A Lack of Practice Effects on Memory Tasks Predicts Conversion to Alzheimer Disease in Patients With Amnestic Mild Cognitive Impairment.

The aim of the current study was to test the accuracy of practice effects, that is, improvement in test performance due to repeated neuropsychological evaluations, in identifying patients with amnestic mild cognitive impairment (a-MCI) at greater risk of conversion to Alzheimer disease (AD). For this purpose, we conducted a longitudinal study of 54 patients diagnosed with a-MCI at the first assessment and followed-up for 4 years. During this time, 18 patients converted to AD. Baseline and 6- to 12-month follow-up performances on a large set of neuropsychological tests were analyzed to determine their diagnostic ability to predict later conversion to dementia. Results demonstrate that a lack of practice effects on episodic memory tests is an accurate prognostic indicator of late conversion to AD in a-MCI patients. In fact, even though the performance of both groups was substantially comparable at the baseline evaluation, stable a-MCI patients greatly improved their memory performance at retest after 6 to 12 months; instead, scores of converter a-MCI remained stable or decreased passing from baseline to follow-up. Standardized z-change scores on memory tasks, which were computed as a reliable measure of performance change, classified group membership with very good overall accuracy, which was higher than the classification of converter and stable a-MCIs provided by baseline or follow-up scores. We hypothesize that the lack of practice effects on memory tasks mirrors the early involvement of medial temporal lobe areas in converter a-MCI that are fundamental for the consolidation of new memory traces.

Verbal and spatial memory spans in mild cognitive impairment.

OBJECTIVES: Working memory (WM) for verbal and visual material may be affected early in individuals with mild cognitive impairment (MCI). Verbal and visuospatial span tasks, that is neuropsychological procedures commonly used for the clinical assessment of WM, have been scarcely investigated in these patients. Therefore, this study was aimed at evaluating whether performance on tests of verbal and visual-spatial span (which rely to different extents on distinct components of the WM system) is differently sensitive to the presence of MCI and, in particular, of a preclinical AD condition in patients with MCI. MATERIALS & METHODS: 99 patients with amnesic MCI were given the Digit Span Forward (DSF) and Digit Span Backward (DSB) tests and the Corsi span task (CS) at baseline and were followed up for two years. 32 MCI patients converted to Alzheimer's disease (MCIc), but 67 patients did not deteriorate to meet the criteria for AD (MCIs). RESULTS: Results showed that although performance on DSF did not differ between groups, performance on DSB and CS and ratio indexes indicative of a performance decline passing from DSF to DSB and from DSF to CS significantly discriminated between a group of matched healthy controls and the overall group of MCI patients. Moreover, the ratio indexes significantly discriminated between MCIc and MCIs individuals. CONCLUSIONS: These data are consistent with the hypothesis that individuals with MCI, particularly those destined to convert to AD, are affected by reduced central executive resources even though the phonological loop is still functioning normally.

Does Cue Focality Modulate Age-related Performance in Prospective Memory? An fMRI Investigation.

How prospective memory (PM) weakens with increasing age has been largely debated. We hypothesized that automatic and strategic PM processes, respectively mediated by focal and non-focal cues, are differently affected by aging, even starting from 50-60 years of age. We investigated this issue using a 2 × 2 design in which focal and non-focal experimental conditions were created by varying the conjoint nature of the ongoing task (lexical decision vs. syllable matching tasks) and the PM cue (words vs. syllables). In the whole-brain analysis we found that the left inferior frontal gyrus and the middle cingulate cortex were more activated when young compared to older individuals performed a PM task; moreover, the anterior cingulate cortex was selectively activated during non-focal PM when the cues were words. In a region-of-interest analysis we observed that the medial and the lateral portions of the rostral prefrontal cortex were associated with the focal and non-focal conditions respectively, more in young than in older adults. Our findings provide evidence in support of early age-related differences in automatic/strategic PM functioning.

The Free Association Task: Proposal of a Clinical Tool for Detecting Differential Profiles of Semantic Impairment in Semantic Dementia and Alzheimer's Disease.

