Biomarkers of Dementia

Dementia is defined as “a global impairment of higher cortical functions, including memory, the capacity to solve the problems of everyday living, the performance of learned perceptual motor skills and the correct use of social skills and the control of emotional reactions, in the absence of gross clouding of consciousness” (Royal College of Physicians 1981). There are numerous causes of primary dementia include degenerative diseases such as Alzheimer diseases (AD) and chronic cerebrovascular insufficieny such as vascular dementia. There mixed vascular and degenerative dementas as well. Secondary dementias may occur due to other disorders such as metabolic encephalopathies, nutritional deficiencies, neurotoxicity, CNS infections, brain tumors, and normal pressure hydrocephalus. The diagnosis can be established by biomarkers of the primary disease. Biomarkers of neurodegenerative disorders will be described in the following sections.

Biomarkers of Vascular Dementia

There is no general agreement as to its definition of vascular dementia (VD). The term “vascular” may be obsolete and “dementia” implies that a patient has reached a state from which recovery is unlikely but cognitive impairment due to disturbances of blood circulation may be reversible. Alternative term of vascular cognitive impairment has been used. Another term that has been used in the literature in the past is multi-infarct dementia but VD has a broader connotation and is the most widely used term to describe cognitive impairment after stroke. Post-stroke dementia is another term used to describe this condition. The only catch to this is that a patient with vascular disease may develop dementia without any manifest stroke but rather silent strokes. VD is characterized by abnormalities of white matter, which are clearly detectable with CT or MRI. The association of dementia, hypertension, extensive white matter lesions and small subcortical infarcts is characteristic. Subcortical vascular cognitive impairment is now recognized to be the commonest form of vascular cognitive impairment, its clinical pattern, risk factors, and imaging features being sufficiently consistent for it to be considered an entity for the purposes of diagnosis, clinical trials, and management. It is recognized as subcortical vascular dementia in the International Classification of Diseases. Both stroke and AD are common disorders of aging and are commonly associated. It is often difficult to prove whether stroke directly causes VD, contributes to its development or is merely coincidental. Pathologically subcortical VD may be difficult to distinguish from AD in elderly subjects because mixed forms of both dementias exist quite frequently in the same subject.

Cerebral endothelial dysfunction occurs in several neurodegenerative diseases. A population-based prospective study has shown that elevated plasma concentration of midregional pro-adrenomedullin (MR-proADM) is an independent predictor of vascular dementia, and an increase in C-terminal endothelin-1 (CT-proET-1) indicates higher risk of VD as well as other dementia subtypes (Holm et al. 2017).

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