Forgetting rate for the familiarity and recollection components of recognition in amnestic mild cognitive impairment: A longitudinal study.

Here we aimed to investigate the rate of forgetting of the familiarity and recollection components of recognition in patients at the onset of medial temporal lobe (MTL) pathology and destined to convert to Alzheimer's disease (AD). For this purpose, we conducted a longitudinal study of 13 patients who were diagnosed with amnestic mild cognitive impairment (a-MCI) at the first assessment and followed-up for 3 years. During this time, five patients converted to AD and eight remained in a stable condition of cognitive impairment. A group of 15 healthy subjects were enrolled as the control group (HC). In order to separately quantify the contribution of recollection and familiarity to recognition memory performance, the experimental sample was submitted to a modified version of Huppert and Piercy's procedure that included a Remember/Know paradigm. Data demonstrated that both stable and converter a-MCI patients forgot memory traces relative to the familiarity components of recognition at the same rate as HC. Conversely, converter a-MCI patients showed accelerated long-term forgetting specifically for the recollection component of recognition compared to stable a-MCI and HC. This is the first empirical demonstration that familiarity and recollection components of declarative memory are subject to different rates of forgetting in a-MCI patients as a function of their longitudinal clinical outcome. Our finding of accelerated long-term forgetting of the recollection component of recognition disclosed by converter a-MCI patients suggests that atrophy in the MTL not only interferes with the storage aspects but also disrupts the consolidation of memory traces.

Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data.

BACKGROUND: Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer's disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. METHODS: Following the initiative of the University of Washington's National Alzheimer's Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. RESULTS: Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. CONCLUSIONS: The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings.

Subjective clustering in patients with fronto-temporal dementia.

In the behavioral variant of frontotemporal dementia (bvFTD) memory deficits have been traditionally considered as due to difficulties in encoding/retrieval frontal strategies. However, the frontal origin of memory deficits in bvFTD has been questioned and hippocampal dysfunction has been also proposed. Here we analyzed bvFTD patients' proficiency in subjectively organizing memories without an external criterion. Twenty bvFTD patients and 20 healthy individuals were assessed with memory and executive tasks. The ability to subjectively organize memories in the immediate recall of a 15 unrelated word list was measured by calculating the index of subjective clustering (ISC) based on the constancies in response order across the five consecutive free recall trials. Results revealed reduced ISC in bvFTD patients with respect to normal controls. In the bvFTD group, the ISC score correlated with the Corsi span backward score and the number of categories achieved on the Modified Card Sorting Test. The bvFTD patients' reduced ISC and its correlation with executive performance suggest that executive deficits underlie their defective strategic organization of memories. However, as ISC did not predict memory accuracy in these patients, the memory deficit may not be the mere expression of their executive difficulties.

Memory for public events in amnestic mild cognitive impairment: The role of hippocampus and ventro-medial prefrontal cortex.

BACKGROUND: Current theories assume that retrograde memory deficits for semantic information in amnestic mild cognitive impairment (aMCI) are temporally graded and partially sparing most remote memories. Moreover, these models assume a prevalent role of the hippocampus in early phases of memory consolidation and of the prefrontal mesial neocortical areas in permanent consolidation of traces. PURPOSE: To explore the relationship between hippocampus and memory accuracy for the most recent public events and between the ventro-medial prefrontal cortex (vmPFC) and memory accuracy irrespective of the memory age, we investigated in aMCI patients the retrograde memory for public events and its relationship with grey matter volume reductions in the hippocampus and vmPFC. METHODS: 18 aMCI patients and 13 healthy subjects (HS) underwent a modified version of the Famous Events questionnaire (FEq) to assess their memory performance for public events. Patients underwent 3T-MRI scanning to assess correlations between FEq's scores and grey matter volumes. RESULTS: aMCI showed significantly reduced performances on FEq compared to HS in the recollection of most recent events, while no significant difference was observed for more remote memories, thus demonstrating a temporal gradient. Moreover, hippocampal volumes predicted accuracy scores for most recent, but not older, public events. Finally, an area in the subcallosal portion of the vmPFC, corresponding to BA32, predicted accuracy scores on FEq irrespective of the period examined. CONCLUSIONS: Pathological changes in a neural circuit linking hippocampal to medial prefrontal cortical regions are responsible for impaired recollection of retrograde memories in aMCI.

Implicit prototype learning in patients with memory deficit: Evidence from a study with Alzheimer's disease patients.

