Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. METHODS: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. RESULTS: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. CONCLUSIONS: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

The novel I213S mutation in PSEN1 gene is located in a hotspot codon associated with familial early-onset Alzheimer's disease.

Mutations in presenilin 1 gene (PSEN1) are the most common causes of autosomal dominant early-onset Alzheimer's disease (EOAD). We report a novel PSEN1 mutation (I213S) that was discovered in an Italian patient with a family history of early-onset dementia, who developed a slowly progressive cognitive decline since the age of 40 years. Clinical investigations, including neuropsychological assessment, brain MRI and 18-fluorodeoxyglucose PET, as well as cerebrospinal fluid biomarkers, supported the diagnosis of EOAD. Genetic studies identified a novel missense mutation at codon 213 (I213S). Three other mutations at the same codon have been described in association with EOAD. Previous in silico, in vitro and in vivo studies indicated that these mutations affect the functional properties of γ-secretase and are most likely pathogenic. In silico algorithms suggested that even the I213S mutation has similar deleterious effects on PSEN1 structure and function. Overall, these data strongly support a role of hotspot site for the codon 213 of PSEN1, and provide evidence that the genetic variants located on this site cause EOAD.