title: Disease tracking markers for Alzheimer's disease at the prodromal (MCI) stage.
abstract: 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.
authors.affiliation: LENITEM Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS San Giovanni di Dio - Fatebenefratelli, Brescia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Drago
authors.forename: Claudio
authors.initials: C
authors.lastname: Babiloni
authors.forename: David
authors.initials: D
authors.lastname: Bartrés-Faz
authors.forename: Anna
authors.initials: A
authors.lastname: Caroli
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bosch
authors.forename: Tilman
authors.initials: T
authors.lastname: Hensch
authors.forename: Mira
authors.initials: M
authors.lastname: Didic
authors.forename: Hans-Wolfgang
authors.initials: HW
authors.lastname: Klafki
authors.forename: Michela
authors.initials: M
authors.lastname: Pievani
authors.forename: Jorge
authors.initials: J
authors.lastname: Jovicich
authors.forename: Luca
authors.initials: L
authors.lastname: Venturi
authors.forename: Philipp
authors.initials: P
authors.lastname: Spitzer
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vecchio
authors.forename: Peter
authors.initials: P
authors.lastname: Schoenknecht
authors.forename: Jans
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Alberto
authors.initials: A
authors.lastname: Redolfi
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Olivier
authors.initials: O
authors.lastname: Blin
authors.forename: Elaine
authors.initials: E
authors.lastname: Irving
authors.forename: Ceri
authors.initials: C
authors.lastname: Davis
authors.forename: Hans-goran
authors.initials: HG
authors.lastname: Hårdemark
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000503:physiopathology; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D006801:Humans; D059906:Neuroimaging / Q000379:methods; D009483:Neuropsychological Tests; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers