Data over the past several years have pointed toward the hypothesis that hypertension is a prevailing risk factor for the development of dementia. While conventional neuroimaging techniques have provided some insight into the development of neurodegeneration, it is becoming clear that by the time brain damage is visible, it may be too late for therapeutic intervention.
“The problem is that neurological alterations related to hypertension are usually diagnosed only when the cognitive deficit becomes evident, or when traditional magnetic resonance shows clear signs of brain damage,” explained co-senior study investigator Giuseppe Lembo M.D., Ph.D., professor in the department of molecular medicine at the Sapienza University of Rome. “In both cases, it is often too late to stop the pathological process.”
However now, investigators have just shown that an MRI can be used to detect very early signatures of neurological damage in people with high blood pressure before any symptoms of dementia occur. Findings from the new study were released today in Cardiovascular Research, in an article entitled “Brain MRI Fiber-Tracking Reveals White Matter Alterations in Hypertensive Patients without Damage at Conventional Neuroimaging.”
High blood pressure is a chronic condition that causes progressive organ damage. It is well known that the clear majority of cases of Alzheimer's disease and related dementia are not due to genetic predisposition but rather to chronic exposure to vascular risk factors. The clinical approach to the treatment of dementia patients usually starts only after symptoms are clear. However, it was becoming increasingly clear that when signs of brain damage are manifest, it may be too late to reverse the neurodegenerative process. Physicians still lack procedures for assessing progression markers that could reveal presymptomatic alterations and identify patients at risk of developing dementia.
To gain insights into the neurocognitive profile of patients, specific tests were administered. Researchers recruited people aged 40 to 65, compliant to give written informed consent and with the possibility to perform a dedicated 3 Tesla MRI scan. As a primary outcome of the study, the researchers aimed at finding any specific signature of brain changes in the white matter microstructure of hypertensive patients, associated with an impairment of the related cognitive functions.
“This work was conducted on hypertensive and normotensive subjects with no sign of structural damage at conventional neuroimaging and no diagnosis of dementia revealed by neuropsychological assessment,” the authors wrote. “All individuals underwent cardiological clinical examination in order to define the hypertensive status and the related target organ damage. Additionally, patients were subjected to DTI-MRI scan to identify microstructural damage of WM [white matter] by probabilistic fiber-tracking. To gain insights into the neurocognitive profile of patients a specific battery of tests was administered.”
The result indicated that hypertensive patients showed significant alterations in three specific white matter fiber-tracts. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those fiber-tracts, showing decreased performances in executive functions, processing speed, memory, and related learning tasks.
“As a primary outcome of the study we aimed at finding any specific signature of fiber-tracts alterations in hypertensive patients, associated with an impairment of the related cognitive functions,” the authors penned. “Hypertensive patients showed significant alterations in three specific WM fiber-tracts: the anterior thalamic radiation, the superior longitudinal fasciculus, and the forceps minor. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those WM fiber-tracts, showing decreased performances in executive functions, processing speed, memory, and paired associative learning tasks.”
Overall, white matter fiber-tracking on MRIs showed an early signature of damage in hypertensive patients when otherwise undetectable by conventional neuroimaging. As these changes can be detected before patients show symptoms, these patients could be targeted with medication earlier to prevent further deterioration in brain function. These findings are also widely applicable to other forms of the neurovascular disease, where early intervention could be of marked therapeutic benefit.
“We have been able to see that, in the hypertensive subjects, there was a deterioration of white matter fibers connecting brain areas typically involved in attention, emotions, and memory,” concludes lead study investigator Lorenzo Carnevale, Ph.D., an IT engineer at the Institute for Research and Health Care. “An important aspect to consider is that all the patients studied did not show clinical signs of dementia and, in conventional neuroimaging, they showed no signs of cerebral damage. Of course, further studies will be necessary, but we think that the use of tractography will lead to the early identification of people at risk of dementia, allowing timely therapeutic interventions.”