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.     

Visual Imagery Processing and Knowledge of Famous Names in Alzheimer's Disease and MCI

ABSTRACT

The study of memory for famous people and visual imagery retrieval was investigated in patients in the early stages of Alzheimer's disease (AD) and in the prodromal stage of AD, so-called Mild Cognitive Impairment (MCI). Fifteen patients with AD (MMSE ≥23), 15 patients with amnestic MCI (a-MCI) and 15 normal controls (NC) performed a famous names test designed to evaluate the semantic and distinctive physical features knowledge of famous persons. Results indicated that patients with AD and a-MCI generated significantly less physical features and semantic biographical knowledge about famous persons than did normal control participants. Additionally, significant differences were observed between a-MCI and AD patients in all tasks. The present findings confirm recent studies reporting semantic memory impairment in MCI. Moreover, the current findings show that mental imagery is lowered in a-MCI and AD and is likely related to the early semantic impairment.     

Memory factors in Rey AVLT: Implications for early staging of cognitive decline

Supraspan verbal list learning is widely used to assess dementia and related cognitive disorders where declarative memory deficits are a major clinical sign. While the overall learning rate is important for diagnosis, serial position patterns may give insight into more specific memory processes in patients with cognitive impairment. This study explored these patterns in a memory clinic clientele. One hundred eighty three participants took the Rey Auditory‐Verbal Learning Test (RAVLT). The major groups were patients with Alzheimer's disease (AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the five trials and five serial partitions were factor analysed. Three memory factors were found and interpreted as Primacy, Recency, and Resistance to Interference. AD and MCI patients had impaired scores in all factors. SCI patients were significantly impaired in the Resistance to Interference factor, and in the Recency factor at the first trial. The main conclusion is that serial position data from word list testing reflect specific memory capacities which vary with levels of cognitive impairment.     

Chronic sodium azide treatment impairs learning of the Morris water maze task.

A reduction in the activity of cytochrome oxidase, a respiratory chain enzyme, has been recently identified in mitochondria from blood platelets and postmortem brain tissue from Alzheimer's disease (AD) patients. We have developed an animal model of this deficit in rats by chronic subcutaneous infusion of sodium azide, a selective inhibitor of cytochrome oxidase, delivered via Alzet 2ML4 osmotic minipumps. In previous work, azide-treated rats were impaired in an appetitively motivated spatial learning task, the radial arm maze. In the present investigation, we tested male Sprague-Dawley rats (350-400 g), which were tonically infused with azide or saline, on an aversively motivated spatial task, the Morris water maze. Azide-treated rats were impaired on both acquisition and retention of this task, without showing evidence of a motor impairment. Thus, the present results are consistent with previous findings showing that chronic azide treatment produces a learning and memory deficit. These findings strengthen the hypothesis that azide treatment in rats produces a useful animal model of some aspects of AD.     

Category Cued Recall Following Controlled Encoding as a Neuropsychological Tool in the Diagnosis of Alzheimer’s Disease: A Review of the Evidence

Aim of the present review paper was to evaluate the hypothesis (included in the proposal of new research criteria for Alzheimer’s disease; Dubois et al., Lancet Neurology, 6, 734–746, 2007) that a neuropsychological tool which provides support for the semantic encoding of memorandum at the time of study and supplies category cues at the time of retrieval (i.e. the Grober-Buschke paradigm) is more effective than traditional measures of free recall in 1) differentiating patients affected by the amnestic form of Mild Cognitive Impairment (MCI) or by mild to moderate forms of Alzheimer’s disease (AD) from healthy matches, 2) predicting the conversion of individuals with MCI to AD, and 3) differentiating AD patients from individuals affected by other forms of dementia. Results of the review are controversial regarding the superiority of the Grober-Buschke procedure in differentiating individuals affected by AD or MCI from healthy individuals. The only study that evaluated this issue directly found that the Grober-Buschke procedure was more sensitive and specific than more traditional memory tests in predicting the conversion of MCI patients to AD. Finally, two studies reported that patients affected by AD or other forms of dementia showed different performance patterns in the free and cued recall tasks of the Grober-Buschke procedure. In conclusion, although encouraging results are reported in the few studies that investigated the ability of this procedure to predict the evolution of individuals with amnestic MCI and to differentiate AD patients from patients with other forms of cortical and subcortical dementia, more experimental work is needed to confirm these positive findings.     

Differential Memory Test Sensitivity for Diagnosing Amnestic Mild Cognitive Impairment and Predicting Conversion to Alzheimer's Disease

ABSTRACT

Episodic memory is the first and most severely affected cognitive domain in Alzheimer's disease (AD), and it is also the key early marker in prodromal stages including amnestic mild cognitive impairment (MCI). The relative ability of memory tests to discriminate between MCI and normal aging has not been well characterized. We compared the classification value of widely used verbal memory tests in distinguishing healthy older adults (n = 51) from those with MCI (n = 38). Univariate logistic regression indicated that the total learning score from the California Verbal Learning Test-II (CVLT-II) ranked highest in terms of distinguishing MCI from normal aging (sensitivity = 90.2; specificity = 84.2). Inclusion of the delayed recall condition of a story memory task (i.e., WMS-III Logical Memory, Story A) enhanced the overall accuracy of classification (sensitivity = 92.2; specificity = 94.7). Combining Logical Memory recognition and CVLT-II long delay best predicted progression from MCI to AD over a 4-year period (accurate classification = 87.5%). Learning across multiple trials may provide the most sensitive index for initial diagnosis of MCI, but inclusion of additional variables may enhance overall accuracy and may represent the optimal strategy for identifying individuals most likely to progress to dementia.     

