White Matter Microstructural Damage in Small Vessel Disease Is Associated With Montreal Cognitive Assessment But Not With Mini Mental State Examination Performances
Vascular Mild Cognitive Impairment Tuscany Study
Background and Purpose—Montreal Cognitive Assessment (MoCA) has been proposed as a screening tool in vascular cognitive impairment. Diffusion tensor imaging is sensitive to white matter microstructural damage. We investigated if diffusion tensor imaging-derived indices are more strongly associated with performances on MoCA or on the widely used mini mental state examination in patients with mild cognitive impairment and small vessel disease.
Methods—Mild cognitive impairment patients with moderate/severe degrees of white matter hyperintensities on MRI were enrolled. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy and median values of mean diffusivity and fractional anisotropy of the cerebral white matter were studied and correlated with cognitive tests performances.
Results—Seventy-six patients (mean age 75.1±6.8 years, mean years of education 8.0±4.3) were assessed. In univariate analyses, a significant association of both MoCA and mini mental state examination scores with age, education, cortical atrophy, and medial temporal lobe atrophy was found, whereas mean diffusivity and fractional anisotropy were associated with MoCA. In partial correlation analyses, adjusting for all demographic and neuroimaging variables, both mean diffusivity and fractional anisotropy were associated only with MoCA (mean diffusivity: r= −0.275, P=0.023; fractional anisotropy: r=0.246, P=0.043).
Conclusions—In patients with mild cognitive impairment and small vessel disease, diffusion tensor imaging-measured white matter microstructural damage is more related to MoCA than mini mental state examination performances. MoCA is suited for the cognitive screening of patients with small vessel disease.
Montreal Cognitive Assessment (MoCA) has been proposed as a screening tool in vascular cognitive impairment because, differently from the widely used mini mental state examination (MMSE), it includes attentional, psychomotor speed, and executive tasks.3–6
Diffusion tensor imaging (DTI) is an MRI technique able to detect changes in white matter microstructure that are not evidenced on conventional MRI, but may have a clinical effect.7
We assessed whether white matter microstructural damage as measured with DTI in patients with mild cognitive impairment (MCI) and SVD is more strongly reflected by MoCA than MMSE performances. If this holds true, it would support the hypothesis that MoCA is more suited than MMSE as a cognitive screening tool to assess patients with MCI related to SVD.
The Vascular Mild Cognitive Impairment Tuscany (VMCI-Tuscany) study is a multicenter, prospective, observational study designed to estimate the effect of a large set of clinical, neuroimaging, and biological markers of SVD in predicting the transition from MCI to dementia.8 To be included, patients had (1) MCI (Winblad criteria)9 and (2) moderate to severe degrees of white matter hyperintensities (WMH) on MRI, (modified Fazekas scale).10 The local ethics committee approved the study and informed consent was obtained from all participants.
At baseline, demographic variables (age, education, and sex) were collected, and both MoCA and MMSE were administered. For cut-off values and correction of age and education effect, we used norms validated in the Italian population.5,6 Conventional MRI features included lacunar infarcts, WMH, global cortical atrophy, and medial temporal lobe atrophy. Median values of mean diffusivity (MD) and fractional anisotropy of the cerebral white matter were used as DTI-derived indices (Figure). Other details of study methodology, clinical and MRI protocol are presented in the online-only Data Supplement.
Statistical analysis included adjusted partial correlation analysis between MoCA, MMSE, and DTI-derived indices (see online-only Data Supplement).
At baseline, 76 patients had both clinical and DTI assessment (Table 1; see online-only Data Supplement).
Univariate analyses showed a significant association of both MoCA and MMSE with age, education, cortical global atrophy, and medial temporal lobe atrophy, whereas no association emerged with WMH and lacunar infarcts. MD and fractional anisotropy only correlated with MoCA score (Table 2).
In partial correlation analysis between MoCA, MMSE, and DTI-derived indices, adjusted for demographics and conventional MRI variables, only MoCA proved significantly associated with MD (r=−0.275, P=0.023) and fractional anisotropy (r=0.246, P=0.043). No significant correlation was observed between MMSE- and DTI-derived indices (MD: r=−0.107, P=0.385; fractional anisotropy: r=0.219, P=0.073).
Concerning MoCA subtests, correlation analysis showed a significant association between MD and visuoexecutive (ρ=−0.372, P=0.001) and attentional (rbp=−0.259, P=0.026) tasks (Table in the online-only Data Supplement).
In our sample of patients with MCI and SVD, white matter microstructural damage, as evaluated by DTI-derived indices, was related to MoCA but not to MMSE performances, supporting the hypothesis that MoCA is more sensitive to the presence of subtle SVD.
One limitation of the study is that our cohort might not be purely vascular as imaging markers of neurodegeneration, are present. This reflects the frequent coexistence of vascular and degenerative mechanisms in the aging brain.
We found no statistically significant difference between patients with moderate and severe WMH in terms of MMSE or MoCA scores. This maybe due to a loss of accuracy in discriminating among patients subgroup using cognitive screening tests once a certain degree of SVD is reached. However, patients with severe WMH had on average a 2-point lower score on MoCA in comparison with those with moderate WMH.
Consistent with our hypothesis and results, other studies showed that DTI-derived indices correlated with executive dysfunction in patients with SVD,7 whereas conflicting results derive from previous studies comparing MoCA and MMSE in patients with SVD.11
Our data confirm the hypothesis that microstructural damage related to SVD is more expressed by MoCA than MMSE performances and that MoCA is a suited screening tool for patients with SVD. This is probably because of the psychometrical structure of MoCA, in particular the presence of items reflecting executive functions and psychomotor speed.
Vascular Mild Cognitive Impairment Tuscany (VMCI-Tuscany) study participants are reported in supplemental material.
Sources of Funding
Vascular Mild Cognitive Impairment Tuscany (VMCI-Tuscany) study is funded by Tuscany region. Dr Salvadori is currently supported by a project funded by Tuscany region and Health Ministry (Grant number: RF-2010-2321706, Principal Investigator: Dr Pantoni).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.114.007553/-/DC1.
- Received September 24, 2014.
- Revision received October 20, 2014.
- Accepted October 21, 2014.
- © 2014 American Heart Association, Inc.
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