Disease tracking markers for Alzheimer's disease at the prodromal (MCI) stage

Valeria Drago, Claudio Babiloni, David Bartrés-Faz, Anna Caroli, Beatriz Bosch, Tilman Hensch, Mira Didic, Hans Wolfgang Klafki, Michela Pievani, Jorge Jovicich, Luca Venturi, Philipp Spitzer, Fabrizio Vecchio, Peter Schoenknecht, Jans Wiltfang, Alberto Redolfi, Gianluigi Forloni, Olivier Blin, Elaine Irving, Ceri DavisHans Goran Hrdemark, Giovanni B. Frisoni

Research output: Contribution to journalArticlepeer-review


Older persons with Mild Cognitive Impairment (MCI) feature neurobiological Alzheimer's Disease (AD) in 50% to 70% of the cases and develop dementia within the next 5 to 7 years. Current evidence suggests that biochemical, neuroimaging, electrophysiological, and neuropsychological markers can track the disease over time since the MCI stage (also called prodromal AD). The amount of evidence supporting their validity is of variable strength. We have reviewed the current literature and categorized evidence of validity into three classes: Class A, availability of multiple serial studies; Class B a single serial study or multiple cross sectional studies of patients with increasing disease severity from MCI to probable AD; and class C, multiple cross sectional studies of patients in the dementia stage, not including the MCI stage. Several Class A studies suggest that episodic memory and semantic fluency are the most reliable neuropsychological markers of progression. Hippocampal atrophy, ventricular volume and whole brain atrophy are structural MRI markers with class A evidence. Resting-state fMRI and connectivity, and diffusion MR markers in the medial temporal white matter (parahippocampus and posterior cingulum) and hippocampus are promising but require further validation. Change in amyloid load in MCI patients warrant further investigations, e.g. over longer period of time, to assess its value as marker of disease progression. Several spectral markers of resting state EEG rhythms that might reflect neurodegenerative processes in the prodromal stage of AD (EEG power density, functional coupling, spectral coherence, and synchronization) suffer from lack of appropriately designed studies. Although serial studies on late event-related potentials (ERPs) in healthy elders or MCI patients are inconclusive, others tracking disease progression and effects of cholinesterase inhibiting drugs in AD, and cross-sectional including MCI or predicting development of AD offer preliminary evidence of validity as a marker of disease progression from the MCI stage. CSF Markers, such as Aβ 1-42, t-tau and p-tau are valuable markers which support the clinical diagnosis of Alzheimer's disease. However, these markers are not sensitive to disease progression and cannot be used to monitor the severity of Alzheimer's disease. For Isoprostane F2 some evidence exists that its increase correlates with the progression and the severity of AD.

Original languageEnglish
Pages (from-to)331-371
Number of pages41
JournalAdvances in Alzheimer's Disease
Publication statusPublished - 2011


  • Alzheimer's disease
  • cerebrospinal fluid
  • diffusion tensor imaging
  • EEG
  • functional MRI
  • Mild cognitive impairment
  • neuroimaging
  • neuropsychology
  • positron emission tomography
  • spectroscopy

ASJC Scopus subject areas

  • Clinical Neurology

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