Search

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.

Background: The assessment of semantic memory may be a useful marker to identify individuals with mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD) in the early stages of the disease., Objective: The aim of this five-year follow-up longitudinal study is to assess whether semantic assessment could predict progression in MCI., Methods: A population of MCI (N = 251); mild (N = 178) and moderate AD (N = 114); and a sample of healthy participants (HP; N = 262) was investigated. The five-year follow-up of the MCI group was completed by 178 patients. Semantic and episodic memory measures were used, including a measure of the discrepancy between categorical and phonological verbal fluency, the semantic-phonological delta (SPD). The main outcome was the progression of MCI due to AD to dementia., Results: A general linear model showed a significant effect of diagnosis on SPD (Wilks' Lambda = 0.591; p < 0.001). The estimated marginal means were -0.91 (SE = 0.185) in HP, -1.83 (SE = 0.187) in MCI, -1.16 (SE = 0.218) in mild AD, and -1.02 (SE = 0.275) in moderate AD. Post-hoc comparisons showed a significant difference between MCI and HP (p < 0.001). The follow-up was completed by 178 MCI individuals. SPD in MCI patients who progress to dementia was significantly lower than in MCI that will not progress (p = 0.003). Together with the Mini-Mental State Examination, the SPD was the only measure with a significant predicting effect at the five-years follow-up (p = 0.016)., Conclusion: The SPD indicates the impairment of semantic memory in individuals with underlying AD at the MCI early stage, reflecting the early involvement of perirhinal and entorhinal cortices in the earliest stages of AD neuropathological process.

Electroencephalographic (EEG) rhythms are linked to any kind of learning and cognitive performance including motor tasks. The brain is a complex network consisting of spatially distributed networks dedicated to different functions including cognitive domains where dynamic interactions of several brain areas play a pivotal role. Brain connectome could be a useful approach not only to mechanisms underlying brain cognitive functions, but also to those supporting different mental states. This goal was approached via a learning task providing the possibility to predict performance and learning along physiological and pathological brain aging. Eighty-six subjects (22 healthy, 47 amnesic mild cognitive impairment, 17 Alzheimer's disease) were recruited reflecting the whole spectrum of normal and abnormal brain connectivity scenarios. EEG recordings were performed at rest, with closed eyes, both before and after the task (Sensory Motor Learning task consisting of a visual rotation paradigm). Brain network properties were described by Small World index (SW), representing a combination of segregation and integration properties. Correlation analyses showed that alpha 2 SW in pre-task significantly predict learning (r  =  -0.2592, p < 0.0342): lower alpha 2 SW (higher possibility to increase during task and better the learning of this task), higher the learning as measured by the number of reached targets. These results suggest that, by means of an innovative analysis applied to a low-cost and widely available techniques (SW applied to EEG), the functional connectome approach as well as conventional biomarkers would be effective methods for monitoring learning progress during training both in normal and abnormal conditions.

Taking into the account both the severity and the consistency of performances obtained on memory tests by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimer's disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles performances obtained at baseline in verbal (RAVLT) and visual episodic memory (Rey-Osterrieth Figure-delayed recall) and giving a score ranging from 1 (worst result) to 3 (best result) to results falling within each tertile. The EMS was computed for each patient by summing the tertile score obtained on each memory task, so that the total score ranged from 4 (worst performance) to 12 (best performance). The aMCI sample consisted of 198 subjects who completed the two-year follow-up, at the end of which 55 subjects had converted to dementia. The mean EMS score obtained by aMCI converters was significantly lower than that of aMCI-stable patients. In detecting conversion to dementia, the comparison between EMS and individual memory scores obtained at baseline was made by computing ROC curves, and estimating the respective area under the curve (AUC). The EMS had a larger AUC than the individual memory scores. At baseline aMCI converters performed worse than non-converters not only on memory tasks, but also on executive functions tasks. However, in a multiple variables logistic regression analysis in which all scores showing statistically significant differences between aMCI-converters and aMCI-stable were entered, the EMS was the only reliable predictor of progression from aMCI to dementia.

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.