Shashank Shekhar, MD, MS

Sigurdsson S, Aspelund T, Kjartansson O, Gudmundsson EF, Jonsdottir MK, Eiriksdottir G, et al. Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study). Stroke. 2017

The recent published longitudinal study by Sigurdsson and colleagues highlights the types of infarction that are associated with cognitive decline, as well as the sex factor that can contribute to dementia after ischemic strokes.

This study is based on the longitudinal data gathered from an Icelandic population-based cohort of men and women from 2002 to 2006, in which 5764 participants were examined. A total of 3316 patients were followed up from 2007 to 2011. The study utilized the MRI to get the baseline and follow-up imaging to define the location of the stroke. All types of infarcts were included and categorized into Cortical infarcts, subcortical infarcts, and cerebellar infarction. Of 3316 participants from the follow-up, 2612 participants (1070 male and 1542 female) were included. Rejection of the rest was based on exclusion criteria. Cognition was assessed regarding memory, processing speed, and executive function. The cognitive screening was done with mini-mental and digital symbol substitution test and later confirmed using a diagnostic battery of neuropsychological tests. For each infarction type, the sample was categorized into four groups based on a combination of incidence and prevalence to find gender-based differences.

The result showed an overall 31% of infarction prevalence using MRI, but only 5.4% of those had a clinical event. The group with ≥1 prevalence or incidence were older regardless of sex when compared to no infarction group. Males, however, had a higher occurrence of comorbidities, lower relative brain volume and cognitive scores in all domains (age-adjusted P <0.05) than female. The sex difference in the incidence of infarction was double in males as compared to female. On cognitive assessment, males with both incidence and prevalent infarcts had steeper cognitive decline compared to no infarcts. The risk of dementia was higher with incident infarction or both prevalence and incidence infarction. Based on location, a person with incident subcortical infarction had 2.6 times risk of dementia, whereas cerebellar had the lowest risk of dementia than a person without infection. Additionally, after adjusting for age, the male had overall 1.8 times higher risk (2.9 times in cortical) of incident dementia than female. There was a general trend towards decline in memory, executive function, and processing speed in both genders from baseline to follow-up. Sex, per se, did not have any difference between overall infarct and incident dementia.

Use of MRI imaging to study the sex difference in the incidence of dementia based location is unique to this study. The strength of this study lies in a large number of cohort subjects with a higher number of incidence, however, somewhat underrating the prevalence of infarction in the population. One of the highlights of this study is the cognitive decline associated with increasing overall infarct load, a finding which is prominent in the male sex. The results of this study could be explained via the different pathological mechanism. One of the current hypotheses involves an impairment of vascular autoregulatory vascular pathway which could result in higher rate of stroke and eventually cognitive impairment. The neurovascular autoregulatory mechanism is modulated by endogenous sex hormones, particularly estrogen, which tends to have a protective effect on vessels of young females, making them less prone to strokes and dementia. Males, however, lack this protection mechanism, a finding consistent with the results here. This study does mention the difference in cognition based on locations. The steeper decline in cognition is reportedly more noticeable with subcortical infarcts, suggesting a cascade of a pathologic process affecting subcortical vessels more than large vessels.

This study, however, did not comment on the effects of single strategic infarction where a small lesion which is predominantly in subcortical areas if present could result in devastating cognitive impairment. The author shows the importance of gender, as well as the location of infarction, in development of dementia and concludes that subcortical infarction contributes more to the development of dementia. Future studies should study the implications of hormonal changes, as well as develop diagnostic criteria to diagnose and treat vascular-related dementia.