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.

Forgetting of the recollection and familiarity components of recognition in patients with amnestic mild cognitive impairment.

INTRODUCTION: Patients with amnestic mild cognitive impairment (a-MCI) are deficient in storing memory traces relative to recollective forms of declarative memory. Controversial data have, instead, been reported concerning the storage of new memory traces relative to familiarity, with some studies reporting impairment and others sparing of the storage of this form of memory. No data have been reported concerning the consolidation of recollection and familiarity memory traces subsequent to their storage. METHODS: To investigate consolidation deficits resulting in accelerated forgetting of the memory trace, we submitted 16 patients with a-MCI and 19 age-matched normal controls (NC) to a verbal version of the experimental paradigm devised by Huppert and Piercy (1977, Neuropsychologia, 15, 643; 1978, Nature, 275, 317), which we modified to obtain a subjective judgement of the memory process (i.e., recollection or familiarity) for each remembered word that had prompted the 'old' response. The y/n recognition tests with a remember/know paradigm were given 10 min, 1 hr, and 24 hr after the study phase. RESULTS: Data demonstrated that patients with a-MCI forgot the memory traces relative to both the recollection and the familiarity components of recognition at the same rate as NC. CONCLUSIONS: Evidence was particularly strong for the familiarity component (where a-MCI patients scored the same as NC at all three delay intervals), but was less robust for the recollection data (where an equivalent forgetting rate across the three delay intervals could be demonstrated only for subgroups of a-MCI patients and NC who obtained comparable scores on the 10-min test).

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.

A Pilot Study on Brain Plasticity of Functional Connectivity Modulated by Cognitive Training in Mild Alzheimer's Disease and Mild Cognitive Impairment.

Alzheimer's disease (AD) alters the functional connectivity of the default mode network (DMN) but also the topological properties of the functional connectome. Cognitive training (CT) is a tool to slow down AD progression and is likely to impact on functional connectivity. In this pilot study, we aimed at investigating brain functional changes after a period of CT and active control (AC) in a group of 26 subjects with mild AD (mAD), 26 with amnestic mild cognitive impairment (aMCI), and a control group of 29 healthy elderly (HE) people. They all underwent a CT and AC in a counterbalanced order following a crossover design. Resting-state functional MRI and neuropsychological testing were acquired before and after each period. We tested post-CT and post-AC changes of cognitive abilities, of the functional connectivity of the DMN, and of topological network properties derived from graph theory and network-based statistics. Only CT produced functional changes, increasing the functional connectivity of the posterior DMN in all three groups. mAD also showed functional changes in the medial temporal lobe and topological changes in the anterior cingulum, whereas aMCI showed more widespread topological changes involving the frontal lobes, the cerebellum and the thalamus. Our results suggest specific functional connectivity changes after CT for aMCI and mAD.

Reducing Fall Risk with Combined Motor and Cognitive Training in Elderly Fallers.

BACKGROUND: Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between executive functions and gait abnormalities. The aim was to assess the effectiveness of a motor and a cognitive treatment developed within the EU co-funded project I-DONT-FALL. METHODS: In a sample of 481 elderly people at risk of falls recruited in this multicenter randomised controlled trial, the effectiveness of a motor treatment (pure motor or mixed with EFt) of 24 one-hour sessions delivered through an i-Walker with a non-motor treatment (pure EFt or control condition) was evaluated. Similarly, a 24 one-hour session cognitive treatment (pure EFt or mixed with motor training), delivered through a touch-screen computer was compared with a non-cognitive treatment (pure motor or control condition). RESULTS: Motor treatment, particularly when mixed with EFt, reduced significantly fear of falling (F(1,478) = 6.786, p = 0.009) although to a limited extent (ES -0.25) restricted to the period after intervention. CONCLUSIONS: This study suggests the effectiveness of motor treatment empowered by EFt in reducing fear of falling.

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.

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.

Sensitivity of a time-based prospective memory procedure in the assessment of amnestic mild cognitive impairment.