Production and identification repetition priming in amnestic mild cognitive impairment

The experiment reported here examined implicit memory function, as measured through repetition priming, in amnestic mild cognitive impairment (MCI) to examine whether impairments exist in this aspect of memory function. Young adults, healthy older controls, Alzheimer's disease patients, and MCI participants were asked to perform two types of implicit memory tests (word stem completion and threshold identification repetition priming tasks), as well as a recognition test for studied items. As expected, young adults performed better than the other participants on the recognition test and the word stem completion task; there was equivalent priming across groups on the word identification task. While both the older control and MCI participants showed lower levels of priming on the word stem completion task relative to the young adults, the magnitude of priming was equivalent for these two groups, and reliably greater than that of the dementia participants. These results suggest that not all aspects of memory function are impaired in MCI relative to healthy aging.     

Differential effects of post-training muscimol and AP5 infusions into different regions of the cingulate cortex on retention for inhibitory avoidance in rats.

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in four different coordinates of the cingulate cortex: (1) the anterior cingulate (AC), (2) the rostral region of the posterior cingulate (RC), (3) the upper portion of the caudal region of the posterior cingulate (UC), and (4) the lower portion of the caudal region of the posterior cingulate (LC). After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock). Either immediately, or 90 or 180 min after training, animals received a 0.5-microl infusion of vehicle (phosphate buffer, pH 7.4), of muscimol (0.5 microg), or of AP5 (5.0 microg). Retention testing was carried out 24 h after training. Muscimol was amnestic when given into any of the three coordinates of the posterior cingulate cortex 90 min after training, and when given into LC immediately post-training. In addition, AP5 was amnestic when given into UC 90 min post-training, but not when given into any other region and/or at any other time. None of the treatments had any effect when given into AC. The results suggest that memory processing of the inhibitory avoidance task is regulated by the posterior but not by the anterior cingulate cortex, through muscimol-sensitive synapses, relatively late after training. AP5-sensitive synapses appear to play a very limited role in these processes, restricted to UC.     

Production and Identification Repetition Priming in AmnesticMild Cognitive Impairment

ABSTRACT

The experiment reported here examined implicit memory function, as measured through repetition priming, in amnestic mild cognitive impairment (MCI) to examine whether impairments exist in this aspect of memory function. Young adults, healthy older controls, Alzheimer's disease patients, and MCI participants were asked to perform two types of implicit memory tests (word stem completion and threshold identification repetition priming tasks), as well as a recognition test for studied items. As expected, young adults performed better than the other participants on the recognition test and the word stem completion task; there was equivalent priming across groups on the word identification task. While both the older control and MCI participants showed lower levels of priming on the word stem completion task relative to the young adults, the magnitude of priming was equivalent for these two groups, and reliably greater than that of the dementia participants. These results suggest that not all aspects of memory function are impaired in MCI relative to healthy aging.     

Activation of adenosine receptors in the posterior cingulate cortex impairs memory retrieval in the rat

Adenosine A1 and A2A receptor agonists and antagonists have been reported to alter learning and memory. The aim of our study was to investigate the involvement of adenosinergic system in memory retrieval into posterior cingulate cortex (PCC) of Wistar rats. To clarify this question, we tested specifics agonist and antagonists of adenosine A1 and A2A receptors in rats submitted to a one-trial inhibitory avoidance task. The stimulation of adenosine A1 and A2A receptors by CPA and CGS21680, respectively, impaired memory retrieval for inhibitory avoidance task, into PCC. These findings provide behavioral evidence for the role of adenosinergic system in the memory retrieval into PCC.     

The occurrence of different intrusive errors in patients with Alzheimer's disease, multiple cerebral infarctions, and major depression.

Recent evidence suggests that specific types of intrusive errors may occur more often in the protocols of Alzheimer's disease (AD) patients than in those of patients diagnosed with other types of dementia. Using the FULD Object Memory Evaluation, we documented the occurrence of five qualitatively different types of intrusive errors for mildly and moderately impaired patients with AD and multiple cerebral infarctions (MCI). Depressed and normal elderly controls were also studied. Despite an equivalent degree of impairment on a broad array of neuropsychological measures, mildly impaired AD patients evidenced greater deficits on a measure tapping retrieval from semantic memory and demonstrated a higher occurrence of specific types of intrusive errors relative to their mildly impaired MCI counterparts. Further, both of these measures were highly correlated, suggesting that these indices may be particularly sensitive to semantic dysfunction associated with early AD.     

