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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.
J Alzheimers Dis 2016; 54(4):1495-1508JA

Abstract

BACKGROUND

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.

OBJECTIVE

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.

METHODS

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.

RESULTS

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%.

DISCUSSION

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+Show Affiliations

Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy.Laboraf, IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27589522

Citation

Mazzeo, Salvatore, et al. "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." Journal of Alzheimer's Disease : JAD, vol. 54, no. 4, 2016, pp. 1495-1508.
Mazzeo S, Santangelo R, Bernasconi MP, et al. 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. J Alzheimers Dis. 2016;54(4):1495-1508.
Mazzeo, S., Santangelo, R., Bernasconi, M. P., Cecchetti, G., Fiorino, A., Pinto, P., ... Magnani, G. (2016). 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. Journal of Alzheimer's Disease : JAD, 54(4), pp. 1495-1508.
Mazzeo S, et al. 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. J Alzheimers Dis. 2016 10 18;54(4):1495-1508. PubMed PMID: 27589522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Mazzeo,Salvatore, AU - Santangelo,Roberto, AU - Bernasconi,Maria Paola, AU - Cecchetti,Giordano, AU - Fiorino,Agnese, AU - Pinto,Patrizia, AU - Passerini,Gabriella, AU - Falautano,Monica, AU - Comi,Giancarlo, AU - Magnani,Giuseppe, PY - 2016/10/22/pubmed PY - 2018/1/25/medline PY - 2016/9/3/entrez KW - Amyloid-β42 KW - composite cognitive score KW - diagnostic algorithm KW - mild cognitive impairment KW - neuropsychological tests KW - tau protein SP - 1495 EP - 1508 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 54 IS - 4 N2 - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. DISCUSSION: 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/27589522/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_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-160360 DB - PRIME DP - Unbound Medicine ER -