This study was aimed at evaluating whether prospective memory (PM) assessment is able to assist the discrimination between amnestic mild cognitive impairment (aMCI) and healthy subjects (HCs) and between aMCI with single versus multiple domains impairment. Individuals with aMCI and HCs were administered an extensive neuropsychological tests battery and a time-based PM task. PM scores significantly improved the accuracy of the regression model in discriminating between aMCI multiple domains, but not aMCI single domain, and HCs. Moreover, the prospective score significantly contributed to the discrimination between the two aMCI subgroups. These findings indicate the usefulness of including the PM procedure in evaluations of aMCI.

Recollection and familiarity in the human thalamus.

Recollection and familiarity are two distinct forms of recognition memory that differ in terms of the associative richness of the memory experience. In recollection, exposure to a previously encountered item cues the recollection of a number of contextual, temporal and other associative information. In the case of familiarity, instead, the item is recognized as previously encountered, but it does not cue any associative information. According to the dual-process theory, the memory processes that underlie recollection and familiarity are qualitatively different and this distinction is reflected in the existence of different neural substrates underlying the two processes. Thus far, research has primarily focused on distinct regions of the medial temporal lobe as implicated mostly in recollection (hippocampus) or familiarity (perirhinal cortex). Aggleton and Brown (1999) suggested extending the neuroanatomical distinction to other cortical and subcortical areas of the brain, including the thalamus. In particular, they proposed the existence of two reciprocally independent neural circuits for recollection and familiarity. The former would include the hippocampus, the fornix, the mammillary bodies and the anterior thalamic nuclei. The second would involve the mesial magnocellular portion of the mediodorsal nucleus connected to the perirhinal cortex through the ventroamygdalofugal pathway. Here we review neuropsychological evidence in experimental animals and brain-damaged individuals and functional neuroimaging evidence in healthy humans that supports Aggleton and Brown's model at the level of the thalamus. The evidence substantially supports the functional relationship between recollection processes and integrity of the thalamic anterior nuclei. Additional evidence, not predicted by the model, has been provided in favour of the reliance of recollection on the integrity of the lateral portion (parvocellular) of the mediodoral nucleus. Finally, there is sparse and controversial evidence in support of the reliance of familiarity on the integrity of the mesial portion of the mediodorsal nucleus, possibly due to neuroimaging methodological limits which did not satisfactorily distinguish between the medial and lateral portions of the mediodorsal nucleus.

Vascular thalamic amnesia: a reappraisal.

In humans lacunar infarcts in the mesial and anterior regions of the thalami are frequently associated with amnesic syndromes. In this review paper, we scrutinized 41 papers published between 1983 and 2009 that provided data on a total of 83 patients with the critical ischemic lesions (i.e. 17 patients with right-sided lesions, 25 with left-sided lesions and 41 with bilateral lesions). We aimed to find answers to the following questions concerning the vascular thalamic amnesia syndrome: (i) Which qualitative pattern of memory impairment (and associated cognitive and behavioral deficits) do these patients present? (ii) Which lesioned intrathalamic structures are primarily responsible for the amnesic syndrome? (iii) Are the recollection and familiarity components of declarative memory underlain by the same or by different thalamic structures? Results of the review indicate that, similar to patients with amnesic syndromes due to mesio-temporal lobe damage, patients with vascular thalamic amnesia display a prevalent deficit of declarative anterograde long-term memory, a less consistent deficit of declarative retrograde long-term memory and substantially spared short-term and implicit memory. Unlike mesio-temporal lobe patients, however, vascular thalamic amnesics often present dysexecutive and behavioral deficits similar to those observed in patients with frontal damage. The presence of an amnesic syndrome in patients with thalamic lacunar infarcts is strongly predicted by involvement of the mammillo-thalamic tract, which connects the anterior nuclei complex to the hippocampus proper via the fornix and the mammillary bodies. Finally, data reported in a few single cases provide support for the hypothesis that thalamic regions connected to distinct areas of the mesio-temporal lobe play differential roles in recollection and familiarity processes. The mammillo-thalamic tract/anterior nuclei axis seems primarily implicated in recollective processes, whereas the ventroamygdalofugal pathway/medio-dorsal axis primarily underlies familiarity processes.