Backround and Objectives: It is widely agreed that patients suffering from Alzheimer's disease (AD) and patients suffering from semantic dementia (SD) might fail clinically administered semantic tasks due to a different combination of underlying cognitive deficits: namely, degraded semantic representations in SD and degraded representations plus executive control deficit in AD. However, no easy administrable test or test battery for differentiating the semantic impairment profile in these populations has been devised yet. Materials and Methods: In this study, we propose a new easy administrable task based on a free association procedure (F-Assoc) to be used in conjunction with category fluency (Cat-Fl) and letter fluency (Lett-Fl) for quantifying pure representational and pure control deficits, thus teasing apart the semantic profile of SD and AD patients. Results: In a sample of 10 AD and 10 SD subjects, matched for disease severity, we show that indices of asymmetric performance contrasting F-Assoc and each of the two verbal fluency tasks yield a clearly distinguishable discrepancy pattern across SD and AD. We also provide empirical support for the validity of an asymmetry measure contrasting F-Assoc and Cat-FL as an index of control impairment. Conclusions: The present study suggests that the free association procedure provides a pure measure of degradation of semantic representations avoiding the confound of possible concomitant executive deficits.

Naming famous people through face and voice: a normative study.

OBJECTIVES: Within the large topic of naming disorders, an important and separated chapter belongs to proper names. Defects of proper naming could be a selective linguistic problem. Sometimes, it includes names belonging to various kinds of semantically unique entities, but other times, it has been observed for famous people proper names only. According to Bruce and Young's model, different stages allow to recognize, identify, and name famous people from their faces and voices, subsuming different anatomical pathways, both in right temporal lobe, and their different efficiency in this task. The present study aimed to report the normative data concerning the naming of the same famous people from voice and face. SUBJECTS AND METHODS: One hundred fifty-three normal subjects underwent a test in which they were requested to name famous people from their face and from their voice. The stimuli belonged to the previously published Famous People Recognition Battery. RESULTS: The mean percentage score on naming from face was 84.42 ± 12.03% (range 55.26-100%) and the mean percentage score on naming from voice was 66.04 ± 16.81% (range 28.13-100%). The difference observed in performance by face and by voice resulted significant (t|153 = 15.973; p < 0.001). Regression analyses showed that the percentage score obtained on naming from faces was predicted by education, whereas naming from voice was predicted by education and gender. DISCUSSION: Naming from voice is more difficult than from face, confirming a different difficulty of the two tasks. Education showed high predicting value for faces and less for voices, whereas gender contributed to predict results only for voices.

Thalamocortical disconnection affects the somatic marker and social cognition: a case report.

Thalamo-cortical connectivity was characterised in a patient with bilateral infarct of the thalami, without evidence of cognitive deficits in everyday life. Patient underwent social and emotional tests, Iowa Gambling Task (IGT), with and without concomitant heart rate variability (HRV) recording and at 3T-MRI to assess thalamo-cortical connectivity. Patient showed impairment at the IGT, in somatic marker, in emotions and theory of mind. MRI documented a bilateral damage of the centromedian-parafascicular complex. Patient's thalamic lesions disconnected brain areas involved in decision-making and autonomic regulation, affecting the somatic marker and resulting in the neuropsychological deficit exhibited by L.C.

Famous people recognition through personal name: a normative study.

In this normative study, we investigated famous people recognition through personal name, using as stimuli the names of the same 40 Italian famous persons whose faces and voices had been utilized for the normative study of the Famous People Recognition Battery. For each famous people, we assessed name familiarity, person identification (when the name had been considered as familiar), and false alarms. The investigation was carried out on 143 normal subjects who varied in age and education. Name familiarity and semantic scores were affected by educational level, whereas age influenced false alarms. A comparison between results obtained with names in this research and with faces and voices of the same famous people in our previous study showed that familiarity scores were higher for personal names than those for faces and voices, which obtained the worst scores. Person identification scores were not significantly different from names and from faces, but both these scores were significantly higher than the semantic scores obtained by voices. Taken together, these results are inconsistent with the influential interactive activation and competition model of person recognition.

