title: Combining Cerebrospinal Fluid Biomarkers and Neuropsychological Assessment: A Simple and Cost-Effective Algorithm to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease Dementia.
abstract: Correctly diagnosing Alzheimer's disease (AD) in prodromal phases would allow the adoption of experimental therapeutic strategies that could selectively interrupt the pathogenetic process before neuronal damage becomes irreversible. Therefore, great efforts have been aimed at finding early reliable disease markers.
  
  
  
  The aim of this study was to identify a simple, cost effective, and reliable diagnostic algorithm to predict conversion from mild cognitive impairment (MCI) to AD.
  
  
  
  96 consecutive MCI patients admitted to the Neurology department of San Raffaele Hospital in Milan between January 2009 and January 2015 were included. All patients underwent neuropsychological assessment and lumbar puncture with CSF analysis of amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) levels. Each patient underwent clinical and neuropsychological follow-up, in order to identify a possible progression from MCI to AD. The mean follow up time was 36.73 months.
  
  
  
  37 out of 96 MCI converted to AD during follow up. CSF analysis and neuropsychological assessment reliably detected MCI patients who developed AD. In a subsample of 43 subjects, a Composite Cognitive Score (CCS) was calculated including episodic memory, executive function, and verbal fluency tests. Combining together CSF biomarkers and CCS increased the accuracy of the single predictors, correctly classifying 86% of patients with a specificity of 96% and a Positive Predictive Value of 93%.
  
  
  
  Even if preliminary, our data seem to suggest that CSF analysis and neuropsychological assessment could detect MCI patients who will convert to AD with high confidence. Their relative low cost and availability could make them worldwide essential tools in future clinical trials.
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Salvatore
authors: S
authors: Mazzeo
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Roberto
authors: R
authors: Santangelo
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Maria Paola
authors: MP
authors: Bernasconi
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Giordano
authors: G
authors: Cecchetti
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Agnese
authors: A
authors: Fiorino
authors: Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors: Patrizia
authors: P
authors: Pinto
authors: Laboraf, IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Gabriella
authors: G
authors: Passerini
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Monica
authors: M
authors: Falautano
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Giancarlo
authors: G
authors: Comi
authors: Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
authors: Giuseppe
authors: G
authors: Magnani
mesh_terms: D000368:Aged; D000465:Algorithms; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000191:economics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000191:economics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000191:economics; D003362:Cost-Benefit Analysis / Q000379:methods*; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000191:economics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000191:economics; D011237:Predictive Value of Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000191:economics
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Amyloid-β42; composite cognitive score; diagnostic algorithm; mild cognitive impairment; neuropsychological tests; tau protein