Small brain infarcts’ cognitive impact equals that of large infarct

Small infarct like brain lesions have long been ignored in both research and clinical setting, but on-going analysis of an observational cohort shows that they can be as cognitively damaging as large infarcts. Having both is a serious damaging one-two punch to thinking and memory.

At less than 3mm, infarct like lesions (ILL) may be tiny, but over 20 years, they exerted exactly the same deleterious effect on cognition as lesions 3mm or larger as said at the Alzheimer’s Association International Conference.

Patients who had both types of lesions declined cognitively much more than did those with just one type, whatever the size. The effect of having both types of lesions was equivalent to adding 27 more years of aging as said at the MIND Center Clinic at the University of Mississippi, Jackson. They think that it is a clear evidence that we should not continue to ignore these ILLs. It was already shown that they are important risk factor in stroke mortality. Now, we have pretty clear evidence that patients with them face the same cognitive decline risks as do those with large lesions and that patients with both types can experience significant cognitive decline over the years.

When neurologists began to look at brain infarcts several decades ago, they used then state-of-the-art 1.5 Tesla MRI. As infarct description and classification evolved, anything measuring smaller than 3mm was classified as infarct-like lesion and anything 3mm or larger as a large infarct. There was some concern that readers would confuse the ILLs with perivascular spaces and flag these normal voids as pathological changes. As a result, research studies have always excluded them. Since they are usually associated with silent events, without any clinical signs or symptoms, they’ve been clinically disregarded as well, adding to the perception that they have little long-term effect.

However, in 2015, a team proved this perception incorrect, at least when it came to stroke and stroke mortality. Using the large Atherosclerosis Risk in Communities (ARIC) Study cohort, they showed that ILL alone tripled the risk of both stroke and stroke mortality. Patients who had both ILLs and large infarcts were nine  more likely to have a stroke and seven times more likely to die from a stroke than were patients who had no lesions.

The same ARIC cohort was used in the 20-year cognition study. Begun in 1987, ARIC enrolled 15,800 middle-aged adults who had been followed regularly with physical and neurocognitive testing. Its goals are largely to investigate the natural history and multiple risk factors of cardiovascular and cerebrovascular disease. In 1993, subjects who had not experienced a stroke also had a brain MRI to add more detail to the study. The investigators also have performed cognitive assessments of a large number of participants five times since 1993 on measures of delayed world recall, digit symbol substitution, and world fluency. The outcome was the change in the composite Z score over time.

The cognition study comprise 1,881 to have brain MRI and the full five cognitive assessments over a 20-year period. The participants were stratified as having infarcts (1,611), only ILLs (50), large infarct (185), or both lesions (35).

At baseline, these subjects had a mean age of 63 years, 17 percent had diabetes, and 48 percent had hypertension. About one third were positive for an ApoE e4 allele. The mean white matter intensity score was 1.4.

In general, everyone in the cohort had some decline function as they got older. But striking observation was that those with ILLs only and those with large lesions only had virtually identical decline slopes over the 20-year follow-up. The change from baseline in global Z score was 0.18 standard deviation for the ILL only group and 0.24 standard deviation for the large infarct group. For those with both lesions, the change from baseline was 0.62.

At the end of 20 years, those with no lesions burden declined 1.3 standard deviation from baseline, those with only ILLs declined 1.5 standard deviation, and those with large infarct, 1.6 standard deviation. But, subjects who had both lesions declined 2.5 standard deviation from baseline. This is equivalent to adding 27 years of aging. The effect of having both was nearly four times greater than that of having only large lesions, which, up until now, have been the only ones read on MRI in either clinical practice or in research. Overall, our findings confirm that the relationship of ILLs to cognition is very similar to that of large infarcts.

The presence of midlife ILLs appears to amplify the effect of large infarct on cognition, and we hypothesize that this process may represent vascular disease at midlife.

We may also be able to identify people at high risk of cognitive decline or even dementia at midlife. I also think that we need to be rethinking how we read MRIs. Stopping at the 3-mm threshold may be too conservative. We should be looking at other studies on the consequences of these small lesions.