OBJECTIVE: In a previous study (Zannino et al., 2012), it was demonstrated that individuals with amnestic mild cognitive impairment (MCI) were unimpaired on a new prototype learning task consisting of morphed faces (face prototype learning task [FPLT]). This paradigm was devised to improve on the classical dot pattern task by ruling out any reliance on residual episodic memory or working memory resources. In the present study, we aimed to demonstrate: first, that people with even more severe episodic memory impairment than MCI are unimpaired on a fully implicit prototype learning task and second, that the dot pattern task, at variance with the FPLT, requires a no negligible contribution from the episodic memory system. METHOD: Twenty-four persons with Alzheimer's disease (AD) and 48 healthy controls took part in this experiment. As in the original study, in addition to the FPLT, they were also administered the classical dot pattern task and an ordinary forced-choice face recognition task. RESULTS: AD performed like normal controls in the FPLT but scored significantly worse on the dot pattern task and the face recognition task. Interestingly, although performance on the face recognition task did not correlate with that on the FPLT, a significant correlation was observed between the face recognition and the dot pattern task. CONCLUSIONS: Results support both of our claims: first, that also severe amnesic people can learn new visual prototypes with a fully implicit paradigm and, second, that the classical dot pattern task requires some degree of episodic resources. Further research is needed to rule out the role of working memory in solving the FPLT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.

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.

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.

Can Alzheimer's Disease Be Prevented? First Evidence from Spinal Stimulation Efficacy on Executive Functions.

BACKGROUND: Recently, a growing body of evidence has shown that, from the early stage of impairment, Alzheimer's patients (AD) present difficulties on a variety of tasks mostly relying on executive functions. These strongly impact their daily life activities causing a severe loss of independency and autonomy. OBJECTIVE: To evaluate the efficacy of transpinal direct current stimulation (tsDCS) combined with cognitive trainings for improving attentional and executive function abilities in a group of AD patients. METHODS: In a randomized-double blind design, sixteen AD patients underwent different cognitive trainings combined with tsDCS. During the treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (IX-X vertebrae) in two different conditions: 1) anodal, and 2) sham while performing three computerized tasks: alertness, selective attention, and executive functions. Each experimental condition was run in ten consecutive daily sessions over two weeks. RESULTS: After anodal tsDCS, a greater improvement in executive functions compared to sham condition was found. More importantly, the follow-up testing revealed that these effects lasted over 1 month after the intervention and generalized to the different neuropsychological tests administered before, after the treatment and at one month after the end of the intervention. This generalization was present also in the attentional domain. CONCLUSION: This evidence emphasizes, for the first time, that tsDCS combined with cognitive training results efficacious for AD patients. We hypothesize that enhancing activity into the spinal sensorimotor pathways through stimulation improved cognitive abilities which rely on premotor activity, such as attention and executive functions.

Recall and Recognition in Alzheimer's Disease and Frontotemporal Dementia.

BACKGROUND: It has long been debated whether performance on recall and recognition tests depends on the same or different memory systems and whether performance on these two tasks is dissociated in clinical populations. According to Dual process theories of recall, performance on recall and recognition tests dissociates in the relative reliance on frontal lobe related activities; in fact, the recall test requires more strategic retrieval of memoranda than the recognition task. By contrast, Dual process theories of recognition posit that performance on these tests differs in the relative contribution of recollection and familiarity memory processes in the two tasks: both recollection and familiarity contribute to recognition judgments, but only recollection supports recall performance. OBJECTIVE: The aim of this study was to clarify the cognitive processes involved in recall and recognition in patients with dementia. METHODS: We administered a 15-word recall task followed by a yes/no recognition paradigm to 28 patients with Alzheimer's disease (AD), 22 patients with the behavioral variant of frontotemporal dementia (bvFTD), and 45 normal controls (NCs). RESULTS: Results showed that on the delayed recall task, bvFTD patients performed much better than AD patients but the two groups did not differ on any index of recognition performance. CONCLUSION: The present data support the hypothesis that the performance of the two groups is expression of the different reliance on recollection (more impaired in the AD than in the bvFTD group) and familiarity (similarly impaired in the two groups) in performance on recall and recognition tasks.

Forgetting Rates on the Recency Portion of a Word List Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease.

