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.     

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.     

Practice effects on motor control in healthy seniors and patients with mild cognitive impairment and Alzheimer's disease

This research was designed to test the hypothesis that motor practice can enhance the capabilities of motor control in healthy controls (NC) and patients with a diagnosis of probable Alzheimer's disease (AD) and mild cognitive impairment (MCI), and consequently results in better motor performance. Approximately half of the subjects in the NC (n = 31), AD (n = 28), and MCI (n = 29) either received or did not receive practice on a task of fast and accurate arm movement with a digitizer. Changes in movement time (MT), movement smoothness (jerk), and percentage of primary submovement (PPS) were recorded and compared among the three groups across six blocks of trials (baseline and five training sessions). For all subjects, practice improved motor functions as reflected by faster and smoother motor execution, as well as a greater proportion of programming control. Compared to unaffected matched controls, AD and MCI subjects exhibited a greater reduction in movement jerk due to practice. Movement time and PPS data revealed that motor practice appeared to reduce the use of "on-line" correction adopted by the AD or MCI patients while performing the aiming movements. Evidently, their arm movements were quicker, smoother, and temporally more consistent than their untrained peers. The findings of this study shed light on how MCI and AD may affect motor control mechanisms, and suggest possible therapeutic interventions aimed at improving motor functioning in these impaired individuals.     

The usefulness of the story recall test in patients with mild cognitive impairment and Alzheimer's disease

ABSTRACT

Background: The story recall test (SRT) is one of the most reliable neuropsychological assessments for evaluating verbal memory function in order to distinguish between individuals with normal aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD). The SRT is analogous to the logical memory test in Wechsler Memory Scale-III, which has recently been developed and standardized to apply to older adults in Korea. The purpose of this study was to examine the usefulness of the SRT and its ability to discriminate between normal cognitive aging and patients with MCI or AD. Methods: One hundred and twelve patients with MCI, 97 patients with AD, and 53 healthy elderly adults participated in this study. The SRT was compared with the Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Korean version of the Mini Mental State Examination (K-MMSE), and the Korean version of the Hopkins Verbal Learning Test (K-HVLT). Results: The SRT was well-correlated with the dementia rating scales and the K-HVLT. However, the sensitivity and specificity of the SRT was greatly influenced by the level of education of the subjects. Conclusions: The SRT is a sensitive measurement of verbal memory function that can be used in clinical settings to discriminate between normal memory functioning and the very early and moderate stages of AD in a Korean population. Moreover, it is important to recognize that the SRT is more appropriate for subjects with a high level of education rather than a low level of education to differentiate normal cognitive aging from MCI or AD.     

Practice Effects on Motor Control in Healthy Seniors and Patients with Mild Cognitive Impairment and Alzheimer's Disease

ABSTRACT

This research was designed to test the hypothesis that motor practice can enhance the capabilities of motor control in healthy controls (NC) and patients with a diagnosis of probable Alzheimer's disease (AD) and mild cognitive impairment (MCI), and consequently results in better motor performance. Approximately half of the subjects in the NC (n = 31), AD (n = 28), and MCI (n = 29) either received or did not receive practice on a task of fast and accurate arm movement with a digitizer. Changes in movement time (MT), movement smoothness (jerk), and percentage of primary submovement (PPS) were recorded and compared among the three groups across six blocks of trials (baseline and five training sessions). For all subjects, practice improved motor functions as reflected by faster and smoother motor execution, as well as a greater proportion of programming control. Compared to unaffected matched controls, AD and MCI subjects exhibited a greater reduction in movement jerk due to practice. Movement time and PPS data revealed that motor practice appeared to reduce the use of “on-line” correction adopted by the AD or MCI patients while performing the aiming movements. Evidently, their arm movements were quicker, smoother, and temporally more consistent than their untrained peers. The findings of this study shed light on how MCI and AD may affect motor control mechanisms, and suggest possible therapeutic interventions aimed at improving motor functioning in these impaired individuals.     

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 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.     

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.     

