Memory problems in those with mild cognitive impairment may begin with problems in visual discrimination and vulnerability to interference — a hopeful discovery in that interventions to improve discriminability and reduce interference may have a flow-on effect to cognition.

The study compared the performance on a complex object discrimination task of 7 patients diagnosed with amnestic MCI, 10 older adults considered to be at risk for MCI (because of their scores on a cognitive test), and 19 age-matched controls. The task involved the side-by-side comparison of images of objects, with participants required to say, within 15 seconds, whether the two objects were the same or different.

In the high-interference condition, the objects were blob-like and presented as black and white line-drawings, with some comparison pairs identical, while others only varied slightly in either shape or fill pattern. Objects were rotated to discourage a simple feature-matching strategy. In the low-interference condition, these line-drawings were interspersed with color photos of everyday objects, for which discriminability was dramatically easier. The two conditions were interspersed by a short break, with the low interference condition run in two blocks, before and after the high interference condition.

A control task, in which the participants compared two squares that could vary in size, was run at the end.

The study found that those with MCI, as well as those at risk of MCI, performed significantly worse than the control group in the high-interference condition. There was no difference in performance between those with MCI and those at risk of MCI. Neither group was impaired in the first low-interference condition, although the at-risk group did show significant impairment in the second low-interference condition. It may be that they had trouble recovering from the high-interference experience. However, the degree of impairment was much less than it was in the high-interference condition. It’s also worth noting that the performance on this second low-interference task was, for all groups, notably higher than it was on the first low-interference task.

There was no difference between any of the groups on the control task, indicating that fatigue wasn’t a factor.

The interference task was specifically chosen as one that involved the perirhinal cortex, but not the hippocampus. The task requires the conjunction of features — that is, you need to be able to see the object as a whole (‘feature binding’), not simply match individual features. The control task, which required only the discrimination of a single feature, shows that MCI doesn’t interfere with this ability.

I do note that the amount of individual variability on the interference tasks was noticeably greater in the MCI group than the others. The MCI group was of course smaller than the other groups, but variability wasn’t any greater for this group in the control task. Presumably this variability reflects progression of the impairment, but it would be interesting to test this with a larger sample, and map performance on this task against other cognitive tasks.

Recent research has suggested that the perirhinal cortex may provide protection from visual interference by inhibiting lower-level features. The perirhinal cortex is strongly connected to the hippocampus and entorhinal cortex, two brain regions known to be affected very early in MCI and Alzheimer’s.

The findings are also consistent with other evidence that damage to the medial temporal lobe may impair memory by increasing vulnerability to interference. For example, one study has found that story recall was greatly improved in patients with MCI if they rested quietly in a dark room after hearing the story, rather than being occupied in other tasks.

There may be a working memory component to all this as well. Comparison of two objects does require shifting attention back and forth. This, however, is separate to what the researchers see as primary: a perceptual deficit.

All of this suggests that reducing “visual clutter” could help MCI patients with everyday tasks. For example, buttons on a telephone tend to be the same size and color, with the only difference lying in the numbers themselves. Perhaps those with MCI or early Alzheimer’s would be assisted by a phone with varying sized buttons and different colors.

The finding also raises the question: to what extent is the difficulty Alzheimer’s patients often have in recognizing a loved one’s face a discrimination problem rather than a memory problem?

Finally, the performance of the at-risk group — people who had no subjective concerns about their memory, but who scored below 26 on the MoCA (Montreal Cognitive Assessment — a brief screening tool for MCI) — suggests that vulnerability to visual interference is an early marker of cognitive impairment that may be useful in diagnosis. It’s worth noting that, across all groups, MoCA scores predicted performance on the high-interference task, but not on any of the other tasks.

So how much cognitive impairment rests on problems with interference?

HIV-associated dementia occurs in around 30% of untreated HIV-positive patients. Surprisingly, it also is occasionally found in some patients (2-3%) who are being successfully treated for HIV (and show no signs of AIDS).

A new study may have the answer for this mystery, and suggest a solution. Moreover, the answer may have general implications for those experiencing cognitive decline in old age.

The study found that HIV, although it doesn’t directly infect neurons, tries to stop the development of BDNF. Long known to be crucial for memory and learning, the reduced production of mature BDNF results in axons and dendrites shortening — meaning connections between neurons are lost. That in turn, brings about the death of some neurons.

It seems that the virus interferes with the normal process of development in BDNF, whereby one form of it, called proBDNF, is cut by certain enzymes into a new form called mature BDNF. It is in this form that it has its beneficial effect on neuron growth. Unfortunately, in its earlier form it is toxic to neurons.

This imbalance in the proportions of mature BDNF and proBDNF also appears to occur as we age, and in depression. It may also be a risk factor in Parkinson's and Huntington's diseases.

However, these findings suggest a new therapeutic approach.

Compounds in green tea and chocolate may help protect brain cells

In which context, it is interesting to note another new study, which has been busy analyzing the effects on brain cells of 2000 compounds, both natural and synthetic. Of the 256 that looked to have protective effects, nine were related to epicatechin, which is found in cocoa and green tea leaves.