Accelerated Long-Term Forgetting Limited to the Recollection Component of Recognition Memory in a Temporal Lobe Epileptic Patient.

Accelerated long-term forgetting (ALF) is a frequent finding in patients with temporal lobe epilepsy (TLE). Here we report the case of a TLE patient who complained of marked difficulties in remembering personal events and information even though repeated neuropsychological assessments had failed to detect any deficit on common laboratory memory tests. The patient underwent an experimental investigation that involved estimating recollection and familiarity processes in the performance on verbal and visual recognition tests, over intervals ranging from 10 minutes to 7 days. Results showed accelerated forgetting confined to the recollection component only, which was particularly evident in the verbal test.

Recollection and familiarity components of recognition: effect of side of mesio-temporal damage.

We investigated the memory performance of three patients with unilateral mesio-temporal lobe damage with the aim of evaluating the roles of the left and right hemispheres in recollection and familiarity. Consistent with the "Material Specificity Hypothesis", the right brain-damaged individual was selectively poor on recollection and familiarity tests for faces. Conversely, left-lesioned patients were severely deficient in recollection and familiarity of verbal material but mildly deficient on visual-spatial tests. This partially unexpected finding is interpreted in light of the ability of humans to verbally recode almost any material, thus giving rise to left-hemisphere effects for nominally nonverbal stimuli.

Protecting cognition from aging and Alzheimer's disease: a computerized cognitive training combined with reminiscence therapy.

OBJECTIVE: The aim of this paper was to assess the efficacy of process-based cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and in healthy elderly (HE) subjects. METHODS: This multicenter, randomized, controlled trial involved 348 participants with mAD, MCI, and HE from four European countries. Participants were randomly assigned to two arms of a crossover design: those in arm A underwent 3 months of computerized pb-CT for memory and executive functions combined with RT and 3 months of rest; those in arm B underwent the reverse. The primary outcome was the effect of the training on memory and executive functions performance. The secondary outcome was the effect of the training on functional abilities in mAD assessed with the instrumental activities of daily living. RESULTS: We found a significant effect of the training for memory in all three groups on delayed recall of the Rey Auditory Verbal Learning Test and for executive functions in HE on the phonological fluency test. MCI and HE participants maintained these effects at follow-up. MCI and mAD participants also showed a significant effect of the training on the Mini-mental state examination scale. Participants with mAD showed more stable instrumental activities of daily living during the training versus the rest period. CONCLUSIONS: Our results corroborate the positive effect of pb-CT and its maintenance primarily on memory in HE and MCI participants that did not seem to be potentiated by RT. Moreover, our results are very promising for the mAD participants.

Recognition disorders for famous faces and voices: a review of the literature and normative data of a new test battery.

Several anatomo-clinical investigations have shown that familiar face recognition disorders not due to high level perceptual defects are often observed in patients with lesions of the right anterior temporal lobe (ATL). The meaning of these findings is, however, controversial, because some authors claim that these patients show pure instances of modality-specific 'associative prosopagnosia', whereas other authors maintain that in these patients voice recognition is also impaired and that these patients have a 'multimodal person recognition disorder'. To solve the problem of the nature of famous faces recognition disorders in patients affected by right ATL lesions, it is therefore very important to verify with formal tests if these patients are or are not able to recognize others by voice, but a direct comparison between the two modalities is hindered by the fact that voice recognition is more difficult than face recognition. To circumvent this difficulty, we constructed a test battery in which subjects were requested to recognize the same persons (well-known at the national level) through their faces and voices, evaluating familiarity and identification processes. The present paper describes the 'Famous People Recognition Battery' and reports the normative data necessary to clarify the nature of person recognition disorders observed in patients affected by right ATL lesions.

Selective Cognitive Dysfunction Is Related to a Specific Pattern of Cerebral Damage in Persons With Severe Traumatic Brain Injury.