Amnestic mild cognitive impairment has a greater risk of progressing to Alzheimer's disease (AD). Consistent with AD patients' distinctive deficit in consolidating new memory traces, in a recent study we demonstrated that the forgetting rate on the recency portion of a word list differentiates AD from other forms of dementia. In line with this finding, the aim of this study was to investigate whether increased recency forgetting could be a reliable index for predicting amnestic mild cognitive impairment (MCI) patients' conversion to AD. For this purpose, we compared accuracy in immediate and delayed recall from different portions of a word list in a group of patients with amnestic MCI who converted (C-MCI) or did not convert (S-MCI) to AD during a three-year follow-up period and in a group of normal controls. The results of the present study show that the forgetting from the recency portion of the list (operationalized as a ratio between immediate and delayed recall) was significantly larger in C-MCI than in S-MCI patients. Consistently, the hierarchical logistic regression analyses demonstrated that the recency ratio is a strong predictor of group membership. Similar to what occurs in full-blown AD patients, the results of our study suggest that the increased forgetting rate from the recency portion of the list in C-MCI patients is due to severely reduced efficiency in converting transitory short-term memory representations into stable long-term memory traces. This is consistent with prominent involvement of neuropathological changes in the cortical areas of the medial-temporal lobes and suggests that the recency ratio is a cognitive marker able to identify MCI patients who have a greater likelihood of progressing to AD.

The role of hippocampus in the retrieval of autobiographical memories in patients with amnestic Mild Cognitive Impairment due to Alzheimer's disease.

The role of the hippocampus and neocortical areas in the retrieval of past memories in pre-dementia Alzheimer's disease (AD) patients was investigated. The aim was to assess whether the hippocampus has a temporary role in memory trace formation, according to the Cortical Reallocation Theory (CRT), or whether it continuously updates and enriches memories, according to the Multiple Trace Theory. According to the former theory, hippocampal damage should affect more recent memories, whereas the association cortex is expected to affect memories of the entire lifespan. In the second case, damage to either the hippocampus or the association cortices should affect memories of the entire lifespan. Seventeen patients with amnestic Mild Cognitive Impairment due to AD were submitted to autobiographical (i.e., episodic and semantic personal) memory assessment. Patients underwent MRI for the acquisition of T1-weighted brain volumes. Voxel-based morphometry was used to assess correlations between grey matter (GM) volumes and autobiographical memory. Correlation analyses revealed a strict association between GM volumes in the hippocampus and patients' ability to retrieve the most recent but not the oldest autobiographical memories in both aspects, episodic and semantic. Moreover, patients' GM volumes in the pre-frontal and temporal polar areas were associated with recollection of episodic and semantic events, respectively. Finally, GM volumes in the precuneus and occipital cortex were associated with retrieval of the most recent episodic events. These findings indicate that the hippocampus has a specific time-dependent role; thus, they support the CRT.

Lost or unavailable? Exploring mechanisms that affect retrograde memory in mild cognitive impairment and Alzheimer's disease patients.

Retrograde amnesia has been largely documented in patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD). However, it is still not clear whether ineffectiveness in recalling past acquired information reflects loss of individual memory traces or failure to access specific stored traces. We aimed to disentangle the differential contribution of storage and retrieval processes to the pattern of retrograde amnesia in these patients. This issue was investigated in 18 a-MCI and 19 AD patients who were compared to 20 healthy controls. A novel questionnaire about public events was used; it consisted of two procedures (i.e., a free recall test and a true/false recognition test). Crucial differences emerged in the way the two groups of patients performed the experimental tasks. In fact, although both a-MCI and AD patients showed a similar pattern of impairment on the free recall test, a-MCI patients were able to normalise their performance on the recognition test, thus overcoming their deficits at the time of recall. Conversely, AD patients showed both reduced free recall ability and diminished sensitivity to benefit from recognition in recalling public events. Our findings suggest that the memory processes underlying RA were different for a-MCI and AD. Deficits in remote memory are prevalently explained by impaired retrieval abilities in a-MCI and by impaired storage in AD. This distinction between retrograde amnesia due to defective trace utilisation in a-MCI and trace storage in AD is consistent with the temporal unfolding of declining anterograde memory over the course of disease progression to AD.

Influence of controlled encoding and retrieval facilitation on memory performance of patients with subcortical ischemic vascular dementia and Alzheimer's disease.

Patients with subcortical ischemic vascular dementia (SIVD) perform better than Alzheimer's disease patients (AD) on the Free and Cued Recall Selective Reminding test (FCSRT). In this test, SIVD are able to overcome their strategic retrieval deficit, whereas AD patients, whose memory impairment is due to a hippocampal storage deficit, are not. However, the FCSRT does not assess the advantage passing from free to assisted learning, which is expected to be different in frontal and hippocampal damage. We compared SIVD, AD and healthy subjects on the free recall of a 15-word list not assisted at encoding and on the free and cued recall of the FCRST. Indexes of Encoding, Cueing and Total (measuring the advantage passing from the 15-word list free recall to the free and cued recall of the FCRST) were computed. The two groups performed comparably poorly on the free recall of the 15-word list, but SIVD outperformed AD patients in the free and cued recall of the FCSRT and took greater advantage than AD patients on both learning and recall when passing from the unassisted to the assisted paradigms. All indexes significantly predicted diagnostic group membership, but the Total Index showed the larger classification accuracy with 80% of AD and 71% of SIVD correctly classified. These results confirm that the FCRST is able to differentiate AD and SIVD patients with a good level of accuracy. However, the evaluation of memory performance variation as a function of support to encoding provides additional data able to increase diagnostic reliability.

