Recognition memory deficits in mild cognitive impairment

ABSTRACT There is no agreement on the pattern of recognition memory deficits characteristic of patients diagnosed with mild cognitive impairment (MCI). Whereas lower performance in recollection is the hallmark of MCI, there is a strong controversy about possible deficits in familiarity estimates when using recognition memory tasks. The aim of this research is to shed light on the pattern of responding in recollection and familiarity in MCI. Five groups of participants were tested. The main participant samples were those formed by two MCI groups differing in age and an Alzheimer's disease group (AD), which were compared with two control groups. Whereas one of the control groups served to assess the performance of the MCI and AD people, the other one, composed of young healthy participants, served the purpose of evaluating the adequacy of the experimental tasks used in the evaluation of the different components of recognition memory. We used an associative recognition task as a direct index of recollection and a choice task on a pair of stimuli, one of which was perceptually similar to those studied in the associative recognition phase, as an index of familiarity. Our results indicate that recollection decreases with age and neurological status, and familiarity remains stable in the elderly control sample but it is deficient in MCI. This research shows that a unique encoding situation generated deficits in recollective and familiarity mechanisms in mild cognitive impaired individuals, providing evidence for the existence of deficits in both retrieval processes in recognition memory in a MCI stage.     

Recognition memory deficits in mild cognitive impairment

ABSTRACT

There is no agreement on the pattern of recognition memory deficits characteristic of patients diagnosed with mild cognitive impairment (MCI). Whereas lower performance in recollection is the hallmark of MCI, there is a strong controversy about possible deficits in familiarity estimates when using recognition memory tasks. The aim of this research is to shed light on the pattern of responding in recollection and familiarity in MCI. Five groups of participants were tested. The main participant samples were those formed by two MCI groups differing in age and an Alzheimer's disease group (AD), which were compared with two control groups. Whereas one of the control groups served to assess the performance of the MCI and AD people, the other one, composed of young healthy participants, served the purpose of evaluating the adequacy of the experimental tasks used in the evaluation of the different components of recognition memory. We used an associative recognition task as a direct index of recollection and a choice task on a pair of stimuli, one of which was perceptually similar to those studied in the associative recognition phase, as an index of familiarity. Our results indicate that recollection decreases with age and neurological status, and familiarity remains stable in the elderly control sample but it is deficient in MCI. This research shows that a unique encoding situation generated deficits in recollective and familiarity mechanisms in mild cognitive impaired individuals, providing evidence for the existence of deficits in both retrieval processes in recognition memory in a MCI stage.     

Memory deficits for non-amnestic mild cognitive impairment

Non-amnestic mild cognitive impairment (naMCI) is one of the clinical subtypes of mild cognitive impairment (MCI). However, the characteristics of memory deficits in naMCI as assessed by clinical neuropsychological evaluations are not clear. In this study, a battery of neuropsychological tests was administered to 122 cognitively normal controls (NC), 133 amnestic mild cognitive impairment (aMCI) patients, and 72 naMCI patients. The results showed that in individuals with naMCI, episodic memory, and other cognitive domains were impaired. The Prospective Memory Test (PMT) event-based prospective memory (EBPM), the Symbol Digit Modalities Test (SDMT) Accidental Memory, Stick test (ST) visuoconstructional memory, and ST Working Memory were impaired, yet did not reach the level of aMCI. Semantic memory was affected to a degree comparable with aMCI. Some functions like Auditory Verbal Learning Test (AVLT) recognition, and Judgment of Confidence (JOC) were maintained, as well as PMT Time-Based Prospective Memory (TBPM). This study verified that memory impairment among individuals with naMCI was mainly in memory functions mediated by the frontotemporal cortex.     

