Memory tests are sensitive to early identification of Alzheimer’s disease (AD) but less useful as the disease advances. However, assessing particular types of recognition memory may better characterize dementia severity in later stages of AD. We sought to examine patterns of recognition memory deficits in individuals with AD and mild cognitive impairment (MCI). Memory performance and global cognition data were collected from participants with AD (n=37), MCI (n=37), and cognitively intact older adults (normal controls, NC; n=35). One-way analyses of variance (ANOVAs) examined differences between groups on yes/no and forced-choice recognition measures. Individuals with amnestic MCI performed worse than NC and nonamnestic MCI participants on yes/no recognition, but were comparable on forced-choice recognition. AD patients were more impaired across yes/no and forced-choice recognition tasks. Individuals with mild AD (≥120 Dementia Rating Scale, DRS) performed better than those with moderate-to-severe AD (<120 DRS) on forced-choice recognition, but were equally impaired on yes/no recognition. There were differences in the relationships between learning, recall, and recognition performance across groups. Although yes/no recognition testing may be sensitive to MCI, forced-choice procedures may provide utility in assessing severity of anterograde amnesia in later stages of AD. Implications for assessment of insufficient effort and malingering are also discussed.
Recognition memory; Alzheimer’s disease; Mild cognitive impairment; Dementia severity; Neuropsychology
We compared indices of the revised version of the Wechsler Memory Scale (WMS-R) and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and 25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone.
Alzheimer's disease; Attention deficit; Delayed recall; Executive function; Recent memory; Three-dimensional stereotactic surface projections; Voxel-based specific region analysis; Working memory
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has demonstrated adequate sensitivity in detecting cognitive impairment in a number of neuropsychiatric conditions, including Alzheimer's disease. However, its ability to detect milder cognitive deficits in the elderly has not been examined. The current study examined the clinical utility of the RBANS by comparing two groups: Patients with Mild Cognitive Impairment (MCI; n = 72) and cognitively intact peers (n = 71). Significant differences were observed on the RBANS Total score, 3 of the 5 Indexes, and 6 of the 12 subtests, with individuals with MCI performing worse than the comparison participants. Specificity was very good, but sensitivity ranged from poor to moderate. Areas under the receiver operating characteristic curves for the RBANS Immediate and Delayed Memory Indexes and the Total Scale score were adequate. Although significant differences were observed between groups and the areas under the curves were adequate, the lower sensitivity values of the RBANS suggests that caution should be used when diagnosing conditions such as MCI.
Mild Cognitive Impairment; Diagnostic accuracy; Repeatable Battery for the Assessment of Neuropsychological Status
Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fuster's (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI.
Mild cognitive impairment; Single domain mild cognitive impairment; Multiple domain mild cognitive impairment; Alzheimer's disease; The Titanic Effect; Executive control
Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI.
Mild cognitive impairment; MCI; Declarative memory; Executive control; Philadelphia (repeatable) Verbal Learning Test; P(r)VLT; Cluster analysis; Boston Process Approach
The Mild Cognitive Impairment Screen (MCIS) is a computer-based cognitive assessment designed for clinical and research use in detecting amnestic mild cognitive impairment (aMCI). Performance on the MCIS is reported as the Memory Performance Index (MPI). However, the comparability between the MPI and traditional neuropsychological tests in detecting aMCI, and in differentiating it from Alzheimer’s disease (AD) and normal aging has not been examined. A cross-sectional study was conducted to assess the validity of the MPI relative to standard neuropsychological measures. Participants included 12 individuals diagnosed with aMCI, 49 with mild AD, and 25 healthy elderly. The MCIS significantly discriminated among aMCI, AD, and healthy elderly controls. The MCIS is effective in detecting aMCI, and in discriminating it from cognitive changes observed in AD and normal aging. The MCIS may be a valuable tool in the identification of elderly at high risk for dementia due to its ease-of-use and brief administration time.
Mild Cognitive Impairment; Dementia; Alzheimer’s Disease; Screening; Memory
To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study.
MCI was classified as MCI‐amnestic type (MCI‐AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI‐multiple cognitive deficits type (MCI‐MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition.
MCI‐AT (n = 10) had worse verbal and non‐verbal memory performance than MCI‐MCDT (n = 28) or normal controls (n = 374). By contrast, MCI‐MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI‐AT or normal controls. MCI‐MCDT subjects had memory deficits, though they were less pronounced than in MCI‐AT. Of the MCI‐MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI‐MCDT with memory disorders had more language deficits than MCI‐MCDT without memory disorders. By contrast, MCI‐MCDT without memory deficits had more fine motor control deficits than MCI‐MCDT with memory deficits.
The most frequent form of MCI was the MCI‐MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI‐MCDT cases did not have memory impairment. Study of idiopathic amnestic and non‐amnestic forms of MCI is essential for an understanding of the aetiology of MCI.