While we’ve been aware for some time of these positive qualities, the study specifically identified epicatechin and epigallocatechin gallate (EGCG) as being the most effective at helping protect neurons by inducing production of BDNF.

One of the big advantages these compounds have is in their ability to cross the blood-brain barrier, making them a good candidate for therapy.

While green tea, dark chocolate, and cocoa are particularly good sources, many fruits also have good levels, in particular, black grapes, blackberries, apples, cherries, pears, and raspberries. (see this University of Davis document (pdf) for more detail)

Back in 2009, I reported briefly on a large Norwegian study that found that older adults who consumed chocolate, wine, and tea performed significantly better on cognitive tests. The association was assumed to be linked to the flavanols in these products. A new study confirms this finding, and extends it to older adults with mild cognitive impairment.

The study involved 90 older adults with MCI, who consumed either 990 milligrams, 520 mg, or 45 mg of a dairy-based cocoa drink daily for eight weeks. Their diet was restricted to eliminate other sources of flavanols (such as tea, red wine, apples and grapes).

Cognitive assessment at the end of this period revealed that, although scores on the MMSE were similar across all groups, those consuming higher levels of flavanol cocoa took significantly less time to complete Trail Making Tests A and B, and scored significantly higher on the verbal fluency test. Insulin resistance and blood pressure was also lower.

Those with the highest levels of flavanols did better than those on intermediate levels on the cognitive tests. Both did better than those on the lowest levels.

Changes in insulin resistance explained part, but not all, of the cognitive improvement.

One caveat: the group were generally in good health without known cardiovascular disease — thus, not completely representative of all those with MCI.

Adding to the growing evidence for the long-term cognitive benefits of childhood music training, a new study has found that even a few years of music training in childhood has long-lasting benefits for auditory discrimination.

The study involved 45 adults (aged 18-31), of whom 15 had no music training, 15 had one to five years of training, and 15 had six to eleven years. Participants were presented with different complex sounds ranging in pitch while brainstem activity was monitored.

Brainstem response to the sounds was significantly stronger in those with any sort of music training, compared to those who had never had any music training. This was a categorical difference — years of training didn’t make a difference (although some minimal length may be required — only one person had only one year of training). However, recency of training did make a difference to brainstem response, and it does seem that some fading might occur over long periods of time.

This difference in brainstem response means that those with music training are better at recognizing the fundamental frequency (lowest frequency sound). This explains why music training may help protect older adults from hearing difficulties — the ability to discriminate fundamental frequencies is crucial for understanding speech, and for processing sound in noisy environments.

I often talk about the importance of attitudes and beliefs for memory and cognition. A new honey bee study provides support for this in relation to the effects of aging on the brain, and suggests that this principle extends across the animal kingdom.

Previous research has shown that bees that stay in the nest and take care of the young remain mentally competent, but they don’t nurse for ever. When they’re older (after about 2-3 weeks), they become foragers, and foraging bees age very quickly — both physically and mentally. Obviously, you would think, bees ‘retire’ to foraging, and their old age is brief (they begin to show cognitive decline after just two weeks).

But it’s not as simple as that, because in artificial hives where worker bees are all the same age, nurse bees of the same age as foragers don’t show the same cognitive and sensory decline. Moreover, nurse bees have been found to maintain their cognitive abilities for more than 100 days, while foragers die within 18 days and show cognitive declines after 13-15 days (although their ability to assess sweetness remains intact).

The researchers accordingly asked a very interesting question: what happens if the foragers return to babysitting?

To achieve this, they removed all of the younger nurse bees from the nest, leaving only the queen and babies. When the older, foraging bees returned to the nest, activity slowed down for several days, and then they re-organized themselves: some of the old bees returned to foraging; others took on the babysitting and housekeeping duties (cleaning, building the comb, and tending to the queen). After 10 days, around half of these latter bees had significantly improved their ability to learn new things.

This cognitive improvement was also associated with a change in two specific proteins in their brains: one that has been associated with protection against oxidative stress and inflammation associated with Alzheimer disease and Huntington disease in humans (Prx6), and another dubbed a “chaperone” protein because it protects other proteins from being damaged when brain or other tissues are exposed to cell-level stress.

Precisely what it is about returning to the hive that produces this effect is a matter of speculation, but this finding does show that learning impairment in old bees can be reversed by changes in behavior, and this reversal is correlated with specific changes in brain protein.

Having said this, it shouldn’t be overlooked that only some of the worker bees showed this brain plasticity. This is not, apparently, due to differences in genotype, but may depend on the amount of foraging experience.

The findings add weight to the idea that social interventions can help our brains stay younger, and are consistent with growing evidence that, in humans, social engagement helps protect against dementia and age-related cognitive impairment.

The (probably) experience-dependent individual differences shown by the bees is perhaps mirrored in our idea of cognitive reserve, but with a twist. The concept of cognitive reserve emphasizes that accumulating a wealth of cognitive experience (whether through education or occupation or other activities) protects your brain from the damage that might occur with age. But perhaps (and I’m speculating now) we should also consider the other side of this: repeated engagement in routine or undemanding activities may have a deleterious effect, independent of and additional to the absence of more stimulating activities.