Dissociations in visual attention deficits among persons with mild cognitive impairment

Impairments in visual attention and visual information processing have been identified as part of the neuropsychological features of Alzheimer's disease (AD), even in its earliest stages. There is increasing recognition that these deficits may be selective rather than global, with some attentional subtypes being more vulnerable than others. The few studies that have investigated attentional deficits in mild cognitive impairment (MCI), a putatively prodromal phase of AD, have not satisfactorily addressed the possible selectivity in attentional deficits in MCI. This study examined potential dissociations in visual attention deficits in MCI using a measure that assesses simple, divided, and selective attention. The results indicated a hierarchy of attentional impairments, with divided attention being the most affected and simple attention the least. Among participants with MCI, 53% showed evidence of impairment in divided attention compared to 19% of controls (OR = 4.81, p < .001). Poorer visual attention was also associated with poorer overall cognitive status. The implications of these findings for early identification of MCI, prevention of functional decline in MCI, and delay/reversal of cognitive degradation in MCI are discussed.     

Impaired verb fluency: a sign of mild cognitive impairment

We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive Impairment differed significantly from Subjective Cognitive Impairment and Alzheimer's disease. Reduced verb fluency thus appears to be a linguistic marker for incipient dementia. One possibility is that the verb fluency deficit in Mild Cognitive Impairment results from degenerative processes known to occur in the parahippocampal region.     

Spatial navigation deficits in amnestic mild cognitive impairment with neuropsychiatric comorbidity

Aims: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI).

Methods: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly participants (HE, n = 22). They completed the Mini-Mental State Examination and a virtual Hidden Goal Task in egocentric, allocentric, and delayed recall subtests.

Results: In allocentric navigation, aMCI and comMCI performed significantly worse than HE and similarly to each other. Although aMCI performed significantly worse at egocentric navigation than HE, they performed significantly better than patients with comMCI.

Conclusions: Despite the growing burden of dementia and the prevalence of neuropsychiatric symptoms in the elderly population, comMCI remains under-studied. Since trials often assess “pure” aMCI, we may underestimate patients’ navigation and other deficits. This finding emphasizes the importance of taking account of the cognitive effects of psychiatric disorders in aMCI.     

Alterations in working memory networks in amnestic mild cognitive impairment

Patients with amnestic mild cognitive impairment (aMCI) show preserved or mildly impaired working memory, despite their deficits in episodic memory. We aimed to identify performance and/or neural differences between aMCI patients and matched controls on a standard working memory fMRI task. Neuropsychological assessment demonstrated aMCI impairments in verbal and visual episodic long-term memory, with intact IQ and executive function. Participants completed a standard three-level N-back task where patients were unimpaired. Functional activations in the control group were found in expected areas, including the inferior parietal lobule and dorsolateral prefrontal cortex. Group differences were found in the insula and lingual gyrus and, in a region of interest analysis, in the hippocampus. In all cases, these were caused by an absence of task-related deactivations in the aMCI group. The results are consistent with reports of failure in task-related deacivations in aMCI and could be early indications of pathology.     

Focused attention deficits in patients with Alzheimer's disease and mild cognitive impairment

Reaction time (RT) tasks take various forms, and can assess psychomotor speed, (i.e., simple reaction time task), and focused attention (i.e., choice reaction time (CRT) task). If cues are provided before stimulus presentation (i.e., cued choice reaction time (CCRT) task), then a cueing effect can also be assessed. A limited number of studies have addressed the nature of focused attention impairments in Alzheimer's disease (AD). Additionally, it is unknown whether similar impairments occur in Mild Cognitive Impairment (MCI). The current study used three RT tasks to address the nature of focused attention impairments in AD and MCI subjects. The results suggest that there were significant CRT and CCRT differences in AD subjects when compared to NECs. Furthermore, slowed RTs were also present in the MCI group, which provides evidence for impaired focussed attention and the inability to benefit from a cue in both the MCI and AD groups. The implications of the impairments related to the MCI group could potentially prove useful in early diagnosis of cognitive impairments in the elderly.     