OBJECTIVE: Cognitive dysfunction is a common sequela of traumatic brain injury (TBI); indeed, patients show a heterogeneous pattern of cognitive deficits. This study was aimed at investigating whether patients who show selective cognitive dysfunction after TBI present a selective pattern of cerebral damage. SETTING: Post-Coma Unit, IRCCS Santa Lucia Foundation, Rome, Italy. PARTICIPANTS: We collected data from 8 TBI patients with episodic memory disorder and without executive deficits, 7 patients with executive function impairment and preserved episodic memory capacities, and 16 healthy controls. DESIGN: We used 2 complementary analyses: (1) an exploratory and qualitative approach in which we investigated the distribution of lesions in the TBI groups, and (2) a hypothesis-driven and quantitative approach in which we calculated the volume of hippocampi of individuals in the TBI and control groups. MAIN MEASURES: Neuropsychological scores and hippocampal volumes. RESULTS: We found that patients with TBI and executive functions impairment presented focal lesions involving the frontal lobes, whereas patients with TBI and episodic memory disorders showed atrophic changes of the mesial temporal structure (hippocampus). CONCLUSION: The complexity of TBI is due to several heterogeneous factors. Indeed, studying patients with TBI and selective cognitive dysfunction should lead to a better understanding of correlations with specific brain impairment and damage, better follow-up of long-term outcome scenarios, and better planning of selective and focused rehabilitation programs.

Prospective memory performance of patients with Parkinson's disease depends on shifting aptitude: evidence from cognitive rehabilitation.

This study investigated the effect of cognitive training aimed at improving shifting ability on Parkinson's disease (PD) patients' performance of prospective memory (PM) tasks. Using a double-blind protocol, 17 PD patients were randomly assigned to two experimental arms. In the first arm (n=9) shifting training was administered, and in the second (placebo) arm (n=8), language and respiratory exercises. Both treatments consisted of 12 sessions executed over 4 weeks. PM and shifting measures (i.e., Trail Making Test and Alternate Fluency Test) were administered at T0 (before treatment) and T1 (immediately after treatment). A mixed analysis of variance was applied to the data. To evaluate the effects of treatment, the key effect was the interaction between Group (experimental vs. placebo) and Time of Assessment (T0 vs. T1). This interaction was significant for the accuracy indices of the PM procedure (p<.05) and for the performance parameters of the shifting tasks (p ≤.05). Tukey's HSD tests showed that in all cases passing from T0 to T1 performance significantly improved in the experimental group (in all cases p ≤.02) but remained unchanged in the placebo group (all p consistently>.10). The performance change passing from T0 to T1 on the Alternate Fluency test and the PM procedure was significantly correlated (p<.05). Results show that the cognitive training significantly improved PD patients' event-based PM performance and suggest that their poor PM functioning might be related to reduced shifting abilities.

Standardization and normative data obtained in the Italian population for a new verbal fluency instrument, the phonemic/semantic alternate fluency test.

The phonemic/semantic alternate fluency test seems to overcome some limits of the instruments currently used to assess set-shifting abilities. In particular, this test does not make high demands on motor systems because the subject is required to rapidly change mental set to generate words by continuously alternating between phonemic and semantic criteria. Thus, it is potentially feasible for use in individuals who have movement disorders. In this regard, some data support its sensitivity in revealing cognitive impairments in people suffering from frontal-striatal-related disorders. The first aim of this study was to provide standardization and normative data for the phonemic/semantic alternate fluency test. The second aim was to upgrade normative data for the single phonemic and semantic fluency tests. For these purposes, we administered to a sample of 335 healthy Italian subjects (ranging from 20 to 90 years), a test consisting of the following three subtests: (1) a single letter-cued (phonemic) fluency subtest; (2) a single category-cued (semantic) subtest; (3) a phonemic/semantic alternate fluency subtest. A composite shifting index was also derived to capture the shifting cost a subject pays passing from performance of the two single fluency subtests to performance of the alternate fluency subtest. We computed correction grids to adjust raw scores for age, literacy and gender according to the results of regression analyses. Moreover, we computed equivalent scores to permit direct and fast comparison of performance on the three fluency tests.

Low self-awareness of individuals with severe traumatic brain injury can lead to reduced ability to take another person's perspective.

