Vascular Burden Predicts Gait, Mood, and Executive Function Disturbances in Older Adults with Mild Cognitive Impairment: Results from the Gait and Brain Study

To the Editor: Mild cognitive impairment (MCI) is a major health concern because of its high prevalence, affecting up to 20% of older adults,1-4 and one-third of people with MCI will convert to dementia, with progressive loss of function and autonomy.2 Vascular burden is known to promote the conversion of MCI to dementia.2-4 It has been suggested that vascular factors may cause a loss of cognitive and motor functions through brain damage, in particular in the frontal lobes.5, 6 Frontal lobe damage may be clinically expressed as frontal-subcortical dysfunctions, namely executive dysfunctions, gait disorders, and depression,5 although this triad of frontal-subcortical dysfunctions has not been specifically studied in people with MCI. We hypothesized that vascular burden could be responsible for cognitive, mobility, and mood disturbances in people with MCI. The objective of this cross-sectional study was to determine whether community-dwelling older adults with MCI and a high vascular burden were more likely to exhibit the frontal-subcortical triad of executive dysfunction, gait disorders, and depressive symptoms than those with a low vascular burden. Thirty-five participants with MCI from the Gait and Brain Study, a prospective ongoing cohort study in London, Ontario, Canada, designed to determine whether cognitive and gait impairments in older adults with MCI, as combined factors, can predict early conversion to dementia,7 were included in the present analysis. Identification of MCI was based on established consensus clinical criteria.1 Vascular burden was assessed using the Vascular Factors Index, a previously validated 7-point scale that includes vascular risk factors (hypertension, dyslipidemia, diabetes mellitus) and diseases (coronary artery disease, stroke, congestive heart failure, atrial fibrillation).2 High vascular burden was defined as the presence of at least two vascular factors. The triad of frontal-subcortical dysfunctions was defined as the presence of executive dysfunction, gait disorders, and depressive symptoms. Executive dysfunction was defined as being in the lowest tertile of a modified CLOX score (≤10). CLOX is a standardized quantitative method assessing executive function using the Clock Drawing Test.8 The CLOX score in the current sample ranged from 0 to 13 (lower scores reflect greater impairment). Gait disorders were defined as a gait velocity less than 100 cm/s.9 Gait velocity was collected during steady-state walking using an electronic portable walkway (GAITRite, 600 × 64 × 1 cm; CIR Systems, Havertown, PA). Depressive symptoms were defined as being in the highest tertile of the 15-item Geriatric Depression Scale score (in this sample, a score ≥3).10 Age and sex were considered as potential confounders. Between-group comparisons were performed using the chi-square or Student t-test, as appropriate. Multivariate analysis of variance (MANOVA) and multivariable linear and logistic regression analyses were performed to specify the associations between frontal-subcortical dysfunction and vascular burden (independent variable). P < .05 was considered statistically significant, and SPSS (version 19.0; SPSS, Inc., Chicago, IL) was used. Of 35 participants (mean age 75.5 ± 1.1; 57.1% female), 12 had at least two vascular factors. Table 1 shows that participants with two or more vascular factors had greater frontal-subcortical dysfunction (P = .006) and more often the complete triad (P = .04). MANOVA found an interaction between a high vascular burden, two or more vascular factors, and the three components of the triad considered as continuous dependent variables (F(3,35) = 3.25, P = .04, controlled for age and sex). Number of vascular factors was directly associated with number of frontal-subcortical dysfunctions (adjusted β = 0.30, 95% confidence interval (CI) = 0.08–0.52, P = .009). Vascular burden was associated with number of frontal-subcortical dysfunctions (adjusted β = 0.91, 95% CI = 0.29–1.53, P = .006) and with the finding of the complete triad (odds ratio = 2.62, 95% CI = 1.01–6.76, P = .047). These results show that vascular factors are prevalent in this cohort of MCI older adults, with one-third presenting having at least two vascular factors. To the best of our knowledge, this is the first study to demonstrate an association between vascular burden and frontal-subcortical dysfunctions in a population with MCI. These findings are consistent with the theory of the microvascular frontal-subcortical syndrome of aging,5 which argues that age-related vascular burden is responsible for frontal lobe dysfunction in older adults and subsequently results in geriatric syndromes of gait disorders, falls, depression, and dementia.2-6 The cross-sectional nature of the present analysis limits further interpretation of the associations and precludes causal inferences. The limited sample size precludes the comparison of the effects of the amnestic and nonamnestic subtypes of MCI. A future prospective analysis of this cohort should elucidate the role of frontal-subcortical dysfunction in MCI and determine whether older adults with MCI and frontal-subcortical dysfunction progress more or faster to dementia. Conflict of Interest: Dr. Montero-Odasso's program in Gait and Brain function is supported by grants from the Canadian Institutes for Health and Research—Institute of Aging, (CIHR-IA), the Drummond Foundation, the Physician Services Incorporated Foundation of Canada (PSI), the Lawson Health Research Institute, and the Ontario Ministry of Research and Innovation. He is a recipient of the Schulich Clinician-Scientist Award and the CIHR New Investigator Award. Dr. Annweiler served as an unpaid consultant for Ipsen Pharma company, is supported by a grant from the CIHR-IA, and holds a research grant from Servier Institute in France. Author Contributions: Dr. Montero-Odasso had full access to all of the data in the study; takes responsibility for the data, the analyses, and interpretation and the conduct of the research; and has the right to publish any and all data, separate and apart from the attitudes of the sponsor. All authors contributed toward conception and design, analyzing and interpreting data, drafting the article or revising it critically for important intellectual content, and approving the final version to be published. Sponsor's Role: None.