Knowledge and use of memory strategies in amnestic mild cognitive impairment

Despite the inclusion of memory strategy training in many interventions for amnestic mild cognitive impairment (aMCI), little research has directly examined knowledge and use of memory strategies in aMCI and their relationship to memory performance in order to guide the development of targeted interventions. The present study aimed to compare strategy knowledge and use between an aMCI and a healthy older adult (HOA) sample, and to determine the contribution of strategy knowledge and use to memory performance in each of these groups. The sample comprised 37 aMCI and 52 HOA participants aged over 60 years. All participants completed questionnaires to assess strategy knowledge and self-reported use of internal and external strategies in everyday life. In addition, strategy use was observed on the measures of retrospective and prospective memory performance (the CVLT-II and the CAMPROMPT). The aMCI group demonstrated decreased strategy knowledge and observed use of internal strategies, although equivalent observed use of external strategies compared with the HOA group. Furthermore, they reported equivalent use of both internal and external strategies. Observed use of strategies was significantly associated with retrospective memory performance for both groups and prospective memory performance for the aMCI group, supporting the inclusion of strategy training in interventions.     

On familiarity deficits in mild cognitive impairment: A reply to Migo and Westerberg

In this brief response to Migo and Westerberg we explain why we think that their criticism of our previous research showing familiarity deficits in mild cognitive impairment patients (MCI) is not sound. More concretely, we have replicated the effect several times previously, and we justify statistically the fact that in the previous paper we had to combine two MCI samples to demonstrate a reliable familiarity deficit. We note that there are several studies showing conflicting results. However, although the basis for these discrepancies remains uncertain, a new report has replicated the presence of deficits in familiarity, and more importantly, demonstrated its correlation with structural imaging biomarkers of Alzheimer’s disease.     

Recognition memory for emotional faces in amnestic mild cognitive impairment: An event-related potential study

ABSTRACT

This study examined the temporal course of emotional face recognition in amnestic mild cognitive impairment (aMCI). Patients and healthy controls (HC) performed a face recognition task, giving old/new responses to previously studied and novel faces displaying a negative or neutral expression. In aMCI patients, recognition accuracy was preserved for negative faces. Event-related potentials (ERPs) revealed disease-related changes in early perceptual components but not in ERP indices of explicit recognition. Specifically, aMCI patients showed impaired recognition effects for negative faces on the amplitudes of N170 and P2, suggesting deficient memory-related processing of negative faces at the stage of structural encoding and during an early recognition stage at which faces are individuated, respectively. Moreover, while a right-lateralized emotion effect specifically observed for correctly recognized faces on the amplitude of N170 was absent in aMCI, a similar emotion effect for successfully recognized faces on P2 was preserved in the patients, albeit with a different distribution. This suggests that in aMCI facilitated processing of successfully recognized emotional faces starts later in the processing sequence. Nonetheless, an early frontal old/new effect confined to negative faces and a parietal old/new effect unaffected by facial emotion were observed in both groups. This indicates that familiarity and conceptual priming processes may specifically contribute to recognition of negative faces in older adults and that aMCI patients can recruit the same retrieval mechanisms as controls, despite disease-related changes on early perceptual ERP components.     

Arousal enhanced memory retention is eliminated following temporal lobe resection

The amygdala, situated in the anterior medial temporal lobe (MTL), is involved in the emotional enhancement of memory. The present study evaluated whether anterior MTL-resections attenuated arousal induced memory enhancement for pictures. Also, the effect of MTL-resections on response latencies at retrieval was assessed. Thirty-one patients with unilateral MTL-resections (17 left, 14 right) together with 16 controls participated in a forced choice memory task with pictorial stimuli varying in arousal. Response latencies increased with stimulus arousal in controls but not in patients. This was paralleled by attenuated recognition memory for moderately and highly arousing pictures in MTL-resectioned patients as compared to healthy controls. However, patients and controls did not differ in memory performance for non-arousing pictures. These results suggest that the MTL is necessary for arousal induced memory enhancement.     

