The really important question, of course, is whether an effective approach to PTSD treatment would be to work on increasing hippocampal volume. Exercise and mental stimulation, for example, are known to increase the creation of new brain cells in the hippocampus. In this case, the main mediator is probably the negative effects of stress (which reduces neurogenesis). There is some evidence that antidepressant treatment might increase hippocampal volume in people with PTSD.

The other conclusion we can derive from these findings is that perhaps we should not simply think of building hippocampal volume / creating new brain cells as a means of building cognitive reserve, thus protecting us from cognitive decline and dementia. We should also think of it as a means of improving our emotional resilience and protecting us from the negative effects of stress and trauma.

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Warm weather and marijuana impair cognition in people with MS

April, 2011

A recent study found significant cognitive impairment in MS sufferers who used marijuana for relief. Another study found cognition was better in MS sufferers on cooler days.

A study involving 50 people with MS (aged 18-65), of whom half used marijuana for pain relief, has found that marijuana users performed significantly worse on tests of attention, speed of thinking, executive function and visual perception of spatial relationships between objects. Those who used marijuana were also twice as likely as non-users to be classified as globally cognitively impaired.

The two groups were matched for age, gender, level of education, IQ before diagnosis, level of disability and duration of time with MS. On average, the duration of marijuana use was 26 years, and 72% reported smoking marijuana on a daily basis while 24% reported weekly use and one person reported bi-weekly use. There were no differences between the groups on measures of depression and anxiety.

And on a less-expected note, a study involving 40 people with multiple sclerosis and 40 people without MS has found those with MS scored 70% better on cognitive tests during cooler days compared to warmer days of the year. There was no link between test scores and temperature for those without MS.

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[2178] Honarmand K, Tierney MC, O'Connor P, Feinstein A. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology [Internet]. 2011 ;76(13):1153 - 1160. Available from: http://www.neurology.org/content/76/13/1153.abstract

The findings of the temperature study were presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

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Why multitasking is more difficult with age

April, 2011

A new study reveals that older adults’ greater problems with multitasking stem from their impaired ability to disengage from an interrupting task and restore the original task.

Comparison of young adults (mean age 24.5) and older adults (mean age 69.1) in a visual memory test involving multitasking has pinpointed the greater problems older adults have with multitasking. The study involved participants viewing a natural scene and maintaining it in mind for 14.4 seconds. In the middle of the maintenance period, an image of a face popped up and participants were asked to determine its sex and age. They were then asked to recall the original scene.

As expected, older people had more difficulty with this. Brain scans revealed that, for both groups, the interruption caused their brains to disengage from the network maintaining the memory and reallocate resources to processing the face. But the younger adults had no trouble disengaging from that task as soon as it was completed and re-establishing connection with the memory maintenance network, while the older adults failed both to disengage from the interruption and to reestablish the network associated with the disrupted memory.

This finding adds to the evidence that an important (perhaps the most important) reason for cognitive decline in older adults is a growing inability to inhibit processing, and extends the processes to which that applies.

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