Providing some support for the finding I recently reported — that problems with semantic knowledge in those with mild cognitive impairment (MCI) and Alzheimer’s might be rooted in an inability to inhibit immediate perceptual information in favor of conceptual information — a small study has found that executive function (and inhibitory control in particular) is impaired in far more of those with MCI than was previously thought.

The study involved 40 patients with amnestic MCI (single or multiple domain) and 32 healthy older adults. Executive function was tested across multiple sub-domains: divided attention, working memory, inhibitory control, verbal fluency, and planning.

As a group, those with MCI performed significantly more poorly in all 5 sub-domains. All MCI patients showed significant impairment in at least one sub-domain of executive functioning, with almost half performing poorly on all of the tests. The sub-domain most frequently and severely impaired was inhibitory control.

The finding is in sharp contrast with standard screening tests and clinical interviews, which have estimated executive function impairment in only 15% of those with MCI.

Executive function is crucial for many aspects of our behavior, from planning and organization to self-control to (as we saw in the previous news report) basic knowledge. It is increasingly believed that inhibitory control might be a principal cause of age-related cognitive decline, through its effect on working memory.

All this adds weight to the idea that we should be focusing our attention on ways to improve inhibitory control when it declines. Although training to improve working memory capacity has not been very successful, specific training targeted at inhibitory control might have more luck. Something to hope for!

Sad to say, another large study has given the thumbs down to ginkgo biloba preventing Alzheimer’s disease.

The randomized, double-blind trial took place over five years, involving 2854 older adults (70+) who had presented to their primary care physician with memory complaints. Half were given a twice-daily dose of 120 mg standardised ginkgo biloba extract and half a placebo.

After five years, 4% of those receiving ginkgo biloba had been diagnosed with probable Alzheimer's disease, compared with 5% in the placebo group — an insignificant difference. There was no significant difference between the groups in mortality, stroke, or cardiovascular events, either.

The French study confirms the findings of an earlier American trial, and is also consistent with another large, long-running study that found no benefits of ginkgo biloba for age-related cognitive decline.

A small study shows how those on the road to Alzheimer’s show early semantic problems long before memory problems arise, and that such problems can affect daily life.

The study compared 25 patients with amnestic MCI, 27 patients with mild-to-moderate Alzheimer's and 70 cognitively fit older adults (aged 55-90), on a non-verbal task involving size differences (for example, “What is bigger: a key or a house?”; “What is bigger: a key or an ant?”). The comparisons were presented in three different ways: as words; as images reflecting real-world differences; as incongruent images (e.g., a big ant and a small house).

Both those with MCI and those with AD were significantly less accurate, and significantly slower, in all three conditions compared to healthy controls, and they had disproportionately more difficulty on those comparisons where the size distance was smaller. But MCI and AD patients experienced their biggest problems when the images were incongruent – the ant bigger than the house. Those with MCI performed at a level between that of healthy controls and those with AD.

This suggests that perceptual information is having undue influence in a judgment task that requires conceptual knowledge.

Because semantic memory is organized according to relatedness, and because this sort of basic information has been acquired a long time ago, this simple test is quite a good way to test semantic knowledge. As previous research has indicated, the problem doesn’t seem to be a memory (retrieval) one, but one reflecting an actual loss or corruption of semantic knowledge. But perhaps, rather than a loss of data, it reflects a failure of selective attention/inhibition — an inability to inhibit immediate perceptual information in favor of more relevant conceptual information.

How much does this matter? Poor performance on the semantic distance task correlated with impaired ability to perform everyday tasks, accounting (together with delayed recall) for some 35% of the variance in scores on this task — while other cognitive abilities such as processing speed, executive function, verbal fluency, naming, did not have a significant effect. Everyday functional capacity was assessed using a short form of the UCSD Skills Performance Assessment scale (a tool generally used to identify everyday problems in patients with schizophrenia), which presents scenarios such as planning a trip to the beach, determining a route, dialing a telephone number, and writing a check.

The finding indicates that semantic memory problems are starting to occur early in the deterioration, and may be affecting general cognitive decline. However, if the problems reflect an access difficulty rather than data loss, it may be possible to strengthen these semantic processing connections through training — and thus improve general cognitive processing (and ability to perform everyday tasks).

It’s been unclear whether hormone therapy helps older women reduce their risk of Alzheimer’s or in fact increases the risk. To date, the research has been inconsistent, with observational studies showing a reduced risk, and a large randomized controlled trial showed an increased risk. As mentioned before, the answer to the inconsistency may lie in the timing of the therapy. A new study supports this view.

The 11-year study (part of the Cache County Study) involved 1,768 older women (65+), of whom 1,105 women had used hormone therapy (either estrogen alone or in combination with a progestin). During the study, 176 women developed Alzheimer's disease. This included 87 (7.9%) of the 1,105 women who had taken hormone therapy, and 89 (13.4%) of the 663 others.

Women who began hormone therapy, of any kind, within five years of menopause had a 30% lower risk of developing Alzheimer's within the study period (especially if they continued the therapy for 10 or more years). Those who began treatment more than five years after menopause, had a ‘normal’ risk (i.e., not reduced or increased). However, those who had started a combined therapy of estrogen and progestin when they were at least 65 years old had a significantly higher risk of developing Alzheimer’s.

The findings support the idea that the timing of hormone therapy, and the type, are critical factors, although the researchers cautiously note that more research is needed before they can make new clinical recommendations.

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?