The NK3 receptor agonist senktide ameliorates scopolamine-induced deficits in memory for object, place and temporal order

Senktide, a potent neurokinin-3 receptor (NK₃-R) agonist, increases acetylcholine (ACh) release in the striatum, the prefrontal cortex (Schäble et al., 2011), the amygdala and hippocampus, presumably via postsynaptic mechanisms. A promnestic action of NK₃-R agonists has been described in a variety of learning/memory tasks. The memory-enhancing effects of NK₃-R agonists and their activating influence on ACh suggest a possible role of the NK₃-R in learning and memory via cholinergic modulation. Deterioration of the cholinergic system in the basal forebrain has been associated with learning and memory deficits and cholinergic agents have promnestic effects in a variety of learning paradigms. The anticholinergic drug, scopolamine, a muscarinic ACh receptor antagonist, incurs deficits in a variety of learning tasks and provides a useful tool to investigate the role of the cholinergic systems in mechanisms underlying learning and memory. The aim of this study was to ascertain the effect of the NK₃-R agonist, senktide, in the scopolamine-induced deficit model. We hypothesized that senktide treatment would attenuate scopolamine-induced (subcutaneous – s.c. 0.75 mg/kg) memory impairment in three novelty preference paradigms based on spontaneous object exploration: namely object recognition, object–place recognition and object recognition for temporal order. Administration of senktide reversed the scopolamine-induced memory deficits by re-establishing object recognition (s.c. 0.2 mg/kg), object–place recognition (0.2 and 0.4 mg/kg), as well as object recognition for temporal order (0.4 mg/kg) in adult Wistar rats. These results indicate memory enhancing effects of senktide in animals subjected to scopolamine-induced memory impairments and indicate that the promnestic action of NK₃-R agonists is mediated by muscarinic cholinergic mechanisms.     

A novel technique for the quantitative assessment of apraxic deficits: Application to individuals with mild cognitive impairment

The purpose of this study was to apply two novel quantitative assessments of apraxia to issues surrounding the cognitive profile of individuals with mild cognitive impairment (MCI) who are at increased risk of Alzheimer's disease (AD). In particular, it was wished to determine whether such quantitative assessment techniques can detect minor degrees of impairment at a stage in the putative disease process before apraxia has become clinically obvious. A total of 23 individuals with MCI and 75 healthy controls were assessed on two 3‐item sequential movement tasks involving either meaningful or meaningless actions. A traditional rating scale assessment of gesture‐to‐command was also administered. MCI patients took significantly longer than control subjects to complete the sequential movement tasks despite unimpaired performance on the traditional gesture production tasks. Furthermore, retrospective analyses revealed that, at the group level, only MCI patients who subsequently proceeded to a clinical diagnosis of AD were significantly slower than controls at the initial assessment. These findings provide the first evidence that the neuropsychological deficits associated with MCI may extend to the domain of praxic functions. Consequently, this work contributes to the growing literature questioning the clinical usefulness of the concept of MCI and the appropriateness of current diagnostic criteria for distinguishing this condition from mild AD.     

Hippocampal metabolites and memory performances in patients with amnestic mild cognitive impairment and Alzheimer's disease

In patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), previous studies have reported the decrease of N-acetylaspartate (NAA) concentration and the increase of myo-inositol (MI) concentration using proton magnetic resonance spectroscopy (1H-MRS). However, it remains to be investigated what aspects of cognition these metabolite changes reflect. In this study we evaluated the correlations between the subtests of Wechsler Memory Scale-Revised (WMS-R) and the concentrations of NAA and MI. The study group was composed of 42 patients with aMCI and 67 patients with AD. 1H-MR spectra with a single voxel-point resolved spectroscopy (PRESS) at a short echo time were acquired from the bilateral hippocampi and posterior cingulate gyrus. Positive correlations were shown between the NAA concentration in the left hippocampus and verbal memory, visual memory, general memory, attention and delayed recall; and furthermore, between the NAA concentration in the right hippocampus and verbal memory and general memory. Negative correlations were shown between the MI concentration in the left hippocampus and verbal memory, general memory, and delayed recall, and between the MI concentration in the right hippocampus and verbal memory. There was no significant correlation between any subtest of WMS-R and these two metabolite concentrations in the posterior cingulate gyrus. These findings suggest that bilateral, especially left hippocampal NAA and MI concentrations are associated with memory dysfunction observed in patients with aMCI and AD. In contrast, NAA and MI concentrations in the posterior cingulate gyrus may be less related to memory function than those in the hippocampus.     