The semantic category effect increases with worsening anomia in Alzheimer's type dementia

A large number of patients (n=72) with probable Alzheimer's type dementia (DAT) and mild cognitive impairment (MCI) carried out a picture naming task which comprised stimuli from biological and nonbiological categories. The results were stratified into five ranges of overall naming ability. Every group except those with scores within the range of elderly normal individuals demonstrated better nonbiological naming than biological naming, an effect which increased with worsening impairment. In general, patients diagnosed with other dementia (n=15) did not fit well within the pattern of the DAT/MCI participants, except those known to have a significant semantic impairment. A category effect favoring nonbiological items appears to be robust and produce a predictable pattern across progressive levels of impairment in AD.     

Recollection and Familiarity in Aging Individuals with Mild Cognitive Impairment and Alzheimer’s Disease: A Literature Review

Memory impairment is a central cognitive symptom in mild cognitive impairment (MCI) and Alzheimer Disease (AD). Recognition tasks are often used to characterize and define the nature of memory deficits. Dual-process theories posit that familiarity and recollection are independently involved in the recognition of previously encountered material and both contribute to successful recognition. Recent evidence indicates that there is a double dissociation in the neuronal substrates of those two processes. More precisely, it has been suggested that perirhinal and entorhinal areas are selectively involved in familiarity-based recognition, while the hippocampus is associated with recollection. Interestingly, these regions are among the first to be targeted by neurofibrillary tangles, one of AD’s neuropathological hallmarks. Impairment in recognition performance can occur in the very early stages of AD, such as MCI. To define the nature of recognition impairment in these clinical populations, we reviewed the current literature on familiarity and recollection performance in individuals with MCI and AD. Together with clinical features, methodological factors are taken into consideration in the interpretation of findings.     

Minimal functional brain differences between older adults with and without mild cognitive impairment during the stroop

This investigation compared the neural correlates of inhibition in normal older adults (OAs) and OAs with mild cognitive impairment (MCI). It was hypothesized the MCI group would require a greater amount of resources for inhibition, and therefore display greater functional activation in specific regions of interest (ROIs). Twenty-six OAs without and 17 with MCI completed the Stroop task during functional neuroimaging, and completed additional out-of-scanner neuropsychological measures. During inhibition, there were minimal functional Magnetic Resonance Imaging (fMRI) differences found between groups in a priori specified ROIs and with post-hoc multiple regression analyses. However, these minimal differences did not survive corrected thresholds. Robust differences were found with several tasks of a neuropsychological screening battery. The results of this study suggest only very minimal group differences in fMRI activation during inhibition which may not reliably identify MCI, and this condition may be best detected by traditional neuropsychological techniques.     

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.     

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.     

Neuropsychological Measures that Predict Progression from Mild Cognitive Impairment to Alzheimer's type dementia in Older Adults: a Systematic Review and Meta-Analysis

This study aimed to determine the extent to which cognitive measures can predict progression from mild cognitive impairment (MCI) to Alzheimer’s type dementia (AD), assess the predictive accuracy of different cognitive domain categories, and determine whether accuracy varies as a function of age and length of follow-up. We systematically reviewed and meta-analyzed data from longitudinal studies reporting sensitivity and specificity values for neuropsychological tests to identify individuals with MCI who will develop AD. We searched articles in Medline, Cochrane, EMBASE, PsycINFO, and the Web of Science. Methodological quality was assessed using the STARDem and QUADAS standards. Twenty-eight studies met the eligibility criteria (2365 participants) and reported predictive values from 61 neuropsychological tests with a 31-month mean follow-up. Values were pooled to provide combined accuracy for 14 cognitive domains. Many domains showed very good predictive accuracy with high sensitivity and specificity values (≥ 0.7). Verbal memory measures and many language tests yielded very high predictive accuracy. Other domains (e.g., executive functions, visual memory) showed better specificity than sensitivity. Predictive accuracy was highest when combining memory measures with a small set of other domains or when relying on broad cognitive batteries. Cognitive tests are excellent at predicting MCI individuals who will progress to dementia and should be a critical component of any toolkit intended to identify AD at the pre-dementia stage. Some tasks are remarkable as early indicators, whereas others might be used to suggest imminent progression.     

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.     

