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Content archived on 2024-05-30

Combining sensitive biomarkers for early diagnosis of AD: A multi-modal approach

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Novel biomarkers for dementia

The pathological mechanisms of neurodegeneration manifest long before disease symptoms. Diagnosis of this stage requires the identification of novel biomarkers.

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Alzheimer's disease is a primary cause of dementia worldwide with a rising incidence due to an increase of the ageing population. Neurons in these patients die well before the pathological mechanisms of dementia manifest. During this stage, known as mild cognitive impairment, effective treatments would have the greatest impact. However, existing neuroimaging, cerebrospinal fluid and neuropsychological biomarkers do not hold sufficient diagnostic or prognostic value. To address this, scientists of the EU-funded AD BIOMARKERS (Combining sensitive biomarkers for early diagnosis of AD: A multi-modal approach) project set out to identify neuroimaging biomarkers for the diagnosis of mild cognitive impairment due to Alzheimer's disease and Parkinson's disease. They worked to detect patterns of brain abnormalities that could explain the development of cognitive dysfunction. To this end, they employed structural magnetic resonance imaging (MRI), diffusion tensor imaging and resting-state functional MRI. Structural MRI helped scientists detect medial temporal atrophy, a feature that was associated with dementia in nearly 80 % of the cases one year later. Additional demographic, clinical and genetic variables such as the apolipoprotein e4 allele also affected the onset of medial temporal atrophy. With respect to Parkinson's disease, researchers observed that compared to healthy controls, patients with mild cognitive impairment presented with widespread cortical thinning. These structural abnormalities were strongly linked with cognitive deficits, indicating that mild cognitive impairment in Parkinson's disease increased patient vulnerability towards dementia. The brain networks in these patients were also weaker and suffered from inefficient communication. Regarding cerebrospinal fluid biomarkers, Abeta-42 levels were significantly decreased in patients with mild cognitive impairment while lower α-synuclein levels were associated with attention and cognitive performance. Taken together, the findings of the AD BIOMARKERS clearly indicated that some of the hallmarks of Alzheimer's disease (medial temporal atrophy and amyloid pathology) can also be found in Parkinson's patients. This suggests that different neurodegenerative disorders might share common disease propagation mechanisms and similar neuroimaging diagnostic techniques could help identifying patients with a higher risk of developing dementia.

Keywords

Biomarkers, dementia, Alzheimer’s disease, Parkinson’s disease, MRI, apolipoprotein, α-synuclein

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