Aims of this study were (i) to verify whether a deficit or a lack of self-awareness can lead to difficulties in assuming another person's perspective after a severe traumatic brain injury (TBI); (ii) to verify whether perspective-taking deficits emerge more from performance-based tasks than self-reports; and (iii) to evaluate the possible relationships between perspective-taking difficulties and some clinical, neuropsychological, neuropsychiatric, and neuroimaging variables. The Interpersonal Reactivity Index, Empathy Quotient, first-order false-belief, and faux pas written stories were administered to 28 patients with severe TBI and 28 healthy controls. The Awareness Questionnaire was also administered to TBI patients and their caregivers. Patients were split into 2 groups (impaired self-awareness vs adequate self-awareness) on the basis of the discrepancy Awareness Questionnaire score. Both TBI groups obtained lower scores than healthy controls on the Fantasy subscale of the Interpersonal Reactivity Index, the reality question of the false-belief stories, and the memory questions of the faux pas test. Only impaired self-awareness patients tended to obtain lower scores in first-order false-belief detection. Impaired self-awareness patients also performed significantly worse than both healthy controls and adequate self-awareness patients on the faux pas tasks. The analysis suggests a causal relationship between low self-awareness and perspective-taking difficulties in this population of patients.

Could Accelerated Long-Term Forgetting Be a Feature of the Higher Rate of Memory Complaints Associated with Subjective Cognitive Decline? An Exploratory Study.

Background: Recently, subjective cognitive decline (SCD) was proposed as an early risk factor for future Alzheimer's disease (AD). Objective: In this study, we investigated whether accelerated long-term forgetting (ALF), assessed with extended testing intervals than those adopted in clinical practice, might be a cognitive feature of SCD. Using an explorative MRI analysis of the SCD sample, we attempted to investigate the areas most likely involved in the ALF pattern. Methods: We recruited 31 individuals with SCD from our memory clinic and subdivided them based on their rate of memory complaints into mild SCDs (n = 18) and severe SCDs (n = 13). A long-term forgetting procedure, involving the recall of verbal and visuo-spatial material at four testing delays (i.e., immediate, 30 min, 24 h, and 7 days post-encoding) was used to compare the two sub-groups of SCDs with a healthy control group (HC; n = 16). Results: No significant between-group difference was found on the standard neuropsychological tests, nor in the immediate and 30 min recall of the experimental procedure. By contrast, on the verbal test severe SCDs forgot significantly more than HCs in the prolonged intervals (i.e., 24 h and 7 days), with the greatest decline between 30 min and 24 h. Finally, in the whole SCD sample, we found significant associations between functional connectivity values within some cortical networks involved in memory (default mode network, salience network, and fronto-parietal network) and verbal long-term measures. Conclusions: Our preliminary findings suggest that long-term forgetting procedures could be a sensitive neuropsychological tool for detecting memory concerns in SCDs, contributing to early AD detection.

The Role of the Anterior Thalamic Nuclei in the Genesis of Memory Disorders in Alzheimer's Disease: An Exploratory Study.

BACKGROUND: Increasing evidence is demonstrating that degeneration of specific thalamic nuclei, in addition to the hippocampus, may occur in Alzheimer's disease (AD) from the prodromal stage (mild cognitive impairment - MCI) and contribute to memory impairment. OBJECTIVE: Here, we evaluated the presence of macro and micro structural alterations at the level of the anterior thalamic nuclei (ATN) and medio-dorsal thalamic nuclei (MDTN) in AD and amnestic MCI (aMCI) and the possible relationship between such changes and the severity of memory impairment. METHODS: For this purpose, a sample of 50 patients with aMCI, 50 with AD, and 50 age- and education-matched healthy controls (HC) were submitted to a 3-T MRI protocol with whole-brain T1-weighted and diffusion tensor imaging and a comprehensive neuropsychological assessment. RESULTS: At macro-structural level, both the ATN and MDTN were found significantly smaller in patients with aMCI and AD when compared to HC subjects. At micro-structural level, instead, diffusion alterations that significantly differentiated aMCI and AD patients from HC subjects were found only in the ATN, but not in the MDTN. Moreover, diffusion values of the ATN were significantly associated with poor episodic memory in the overall patients' group. CONCLUSIONS: These findings represent the first in vivo evidence of a relevant involvement of ATN in the AD-related neurodegeneration and memory profile and strengthen the importance to look beyond the hippocampus when considering neurological conditions characterized by memory decline.