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。     

Performance of an Adapted Version of the Timed Up-and-Go Test in People with Cognitive Impairments

In clinical practice, older people with cognitive impairment may have difficulties to understand the instructions of the Timed Up-and-Go (TUGT) test and present a bad performance. The purpose of this study was to identify differences in the TUGT performance, in an adapted version, between older adults with preserved cognition (PC), mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to identify the association between the adapted TUGT performance and cognition among groups. A cross-sectional study was conducted with 118 community-dwelling older adults divided in three groups: PC (n?=?40), MCI (n?=?40) and AD (n?=?38). The evaluation was composed by the adapted TUGT and cognitive assessment (Addenbrooke's Cognitive Examination and Frontal Assessment Battery). Only the cadence of TUGT presented significant difference between groups, specifically between AD versus MCI and PC groups. The main correlations were found between time of TUGT with fluency domain and global cognitive function, especially in the AD Group. The findings contribute to the understanding of how cognition interferes on functional mobility in older people with MCI and AD. The adapted TUGT is easy to perform in clinical practice and can be useful when assessing mobility in people with cognitive impairment.     

Influence of mild cognitive impairment on visual word recognition

The present study examined the effects of normal aging and mild cognitive impairment (MCI) on visual word recognition. Madden et al. (1999) reported evidence of general slowing of cognitive processes in Alzheimer's disease (AD) patients relative to younger adults and healthy older adults using a lexical decision task. It was of interest to determine whether similar effects would be observed in MCI patients relative to healthy younger and older adults. We extended the lexical decision task paradigm developed by Allen et al. (2004b) on younger adults to an examination of the effect(s) of MCI on visual word recognition. Results from the present study showed that healthy older adults and MCI patients performed similarly. That is, both groups took longer than younger adults to process words presented in mixed-case than in consistent-case letters. Mild cognitive impairment patients, however, responded significantly more slowly than healthy older adults across all lexical decision task conditions and showed a trend toward larger case-mixing effects than healthy older adults, which suggests that MCI may result in poorer analytic processing ability. Based on the current findings, evidence of a generalized slowing of cognitive processes using a standard lexical decision task can be expanded to include not only AD patients, but also the preclinical stages of the disease as well.     

Beta-Amyloid Deposition and the Aging Brain

A central issue in cognitive neuroscience of aging research is pinpointing precise neural mechanisms that determine cognitive outcome in late adulthood as well as identifying early markers of less successful cognitive aging. One promising biomarker is beta amyloid (Aβ) deposition. Several new radiotracers have been developed that bind to fibrillar Aβ providing sensitive estimates of amyloid deposition in various brain regions. Aβ imaging has been primarily used to study patients with Alzheimer’s Disease (AD) and individuals with Mild Cognitive Impairment (MCI); however, there is now building data on Aβ deposition in healthy controls that suggest at least 20% and perhaps as much as a third of healthy older adults show significant deposition. Considerable evidence suggests amyloid deposition precedes declines in cognition and may be the initiator in a cascade of events that indirectly leads to age-related cognitive decline. We review studies of Aβ deposition imaging in AD, MCI, and normal adults, its cognitive consequences, and the role of genetic risk and cognitive reserve.     

Correlation between functional mobility and cognitive performance in older adults with cognitive impairment

Association between cognitive impairment and gait performance occurs in mild cognitive impairment (MCI) and Alzheimer‘s disease (AD), particularly under “divided attention” conditions, leading to a greater risk of falls. We studied 36 controls, 42 MCI, and 26 mild AD patients, using the Timed Up-and-Go test (TUG) under four conditions: TUG single – TUG1; TUG cognitive – TUG2; TUG manual –TUG3; TUG cognitive and manual – TUG4. Cognition was assessed using the MMSE, SKT, Exit25, and TMT (A and B). We found significant correlations between cognitive scores and TUG2 [r values (MMSE: –0.383, TMT-A: 0.430, TMT-B: 0.386, Exit25: 0.455, SKT: 0.563)] and TUG4 [(MMSE: –0.398, TMT-A: 0.384, TMT-B: 0.352,Exit25: 0.466, SKT: 0.525)] in the AD group, and between all TUG modalities and SKT in MCI and AD. Our results revealed that functional mobility impairment in cognitive dual tasks correlated to cognitive decline in AD patients and to attention and memory impairment in MCI.