Drug discovery efforts in Alzheimer’s disease (AD) have been directed in the last ten years to develop
“disease-modifying drugs” able to exert neuroprotective effects in an early phase of AD pathogenesis. Unfortunately
several candidate disease-modifying drugs have failed in Phase III clinical trials conducted in mild to moderate AD for
different methodological difficulties, such as the time course of treatment in relation to development of disease as well as
the appropriate use of validated biological and neuropsychological markers. Mild cognitive impairment (MCI) has been
considered a precursor of AD. Much effort is now directed to identify the most appropriate and sensitive markers which
can predict the progression from MCI to AD, such as neuroimaging markers (e.g. hippocampal atrophy and amyloid
positron emission tomography imaging), cerebrospinal fluid markers (i.e. association of elevated tau with low levels of
amyloid β -peptide(1-42) and neuropsychological markers (i.e. episodic memory deficits and executive dysfunction).
Recent studies demonstrate that the combination of these different biomarkers significantly increases the chance to predict
the conversion into AD within 24 months. These biomarkers will be essential in the future to analyze clinical efficacy of
disease-modifying drugs in MCI patients at high risk to develop AD. In the present review we analyze recent evidence on
the combination of neuropsychological and biological markers in AD as a new tool to track disease progression in early
AD as well as the response to disease-modifying drugs.
Keywords: Alzheimer’s disease, biological markers, disease-modifying drugs, mild cognitive impairment, neuropsychological
tests, risk factors.
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