Exploring the neural and behavioral correlates of cognitive telerehabilitation in mild cognitive impairment with three distinct approaches.

Background: Currently, the impact of drug therapies on neurodegenerative conditions is limited. Therefore, there is a strong clinical interest in non-pharmacological interventions aimed at preserving functionality, delaying disease progression, reducing disability, and improving quality of life for both patients and their caregivers. This longitudinal multicenter Randomized Controlled Trial (RCT) applies three innovative cognitive telerehabilitation (TR) methods to evaluate their impact on brain functional connectivity reconfigurations and on the overall level of cognitive and everyday functions. Methods: We will include 110 participants with mild cognitive impairment (MCI). Fifty-five participants will be randomly assigned to the intervention group who will receive cognitive TR via three approaches, namely: (a) Network-based Cognitive Training (NBCT), (b) Home-based Cognitive Rehabilitation (HomeCoRe), or (c) Semantic Memory Rehabilitation Training (SMRT). The control group (n = 55) will receive an unstructured home-based cognitive stimulation. The rehabilitative program will last either 4 (NBTC) or 6 weeks (HomeCoRe and SMRT), and the control condition will be adapted to each TR intervention. The effects of TR will be tested in terms of Δ connectivity change, obtained from high-density electroencephalogram (HD-EEG) or functional magnetic resonance imaging at rest (rs-fMRI), acquired before (T0) and after (T1) the intervention. All participants will undergo a comprehensive neuropsychological assessment at four time-points: baseline (T0), within 2 weeks (T1), and after 6 (T2) and 12 months (T3) from the end of TR. Discussion: The results of this RCT will identify a potential association between improvement in performance induced by individual cognitive TR approaches and modulation of resting-state brain connectivity. The knowledge gained with this study might foster the development of novel TR approaches underpinned by established neural mechanisms to be validated and implemented in clinical practice.Clinical trial registration: [https://classic.clinicaltrials.gov/ct2/show/NCT06278818], identifier [NCT06278818].

Forward and backward span for verbal and visuo-spatial data: standardization and normative data from an Italian adult population.

The Digit span and Corsi span tasks are frequently used to assess verbal and visuo-spatial short-term memory. Forward versions of these tasks, in which sequences of items of increasing length have to be reproduced in the order they were presented, are believed to primarily evaluate the functioning of the working memory material-specific slave systems (i.e. the phonological loop and the visuo-spatial sketchpad for verbal and visuo-spatial data, respectively). The backward versions of both tasks, in which sequences of items have to be reproduced in the reverse order, are believed to primarily tax Central Executive resources. Here, we report normative data on the forward and backward versions of the Digit span and Corsi span tasks that was collected from 362 healthy Italians ranging in age from 20 to 90 years. The results show a decremental effect of age on performance in all tasks and an ameliorative effect of education in all tasks except the Corsi span backwards. We provide correction grids for age and literacy that derive from results of the regression analyses.

Mini mental Parkinson test: standardization and normative data on an Italian sample.

The mini mental Parkinson (MMP) is a test built to overcome the limits of the mini mental state examination (MMSE) in the short-time screening of cognitive disorders in individuals with Parkinson's disease (PD). In fact, in this scale, items tapping executive functioning are included to better capture PD-related cognitive changes. Some data sustain the sensitivity and validity of the MMP in the short neuropsychological screening of these individuals. Here, we report normative data on the MMP we collected on a sample of 307 Italian healthy subjects ranging from 40 to 91 years. The results document a detrimental effect of age and an ameliorative effect of education on the MMP total performance score. We provide for correction grids for age and literacy that derive from results of the regression analyses. Moreover, we also computed equivalent scores in order to allow a direct and fast comparison between the performance on the MMP and on other psychometric measures that can be administered to the subjects.