%0 Journal Article %J J Alzheimers Dis %D 2017 %T Cerebrospinal Fluid Amyloid-β 42, Total Tau and Phosphorylated Tau are Low in Patients with Normal Pressure Hydrocephalus: Analogies and Differences with Alzheimer's Disease. %A Santangelo, Roberto %A Cecchetti, Giordano %A Bernasconi, Maria Paola %A Cardamone, Rosalinda %A Barbieri, Alessandra %A Pinto, Patrizia %A Passerini, Gabriella %A Scomazzoni, Francesco %A Comi, Giancarlo %A Magnani, Giuseppe %X

Co-existence of Alzheimer's disease (AD) in normal pressure hydrocephalus (NPH) is a frequent finding, thus a common pathophysiological basis between AD and NPH has been postulated. We measured CSF amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) concentrations in a sample of 294 patients with different types of dementia and 32 subjects without dementia. We then compared scores on neuropsychological tests of NPH patients with pathological and normal CSF Aβ42 values. Aβ42 levels were significantly lower in NPH than in control patients, with no significant differences between AD and NPH. On the contrary, t-tau and p-tau levels were significantly lower in NPH than in AD, with no differences between NPH and controls. NPH patients with pathological Aβ42 levels did not perform worse than NPH patients with normal Aβ42 levels in any cognitive domains. Our data seem to support the hypothesis of amyloid accumulation in brains of NPH patients. Nevertheless, amyloid does not seem to play a pathogenetic role in the development of cognitive deficits in NPH.

%B J Alzheimers Dis %V 60 %P 183-200 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/28826180?dopt=Abstract %R 10.3233/JAD-170186 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Optical Coherence Tomography Reveals Retinal Neuroaxonal Thinning in Frontotemporal Dementia as in Alzheimer's Disease. %A Ferrari, Laura %A Huang, Su-Chun %A Magnani, Giuseppe %A Ambrosi, Alessandro %A Comi, Giancarlo %A Leocani, Letizia %X

BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are leading causes of cognitive decline. Optical coherence tomography (OCT) allows the measurement of thickness of retinal neuroaxonal layers. While in AD and mild cognitive impairment (MCI), retinal nerve fiber layer (RNFL) thinning is frequently reported, less information is available on ganglion cell layer-inner plexiform layer (GCL-IPL). Data on FTD are lacking.

OBJECTIVE: To obtain cross-sectional information on RNFL and GCL-IPL thickness among MCI, AD, FTD, and healthy controls (HC), and their correlations with dementia severity.

METHODS: Peripapillary OCT scans were obtained in 27 MCI, 39 AD, 17 FTD, 49 HC using high-definition Heidelberg Spectral-domain OCT, with RNFL and GCL-IPL thickness measurement. Statistical analysis tested group effects and correlation with gender, disease duration and severity (Mini-Mental State Examination, MMSE).

RESULTS: RNFL showed a significant group effect [F(4,132) = 3.786, p = 0.006], being reduced versus controls in MCI (p = 0.033), moderate AD (p = 0.025), and FTD (p < 0.001), and versus mild AD in FTD (p = 0.042). GCL-IPL showed a significant group effect as well [F(4,121) = 5.104, p < 0.001], with reduction in moderate AD versus HC (p < 0.001), MCI (p = 0.037), and mild AD (p = 0.009); in FTD versus HC (p = 0.002) and mild AD (p = 0.038). In AD, GCL-IPL correlated with MMSE (r = 0.487, p = 0.003), without significant effects of age, gender, or disease duration.

CONCLUSION: Retinal neuroaxonal thinning occurs in MCI/AD consistently with previous reports, as well as in FTD. Correlation with disease severity in AD suggests that retinal and brain neurodegeneration may occur in parallel to some extent, and prompts larger studies aimed at providing surrogate endpoints for clinical trials in AD.

%B J Alzheimers Dis %V 56 %P 1101-1107 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28106555?dopt=Abstract %R 10.3233/JAD-160886 %0 Journal Article %J J Alzheimers Dis %D 2016 %T CHRNA7 Gene and Response to Cholinesterase Inhibitors in an Italian Cohort of Alzheimer's Disease Patients. %A Clarelli, Ferdinando %A Mascia, Elisabetta %A Santangelo, Roberto %A Mazzeo, Salvatore %A Giacalone, Giacomo %A Galimberti, Daniela %A Fusco, Federica %A Zuffi, Marta %A Fenoglio, Chiara %A Franceschi, Massimo %A Scarpini, Elio %A Forloni, Gianluigi %A Magnani, Giuseppe %A Comi, Giancarlo %A Albani, Diego %A Martinelli Boneschi, Filippo %X

Previous studies suggest that genetic variants in CHRNA7, which encodes for the major subunit of the acetylcholine receptor (α7-nAChR), are associated with the clinical response to cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) patients. We sought to replicate the association of two SNPs in the CHRNA7 gene, rs6494223 and rs8024987, with response to ChEI treatment in an Italian cohort of 169 AD patients, further extending the study to gene-level analysis. None of the tested variants was associated with clinical response. However, rs6494223 showed a consistent effect direction (OR = 1.4; p = 0.17), which after meta-analysis with previous study yielded a significant result (OR = 1.57, p = 0.02, I2 = 0%).

%B J Alzheimers Dis %V 52 %P 1203-8 %8 2016 Apr 16 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27104904?dopt=Abstract %R 10.3233/JAD-160074 %0 Journal Article %J J Alzheimers Dis %D 2016 %T 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. %A Mazzeo, Salvatore %A Santangelo, Roberto %A Bernasconi, Maria Paola %A Cecchetti, Giordano %A Fiorino, Agnese %A Pinto, Patrizia %A Passerini, Gabriella %A Falautano, Monica %A Comi, Giancarlo %A Magnani, Giuseppe %X

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.

%B J Alzheimers Dis %V 54 %P 1495-1508 %8 2016 Oct 18 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27589522?dopt=Abstract %R 10.3233/JAD-160360