认知和情绪冲突的监控与解决：来自轻度认知损伤的证据

轻度认知损伤(mild cognitive impairment, MCI)是介于正常老化和痴呆之间的过渡阶段。近年来, 执行控制的损伤被认为是MCI的核心特征之一。当前, 在MCI执行控制的领域内, 对冲突监控与解决的特征及其神经机制的研究较少。本研究拟通过认知及情绪冲突实验范式, 结合脑成像技术, 探讨遗忘型MCI (amnestic MCI, aMCI)认知和情绪冲突的监控与解决的特征及相应的脑激活模式; 通过对比aMCI和正常老年人在认知和情绪冲突任务中激活的神经环路, 考察aMCI是否在执行加工的神经网络上存在激活异常。在上述研究基础上, 研究者拟探讨aMCI在执行控制的冲突监控与解决上是否存在一般性的损伤机制, 同时试图寻找aMCI在执行控制的冲突监控与解决方面的认知及神经生物学标记。这对深入理解痴呆的发病进程并有针对性的开展痴呆的早期识别与干预具有重要的理论意义和实践意义。     

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.     

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.     

Spatial Working Memory in Aging and Mild Cognitive Impairment: Effects of Task Load and Contextual Cueing

ABSTRACT

Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression.     

Social cognition and social functioning in patients with amnestic mild cognitive impairment or Alzheimer’s dementia

The aim of the present study was to examine social cognition and social functioning in a group of amnestic mild cognitive impairment (aMCI) and Alzheimer’s dementia (AD) patients. Thirty one people with aMCI, 29 individuals with AD, and 45 healthy older adults participated in the study. Facial expressions of happiness, anger, fear, disgust, and surprise presented in different intensities had to be labelled. Mentalizing was assessed using first-order belief theory of mind (ToM) stories and everyday social functioning by the Inventory of Interpersonal Situations (IIS), completed by an informant. aMCI patients were impaired in recognizing the emotions anger, disgust, and fear, while AD patients were impaired in recognizing the emotions anger, disgust, and surprise. More importantly, no significant differences between aMCI and AD patients were found on overall emotion recognition. Both the aMCI and AD patients were impaired on the ToM task, but no differences between the aMCI and AD patients were found. On everyday social functioning, only the AD patients showed impairments. No associations between the IIS and ToM were found, but the IIS and emotion perception were significantly correlated. Regression analysis taking all potentially confounding variables into account showed that only mood, but not the social-cognitive task performance or any other cognitive variable, predicted social functioning. aMCI and AD patients demonstrated impairments in mentalizing and facial emotion perception, and showed decrements in everyday social functioning. Informing caregivers about these deficits may help them to understand deficits in social cognition that may be present already in the MCI stage of Alzheimer’s disease.     

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.     

Memory profiling in mild cognitive impairment: Can we determine risk for Alzheimer's disease?

Mild cognitive impairment (MCI) is considered a transitional stage between normal ageing and Alzheimer's disease (AD), but not all MCI cases progress to AD and there has been limited focus on how to identify who will progress. Given claims for a characteristic kind of memory impairment in AD involving deficits in encoding and consolidation of information, we propose that ‘memory profiling’ of individuals with MCI may help identify which individuals will progress. We initially set out to establish whether the same characteristic memory profile was present prior to the onset of AD (preAD). Very few studies provided data that allowed us to examine this, but results tentatively supported an encoding/consolidation profile in preAD. A single study tested the clinically important contrast of preAD versus non‐preAD MCI cases and found no difference under any condition or in memory profiles, but interpretation of the findings is limited by short duration of follow‐up, ceiling effects, and task limitations in assessing more complex and qualitative aspects of memory. Although existing data lead to equivocal conclusions, we believe that memory profiling is an endeavour worth pursuing, particularly given the increasing number of people with MCI presenting for clinical assessment. We propose that tests designed specifically to measure memory processes should be sensitive to preAD and are required in prospective longitudinal designs to identify these clinically crucial MCI cases.     

An evaluation of recollection and familiarity in Alzheimer’s disease and mild cognitive impairment using receiver operating characteristics

There is a need to investigate exactly how memory breaks down in the course of Alzheimer’s disease (AD). Examining what aspects of memorial processing remain relatively intact early in the disease process will allow us to develop behavioral interventions and possible drug therapies focused on these intact processes. Several recent studies have worked to understand the processes of recollection and familiarity in patients with mild cognitive impairment (MCI) and very mild AD. Although there is general agreement that these patient groups are relatively unable to use recollection to support veridical recognition decisions, there has been some question as to how well these patients can use familiarity. The current study used receiver operating characteristic (ROC) curves and a depth of processing manipulation to understand the effect of MCI and AD on the estimates of recollection and familiarity. Results showed that patients with MCI and AD were impaired in both recollection and familiarity, regardless of the depth of encoding. These results are discussed in relation to disease pathology and in the context of recent conflicting evidence as to whether familiarity remains intact in patients with MCI. The authors highlight differences in stimuli type and task difficulty as possibly modulating the ability of these patients to successfully use familiarity in support of memorial decisions.