Brain Microbleeds in Patients Linked to Cognitive Decline, MRI Study Shows

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

Share this article:

Share article via email
Microbleeds, MRI scans

Microbleeds found in the brains of people with Parkinson’s disease by magnetic resonance imaging (MRI) scans were associated with cognitive decline, a study demonstrated. 

Higher levels of a microbleed-associated biomarker also were found in patients with dementia.

Moreover, a statistical analysis found the presence of certain microbleeds was independently associated with a fivefold higher risk of Parkinson’s dementia.

These findings suggest that, along with blood biomarkers, microbleeds may serve as a radiological marker for cognitive decline in this patient population, the scientists said. 

The study, “Amyloid related cerebral microbleed and plasma Aβ40 are associated with cognitive decline in Parkinson’s disease,” was published in the journal Nature Scientific Reports

People with Parkinson’s disease are known to be at a higher risk of developing cognitive impairment and dementia. Several mechanisms have been proposed for cognitive decline, including Lewy body formation, which are clumps of proteins found in damaged brain cells. 

A co-existing disease of small blood vessels in the brain — called small vessel disease (SVD) — also may be a contributing factor for dementia, according to researchers, who note that brain imaging studies have associated SVD with cognitive impairment in people with Parkinson’s.

Cerebral microbleeds (MBs), or tiny hemorrhages in the brain’s outer layer, called the cerebral cortex, are a characteristic feature of SVD. These microbleeds are risk factors for cognitive impairment in aging people. However, their role in Parkinson’s disease development and progression remains unclear.

To learn more, researchers at the National Taiwan University Hospital, in Taipai, used blood-sensitive MRI scans to examine whether microbleeds are associated with risk and severity — especially cognitive decline — in people with Parkinson’s. The team measured the levels of protein biomarkers for brain microbleeds in the blood of Parkinson’s patients and healthy people (controls).

A total of 135 people with the disease, with a mean age of 67.6, were included in the study, along with 34 neurologically normal controls, also with a mean age of 67.6. 

Results revealed the prevalence of microbleeds in the lobes of the cortex (lobar) was significantly higher in people with Parkinson’s than controls (20.7% vs. 2.9%). More microbleeds in deeper regions of the brain (deep MBs) were found (8.1% vs. 5.9%) as well as in the brainstem and cerebellum region at the base of the brain (7.4% vs. 2.9%), but these differences did not reach statistical significance.

A comparison of Parkinson’s patients with different motor and cognitive abilities showed the prevalence of lobar and deep microbleeds was similar between those in the early stages of the disease and patients with advanced-stage motor symptoms.

A total of 39 Parkinson’s participants (28.9%)  were diagnosed with dementia. Compared with patients without dementia, those with dementia were older (72.0 vs. 65.8 years) and had worse motor function assessed by the Unified Parkinson Disease Rating Scale (UPDRS) Part III.

A brain scan analysis found that patients with dementia had a higher prevalence of lobar microbleeds than those without dementia (33.3% vs. 15.6%). Additionally, these participants had more severe white matter hyperintensities (WMHs), which are lesions in the brain that appear as areas of increased brightness. They also had reduced volume of the hippocampus, and a thinner cortex over the frontal, temporal, and parietal lobes. 

A statistical analysis found the presence of lobar microbleeds was independently associated with a fivefold higher risk of Parkinson’s dementia after adjusting for age, sex, vascular risk factors including high blood pressure and diabetes, disease stage, and medication use.

This finding suggests that “microvascular pathology in the cortical vessels may contribute to the cognitive dysfunction in [Parkinson’s] patients,” the researchers wrote. 

Patients with dementia, compared with those without, had higher levels of a blood biomarker associated with microbleeds, called amyloid beta-40 (129.23 vs. 95.37 picograms per mL). Levels of another microbleed marker, amyloid beta-42, were similar between the two groups. Additionally, the ratio of amyloid beta-42 to amyloid beta-40 was lower in dementia patients than in those with normal cognition.

Total levels of two proteins associated with Lewy bodies, alpha-synuclein and tau protein, also were higher in the blood of cognitively impaired Parkinson’s patients. After adjusting for age and sex, the association between Parkinson’s dementia and tau levels, amyloid beta-40, and the amyloid beta-42 to amyloid beta-40 ratio remained. 

Finally, MMSE scores — a measure of cognitive impairment — were independently associated with tau, amyloid beta-40, and the amyloid beta-42 to amyloid beta-40 ratio after adjusting for age and sex. Also, amyloid beta-40 was independently associated with the volume of the hippocampus.  

“Further functional studies in animal models or post-mortem brain pathology studies are needed to unravel the role of [amyloid beta-40] in the pathophysiology of [Parkinson’s dementia], the team added.

The researchers noted that Parkinson’s patients have a three- to six-times higher risk of developing dementia in comparison with age-matched people without the neurodegenerative disease.

“In summary, our findings revealed a higher prevalence of lobar MBs in [Parkinson’s disease] patients compared to healthy controls,” the researchers wrote. “The presence of lobar MBs is an independent predictor of [Parkinson’s dementia] and may help clinicians identify patients at risk of cognitive decline in clinical practice.”

“The association between elevated plasma levels of [amyloid beta-40] and cognitive impairment in [Parkinson’s disease] further supports amyloid-related microvascular injury as a potential contributor to the pathophysiology of [Parkinson’s dementia],” they added.