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Background: The Free and Cued Selective Reminding Test (FCSRT), assessing verbal episodic memory with controlled learning and semantic cueing, has been recommended for detecting the genuine encoding and storage deficits characterizing AD-related memory disorders., Objective: The present study aims at investigating the ability of FCSRT in predicting cerebrospinal fluid (CSF) evidence of amyloid-β positivity in subjects with amnestic mild cognitive impairment (aMCI) and exploring its associations with amyloidopathy, tauopathy and neurodegeneration biomarkers., Methods: 120 aMCI subjects underwent comprehensive neurological and neuropsychological examinations, including the FCSRT assessment, and CSF collection; CSF Aβ42/40 ratio, p-tau181, and total-tau quantification were conducted by an automated CLEIA method on Lumipulse G1200. Based on the Aβ42/40 ratio value, subjects were classified as either A+ or A-., Results: All FCSRT subitem scores were significantly lower in A+ group and significantly predicted the amyloid-β status, with Immediate Total Recall (ITR) being the best predictor. No significant correlations were found between FCSRT and CSF biomarkers in the A- aMCI group, while in the A+ aMCI group, all FCSRT subitem scores were negatively correlated with CSF p-tau181 and total-tau, but not with the Aβ42/40 ratio., Conclusions: FCSRT confirms its validity as a tool for the diagnosis of AD, being able to predict the presence of amyloid-β deposition with high specificity. The associations between FCSRT subitem scores and CSF p-tau-181 and total-tau levels in aMCI due to AD could further encourage the clinical use of this simple and cost-effective test in the evaluation of individuals with aMCI.

Semantic and, to a lesser extent, phonological verbal fluency tasks are impaired in Alzheimer's disease (AD) and in amnesic mild cognitive impairment (aMCI). Furthermore, both fluency tasks have been considered as possible markers of conversion from aMCI to AD. Up to recent years, the use of fluency tasks has been limited to word count, but, more recently, linguistic variables, such as word frequency, age of acquisition, familiarity, and typicality, have also been considered. In particular, attention has been focused on typicality of words produced on semantic verbal fluency tasks, because the tendency to produce only the more typical members of various categories points to an impoverishment of semantic memory. The aim of our study was to compare in aMCI, AD, and control subjects a lexical (word frequency) and a lexical-semantic variable (item typicality) in a semantic verbal fluency task, and to evaluate the possible value of these variables in predicting conversion from aMCI to AD during a 2 years follow-up period. We found no difference in mean typicality of words produced by aMCI and AD subjects whereas both groups produced words of higher mean typicality than control subjects. Furthermore, to assess the relationship between typicality values and risk of conversion to AD, the aMCI group was split in two subgroups, including subjects who obtained a mean typicality value lower or higher than the median value of the whole aMCI group. Consistent with our hypothesis, conversion to AD was significantly more frequent in high typicality than in low typicality subjects.

The construct of mild cognitive impairment (MCI) has been proposed to identify patients at risk of developing Alzheimer's disease (AD) in the pre-clinical stage. Although subjects with MCI have an increased risk of progressing to dementia, most remain stable or return to normality. The new criteria for diagnosing prodromal AD assume that, to increase the predictive value of the MCI, in addition to a defect of delayed recall there must also be the presence of abnormal biomarkers, investigating structural and molecular neuroimaging and cerebrospinal fluid (CSF) analysis of amyloid-β or tau proteins. Although acknowledging that the use of CSF degeneration biomarkers is advisable not only for research, but also for clinical purposes, the present review is centered upon the neuropsychological markers of conversion to AD, which are equally clinically important. In particular, results of this review suggest the following: (a) measures of delayed recall are the best neuropsychological predictors of conversion from MCI to AD; (b) memory tests providing controlled encoding and cued recall are not necessarily better predictors than free recall tests; (c) stringent cut-off points are necessary to increase the specificity of these predictors; (d) multi-domain amnestic MCI patients are the best candidates for clinical trials, but not for treatment with disease-modifying drugs; and (e) not only episodic but also semantic memory is significantly impaired in patients who will convert to AD. These data and the underlying neural mechanisms will be discussed, trying to distinguish results obtained in MCI patients from those obtained in a pre-MCI stage of the AD progression.

The aim of this study was to investigate the neuronal network characteristics in physiological and pathological brain aging. A database of 378 participants divided in three groups was analyzed: Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal elderly (Nold) subjects. Through EEG recordings, cortical sources were evaluated by sLORETA software, while graph theory parameters (Characteristic Path Length λ, Clustering coefficient γ, and small-world network σ) were computed to the undirected and weighted networks, obtained by the lagged linear coherence evaluated by eLORETA software. EEG cortical sources from spectral analysis showed significant differences in delta, theta, and alpha 1 bands. Furthermore, the analysis of eLORETA cortical connectivity suggested that for the normalized Characteristic Path Length (λ) the pattern differences between normal cognition and dementia were observed in the theta band (MCI subjects are find similar to healthy subjects), while for the normalized Clustering coefficient (γ) a significant increment was found for AD group in delta, theta, and alpha 1 bands; finally, the small world (σ) parameter presented a significant interaction between AD and MCI groups showing a theta increase in MCI. The fact that AD patients respect the MCI subjects were significantly impaired in theta but not in alpha bands connectivity are in line with the hypothesis of an intermediate status of MCI between normal condition and overt dementia.

The occurrence of psychotic symptoms is common in Alzheimer's disease (AD), configuring a possibly distinguished clinical entity defined "Psychosis in Alzheimer's Disease" (AD-P). In order to investigate demographic clinical and biological variables potentially associated to the occurrence of AD-P, 148 AD patients were selected. Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) scores, socio-economic status and 5-HTTLPR and APOE gene polymorphisms were determined for each subject. AD-P patients were significantly more frequent carriers of the long (L) allele of 5-HTTLPR. The percentage of AD-P increased with the number of copies of the L-allele: 13% among S homozygote; 36% among heterozygotes; 51% among L-homozygotes. No difference resulted between AD-P and non-psychotic AD (AD-NP) in the distribution of the epsilon4 allele of APOE. The risk of AD-P was increased in L/L homozygous (OR = 7.25, p = 0.003) and, to a lesser extent, in heterozygous (OR = 3.91; p = 0.018). Backward logistic regression analysis showed that the risk for AD-P was increased in older subjects (OR = 1.07; p = 0.018) while an increase of MMSE score was protective (OR = 0.90; p = 0.004). The occurrence of AD-P resulted significantly related to age at examination, cognitive status, and to the presence of the 5-HTTLPR L-allele.