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Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ42 levels, comparable with Alzheimer’s Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ42, Aβ42/Aβ40, p-tau, t-tau) in iNPH. To this purpose, we enrolled 44 patients diagnosed with iNPH and 101 with AD. All the patients underwent CSF sampling. We compared CSF biomarker levels in iNPH and AD: Aβ42 levels were not different between iNPH and AD, while Aβ42/Aβ40, p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ42/Aβ40 was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ42/Aβ40 had higher p-tau and t-tau than iNPH patients with negative Aβ42/Aβ40. Those iNPH patients who showed cognitive impairment had lower Aβ42/Aβ40 and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ42 with negative Aβ42/Aβ40, p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ42/Aβ40 in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology.

Background: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer&rsquo, s disease (AD) and Frontotemporal Dementia (FTD), to compare concordance between biomarkers, and to provide an indication of their use and interpretation. Methods: We included 148 patients (95 AD and 53 FTD), who underwent clinical evaluation, neuropsychological assessment, and at least one amyloid biomarker (CSF analysis or amyloid-PET). Thirty-six patients underwent both analyses. One-hundred-thirteen patients underwent Apolipoprotein E (ApoE) genotyping. Results: Amyloid-PET presented higher diagnostic accuracy, sensitivity, and NPV than CSF A&beta, 1&ndash, 42 but not A&beta, 42/40 ratio. Concordance between CSF biomarkers and amyloid-PET was higher in FTD patients compared to AD cases. None of the AD patients presented both negative A&beta, biomarkers. Conclusions: CSF A&beta, 42/40 ratio significantly increased the diagnostic accuracy of CSF biomarkers. On the basis of our current and previous data, we suggest a flowchart to guide the use of biomarkers according to clinical suspicion: due to the high PPV of both amyloid-PET and CSF analysis including A&beta, 42/40, in cases of concordance between at least one biomarker and clinical diagnosis, performance of the other analysis could be avoided. A combination of both biomarkers should be performed to better characterize unclear cases. If the two amyloid biomarkers are both negative, an underlying AD pathology can most probably be excluded.

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer’s disease. We aimed to evaluate the interaction between ApoE ε4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Methods: We included 68 patients who underwent clinical evaluation; neuropsychological assessment; ApoE, Clock and Per2 genotyping at baseline; and neuropsychological follow-up every 12–24 months for a mean of 13 years. We considered subjects who developed AD and non-converters. Results: Clock T3111C was detected in 47% of cases, Per2 C111G in 19% of cases. ApoE ε4 carriers presented higher risk of heart disease; Clock C-carriers were more frequently smokers than non C-carriers. During the follow-up, 17 patients progressed to AD. Age at baseline, ApoE ε 4 and dyslipidemia increased the risk of conversion to AD. ApoE ε4 carriers with history of dyslipidemia showed higher risk to convert to AD compared to ApoE ε4− groups and ApoE ε4+ without dyslipidemia patients. Clock C-carriers with history of blood hypertension had a higher risk of conversion to AD. Conclusions: ApoE and Clock T3111C seem to interact with cardiovascular risk factors in SCD and MCI patients influencing the progression to AD.

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer&rsquo, s disease. We aimed to evaluate the interaction between ApoE &epsilon, 4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Methods: We included 68 patients who underwent clinical evaluation, neuropsychological assessment, ApoE, Clock and Per2 genotyping at baseline, and neuropsychological follow-up every 12&ndash, 24 months for a mean of 13 years. We considered subjects who developed AD and non-converters. Results: Clock T3111C was detected in 47% of cases, Per2 C111G in 19% of cases. ApoE &epsilon, 4 carriers presented higher risk of heart disease, Clock C-carriers were more frequently smokers than non C-carriers. During the follow-up, 17 patients progressed to AD. Age at baseline, ApoE &epsilon, 4 and dyslipidemia increased the risk of conversion to AD. ApoE &epsilon, 4 carriers with history of dyslipidemia showed higher risk to convert to AD compared to ApoE &epsilon, 4&minus, groups and ApoE &epsilon, 4+ without dyslipidemia patients. Clock C-carriers with history of blood hypertension had a higher risk of conversion to AD. Conclusions: ApoE and Clock T3111C seem to interact with cardiovascular risk factors in SCD and MCI patients influencing the progression to AD.