Patients with hypertension who show substantial progression of cerebral small vessel disease over time have sixfold higher odds of developing mild cognitive impairment than do those without signs of progression on brain MRI, new research has found.
American Heart Association
The results, published online Jan. 4 in Hypertension, come from a longitudinal, population-based study of 976 patients with hypertension but with no history of dementia or clinical stroke. Participants underwent a vascular risk assessment, brain MRI, cognitive evaluation, and blood sampling at baseline, and 345 patients were also retested after a mean of nearly 4 years.
Researchers saw significant sixfold higher odds of developing incident mild cognitive impairment (MCI) among individuals who showed marked progression of periventricular white matter hyperintensities – an imaging hallmark of cerebral small vessel disease – compared with individuals who did not show any progression (odds ratio = 6.184; 95% confidence interval, 1.506-25.370; P = .011).
Patients with greater progression of periventricular white matter hyperintensities also showed significantly greater decreases in global cognition scores – both in total DRS-2 Z-score and executive function Z-score – when compared against individuals without white matter hyperintensity progression.
“As MCI is one of the most important risk factors in the development of dementia, future research should investigate the mechanisms by which PVH [periventricular white matter hyperintensities] trigger cognitive impairment and the clinical utility of its assessment,” wrote Joan Jiménez-Balado of Vall d’Hebron Research Institute, Barcelona, and his associates.
However, deep white matter hyperintensity progression – as opposed to periventricular – was not linked to cognitive changes, except in the case of bilateral occipital deep white matter hyperintensity changes, which were linked to a significant worsening in the attention Z-score.
The authors noted that the different impacts of periventricular versus deep white matter hyperintensities may relate to a number of factors. The first was that deep white matter hyperintensities disrupt cortico-cortical connections but periventricular ones are more likely to affect long cortico-subcortical association fibers, which “would be an important variable to determine the impaired networks involved in cognition.”
They also suggested that periventricular and deep white matter hyperintensities may affect different neuromodulator systems; the periventricular white matter could be closer to ascending cholinergic bundles that may play a role in vascular cognitive impairment.
Periventricular white matter hyperintensities may also accelerate the deposition of amyloid because of their association with venous collagenosis, which is linked to ischemia and disruptions of the interstitial fluid circulation.
“On the other hand, [deep white matter hyperintensity] may be more related to hypoperfusion, as deep areas are particularly vulnerable to low [blood pressure],” the authors wrote, while stressing that the pathophysiology of white matter hyperintensities is not fully understood, so further research is needed.
Overall, the 345 patients with follow-up data had a median age of 65 years at baseline and mean blood pressure of 143/78.2 mm Hg at baseline and 146.5/75 mm Hg at follow-up. White matter hyperintensity changes occurred periventricularly in 22% and in deep white matter in 48%. The researchers saw new infarcts in 6.1% of patients, and 5.5% had incident cerebral microbleeds. While incident cerebral microbleeds were significantly associated with declines in the attention Z-score, they did not affect other cognitive functions, and incidental infarcts were also not associated with cognitive changes.
Baseline blood pressure and average blood pressure during follow-up were not associated with changes in cardiac small vessel disease lesions. However, diastolic – but not systolic – blood pressure at baseline and follow-up was positively correlated with total, attention, and executive function DRS-2 Z-scores at follow-up.
Three-quarters of patients showed cognitive changes associated with normal aging both at baseline and follow-up, 9.1% had stable MCI, and 9.1% of patients had incident MCI. However, 6.6% of subjects reverted back to normal aging after having MCI at baseline.
The authors noted that they did not examine markers of neurodegeneration, such as tau or amyloid-beta, which could also be linked to hypertension and cerebral small vessel disease lesions.
The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.
SOURCE: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090