Alzheimer's disease; aging; dementia; mild cognitive impairment; neuropsychology
Although memory deficits are typically the earliest and most profound symptoms of Alzheimer's disease (AD) and mild cognitive impairment (MCI), there is increasing recognition of subtle executive dysfunctions in these patients. The purpose of the present study was to determine the sensitivity of the Behavioral Assessment of the Dysexecutive Syndrome (BADS), and to detect early specific signs of the dysexecutive syndrome in the transition from normal cognition to dementia. The BADS was administered to 50 MCI subjects, 50 mild AD patients, and 50 normal controls. Statistically significant differences were found among the three groups with the AD patients performing most poorly, and the MCI subjects performing between controls and AD patients. The Rule Shift Cards and the Action Program subtests were the most highly discriminative between MCI and controls; the Zoo Map and Modified Six Elements between MCI and AD; and the Action Program, Zoo Map, and Modified Six Elements between AD and controls. These results demonstrate that the BADS is clinically useful in discriminating between normal cognition and progressive neurodegenerative conditions. Furthermore, these data confirm the presence of a dysexecutive syndrome even in mildly impaired elderly subjects.
The Behavioural Assessment of the Dysexecutive Syndrome; Zoo Map Test; Cognition; Dementia; Aging; Neuropsychology
In this study we sought to differentiate participants with amnestic mild cognitive impairment (a-MCI) from those with mild dementia of Alzheimer’s type (m-DAT) and normal controls by modifying an existing test of spatial context memory (SCMT) designed so as to evaluate the function of brain regions affected in early m-DAT. We found that participants with a-MCI had better total scores on our modified SCMT than those with m-DAT. Furthermore, the locational memory subtest was able to discriminate between those with a-MCI and m-DAT. Additionally, compared with other screening tests, our spatial context memory test showed high sensitivity and specificity in discerning those with a-MCI from the normal population but, was relatively ineffective in discriminating a-MCI patients from those with m-DAT. We conclude that our modified test of SCMT is an effective tool for discriminating a-MCI from m-DAT and does so by detecting differences in locational memory.
Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD.
The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD.
As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.
Cognitively intact older individuals at risk for developing Alzheimer's disease frequently show increased functional magnetic resonance imaging (fMRI) brain activation presumably associated with compensatory recruitment, whereas mild cognitive impairment (MCI) patients tend not to show increased activation presumably due to reduced neural reserve. Previous studies, however, have typically used episodic memory activation tasks, placing MCI participants at a performance disadvantage relative to healthy elders. In this event-related fMRI study, we employed a low effort, high accuracy semantic memory task to determine if increased activation of memory circuits is preserved in amnestic MCI when task performance is controlled. Fifty-seven participants, aged 65–85 years, comprised three groups (n = 19 each): amnestic MCI patients; cognitively intact older participants at risk for developing Alzheimer's disease based on having at least one ApoE ε4 allele and a positive family history of Alzheimer's disease (At Risk); and cognitively intact participants without Alzheimer's disease risk factors (Control). fMRI was conducted on a 3T MR scanner while participants performed a famous name discrimination task. Participants also underwent neuropsychological testing outside the scanner; whole brain and hippocampal atrophy were assessed from anatomical MRI scans. The three groups did not differ on demographic variables or on fame discrimination performance (>87% correct for all groups). As expected, the amnestic MCI participants demonstrated reduced episodic memory performance. Spatial extent of activation (Fame—Unfamiliar subtraction) differentiated the three groups (Control = 0 ml, At Risk = 9.7 ml, MCI = 34.7 ml). The MCI and At Risk groups showed significantly greater per cent signal change than Control participants in 8 of 14 functionally defined regions, including the medial temporal lobe, temporoparietal junction, and posterior cingulate/precuneus. MCI participants also showed greater activation than Controls in two frontal regions. At Risk, but not MCI, participants showed increased activity in the left hippocampal complex; MCI participants, however, evidenced increased activity in this region when hippocampal atrophy was controlled. When performance is equated, MCI patients demonstrate functional compensation in brain regions subserving semantic memory systems that generally equals or exceeds that observed in cognitively intact individuals at risk for Alzheimer's disease. This hyperactivation profile in MCI is even observed in the left hippocampal complex, but only when the extent of hippocampal atrophy is taken into consideration.