Predicting progression to Alzheimer's disease in subjects with amnestic mild cognitive impairment using performance on recall and recognition tests.

The research of reliable procedures for predicting cognitive decline or stability in persons with amnestic mild cognitive impairment (a-MCI) is a major goal for the early identification of subjects in the prodromal stages of dementia. The aim of this study was to evaluate whether different memory performances on two procedures commonly used for the neuropsychological assessment of episodic memory (i.e., free recall and recognition) might be a key in predicting a-MCI patients' subsequent progression to Alzheimer's disease (AD). For this purpose, 80 patients diagnosed with a-MCI at the first assessment and followed-up for at least 3 years were included. During this time, 41 subjects remained in a stable condition of cognitive impairment or improved (stable-MCI) and 39 patients converted to AD dementia (converter-MCI). Sixty-two age- and education-matched healthy individuals were also recruited as healthy controls (HC). Baseline memory performance on the free recall (5th immediate and 15-min delayed) and yes/no recognition (the sensitivity measure d') of a 15-word list were analyzed. Results showed that stable-MCIs forgot significantly more information from immediate to delayed recall of the word list than HC, but exhibited a pronounced improvement of memory performance in the recognition test format. On the contrary, converter-MCIs showed diminished sensitivity in benefiting from cues for recognizing studied words. Word list recognition correctly classified group membership with good overall accuracy, which was higher compared to the classification of converter and stable a-MCIs provided by free recall; therefore, it could be a useful diagnostic tool for predicting progression to AD dementia from the prodromal stage.

The attribute priming effect in patients with Alzheimer's disease.

Experiments with semantic priming (SP) paradigms have documented early hypopriming in patients with AD when concepts are used as primes and attribute concept features as targets, suggesting that concept attributes are vulnerable to damage very early in the disease course. The aims of this study were to confirm early priming reduction in the attribute condition in patients with AD and to determine which of several semantic indexes (such as the level of distinctiveness, correlation or feature dominance of concept features) best predicts the priming effect size in AD. We administered an SP attribute condition paradigm to 20 mildly demented patients with AD and to 10 NCs. We used concept-attribute pairs for which normative data of semantic indexes relative to both concept primes (i.e., number, type, mean level of dominance, distinctiveness and correlation of features constituting the concepts) and target features (i.e., level of feature dominance, correlation and distinctiveness) were available. Results showed that compared to NCs, the AD group obtained very reduced priming facilitation. Furthermore, the item regression analyses showed that the priming decrement in the AD group was predicted by the feature dominance of the target in the related pairs; that is, the lower the target feature dominance, the lower the priming effect elicited. These results confirmed hypopriming in the attribute condition from the very early phase of AD and support the view that attributes which are more salient for the identification of a given concept are also those most resistant to semantic memory degradation in AD pathology.

Forgetting Rate on the Recency Portion of a Word List Differentiates Mild to Moderate Alzheimer's Disease from Other Forms of Dementi.

Patients with Alzheimer's disease (AD) demonstrate a disproportionately larger forgetting rate in episodic memory tasks. Previous studies documented that, in comparison with healthy controls, the increased forgetting manifested by AD patients in word list recall tasks is confined to the recency portion of the list with normal forgetting rates on the primacy and mid-list portions. In this study we compared the primacy, mid-list, and recency ratios, obtained by dividing the immediate and delayed recall of words in position 1-4, 5-11, and 12-15 of a 15-word list, in different groups of demented patients, i.e., AD, frontal variant of frontotemporal dementia (fvFTD), Lewy body disease (LBD), subcortical ischemic vascular dementia (SIVD), and a group of normal controls (NC). The aim was to investigate whether the above reported forgetting pattern would differentiate AD performance from that of other dementia groups. Results of the statistical analysis showed that only the recency ratio differentiated AD from patients in the other dementia groups. Consistently, hierarchical logistic regression analyses demonstrated that the recency ratio discriminated between AD patients and individuals affected by other forms of dementia. In particular, the discrimination power was high in differentiating AD from fvFTD patients but was less accurate in differentiating AD from LBD and SIVD patients. We assume that the increased forgetting in AD patients is due to a deficit in memory consolidation mechanisms (specific to AD) that prevent the terminal items in a list from being transferred from a temporary short-term memory store to a stable long-term memory store.