Different storage and retrieval deficits in normal aging and mild cognitive impairment: a multinomial modeling analysis

The authors compared patients with mild cognitive impairment with healthy older adults and young control participants in a free recall test in order to locate potential qualitative differences in normal and pathological memory decline. Analysis with an extended multitrial version of W. H. Batchelder and D. M. Riefer's (1980) pair-clustering model revealed globally decelerated learning and an additional retrieval deficit in patients with mild cognitive impairment but not in healthy older adults. Results thus suggest differences in memory decline between normal and pathological aging that may be useful for the detection of risk groups for dementia, and they illustrate the value of model-based disentangling of processes and of multitrial tests for early detection of dementia.     

Increased sensitivity to proactive interference in amnestic mild cognitive impairment is independent of associative and semantic impairment

Episodic memory deficit is the hallmark of amnestic mild cognitive impairment (aMCI). There is, however, an overlap in performance among patients with aMCI and elderly controls (EC). The memory deficit in aMCI therefore needs to be better characterized. Studies have shown that associative memory is selectively impaired in aMCI, and recent work suggested that aMCI may be hypersensitive to semantic proactive interference (PI). It is not known whether this increased PI is related to associative or semantic impairment. EC (n = 44) and patients with aMCI (n = 30) performed two tasks presenting a gradually increasing PI effect across four lists. One task used semantic cueing, the other phonological cueing. We controlled for associative memory by introducing it as a covariate and by matching our subjects for it. Patients with aMCI had a greater PI effect than EC matched for associative memory, regardless of the type of cueing. The increased PI effect in patients with aMCI is independent of their associative and semantic impairment.     

Exploring mechanisms that affect retrograde memory for public events in amnestic mild cognitive impairment: A longitudinal update

Here, we examined mechanisms that affect retrograde memory in amnestic mild cognitive impairment (a-MCI) as a function of longitudinal clinical outcome. 8 a-MCI who converted to Alzheimer's dementia (AD) during the subsequent 3-year follow-up (converter a-MCI) and 10 a-MCI who remained clinically stable during the same period (stable a-MCI) were compared at the baseline evaluation (i.e., when they were diagnosed as a-MCI) using a remote memory questionnaire for public events that allows disentangling the differential contribution of storage and retrieval mechanisms to performance accuracy. Results suggest that deficits in remote memory are primarily explained by impaired retrieval abilities in stable a-MCI and by impaired storage in converter-to-AD a-MCI. This distinction between retrograde amnesia due to defective trace utilisation in stable a-MCI and trace storage in converter a-MCI is consistent with the temporal unfolding of declining anterograde memory over the course of disease progression to AD.     

Time perception and temporal order memory

The purpose of this research was to investigate the relation between the attentional resources underlying time perception and temporal order memory. Subjects made judgments about temporal attributes associated with a series of wordlists. Each word was displayed for 1.4 s, and the lists contained 10 words (14 s total), 15 words (21 s total), or 20 words (28 s total). Subjects judged either the list duration, the temporal order of the words, or both duration and temporal order. In addition, there were three mental workload conditions: control (no additional task requirements), and two mental arithmetic tasks (subtract 3 or subtract 7 from a series of random numbers). The results showed a pattern of bidirectional interference between timing and temporal order: the concurrent temporal order task interfered with duration judgments, and the concurrent timing task interfered with temporal order judgments. Bidirectional interference also occurred between the mental workload task and both duration judgments and temporal order judgments. The results indicate that duration and temporal order are closely related temporal attributes, and suggest that the processing of these attributes relies on a common set of executive attentional resources.