Area under the curve (AUC); fMRI; semantic memory; mild cognitive impairment; APOE ε4
Person identification represents a unique category of semantic knowledge that is commonly impaired in Alzheimer's Disease (AD), but has received relatively little investigation in patients with Mild Cognitive Impairment (MCI). The current study examined the retrieval of semantic knowledge for famous names from three time epochs (recent, remote, and enduring) in two participant groups; 23 aMCI patients and 23 healthy elderly controls. The aMCI group was less accurate and produced less semantic knowledge than controls for famous names. Names from the enduring period were recognized faster than both recent and remote names in both groups, and remote names were recognized more quickly than recent names. Episodic memory performance was correlated with greater semantic knowledge particularly for recent names. We suggest that the anterograde memory deficits in the aMCI group interferes with learning of recent famous names and as a result produces difficulties with updating and integrating new semantic information with previously stored information. The implications of these findings for characterizing semantic memory deficits in MCI are discussed.
semantic memory; aging; fame recognition; person identity; remote memory; temporal gradient
The preclinical Alzheimer's disease (AD) - amnestic mild cognitive impairment (MCI) - is manifested by phenotypes classified into exclusively memory (single-domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and lingual gyri). A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination.
Exhaustive neuropsychological assessment of mild cognitive impairment (MCI) subjects frequently identifies cognitive deficits other than memory. However, visuoperception has rarely been investigated in MCI. The 15-Objects Test (15-OT), a visual discrimination task based on the Poppelreuter Test, consists of 15 overlapping objects. Poppelreuter-type tests are frequently used to detect visual agnosia. However, more complex tests, such as the 15-OT, are required to detect visuoperceptual signs in those patients who perform correctly on simple tests. The aim of the present study was to investigate visuoperceptual deficits in MCI patients and to assess the usefulness of the 15-OT to discriminate Alzheimer’s disease (AD) and MCI patients from controls. The 15-OT, and a neuropsychological battery included in the diagnostic assessment, was administered to 44 healthy controls, 44 MCI patients, and 44 mild AD patients. Performance on the 15-OT was significantly different between groups. MCI scored between AD and controls. When MCI and AD patients had relatively normal performance on simple tests (Poppelreuter), increased significant abnormalities were found by a more difficult visuoperceptual test (15-OT). Regression analyses showed that the 15-OT was a significant predictor of group membership, but the Poppelreuter Test did not significantly contribute to the models. Visuoperceptual processing is impaired early in the clinical course of AD. The 15-OT allows detection of visuoperceptual deficits in the preclinical and mild AD stages, when classical tests are still unable to detect subtle deficits. So, its inclusion in neuropsychological batteries that are nowadays used in the clinical practice would allow increasing their diagnostic potential.
Visual discrimination; Visuoperceptual; Mild cognitive impairment; Alzheimer’s disease
The goal of the current study was to examine cognitive change in both healthy controls (n=229) and individuals with mild cognitive impairment (MCI) (n=397) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We applied latent growth modeling to examine baseline and longitudinal change over 36 months in five cognitive factors derived from the ADNI neuropsychological test battery (memory, executive function/processing speed, language, attention and visuospatial). At baseline, MCI patients demonstrated lower performance on all of the five cognitive factors when compared to controls. Both controls and MCI patients declined on memory over 36 months; however, the MCI patients declined at a significantly faster rate than controls. The MCI patients also declined over 36 months on the remaining four cognitive factors. In contrast, the controls did not exhibit significant change over 36 months on the non-memory cognitive factors. Within the MCI group, executive function declined faster than memory, while the other factor scores changed slower than memory over time. These findings suggest different patterns of cognitive change in healthy older adults and MCI patients. The findings also suggest that, when compared with memory, executive function declines faster than other cognitive factors in patients with MCI. Thus, decline in non-memory domains may be an important feature for distinguishing healthy older adults and persons with MCI.
ADNI; Neuropsychology; Cognition; Mild cognitive impairment; Cognitive change; Executive function
This study aims to investigate the relationship between executive function and verbal memory and to explore the underlying neuroanatomical correlates in 358 individuals with amnestic mild cognitive impairment (MCI) and 222 healthy controls (HCs). The MCI participants were divided into 2 groups (high vs. low) based on executive function task performance. Results demonstrated that although both MCI groups were impaired on all memory measures relative to HCs, MCI individuals with higher executive function (HEF) demonstrated better verbal memory performance than those with lower executive function (LEF), particularly on measures of learning. The 2 MCI groups did not differ in mesial temporal morphometric measures, but the MCI LEF group showed significant thinning in dorsolateral prefrontal and posterior cingulate cortices bilaterally compared with the MCI HEF and HCs. Further, thickness in numerous regions of frontal cortex, and bilateral posterior cingulate, was significantly associated with memory performance in all MCI participants above and beyond the contribution of the mesial temporal regions known to be associated with episodic memory. Overall, these results demonstrate the importance of evaluating executive function in individuals with MCI to predict involvement of brain areas beyond the mesial temporal lobe.
Alzheimer's disease; clinical subtypes; cognition; longitudinal outcome; morphometry
To evaluate whether ratings on Clinical Dementia Rating (CDR) items related to instrumental activities of daily living (IADL) are associated with cognitive or brain morphometric characteristics of participants with mild cognitive impairment (MCI) and global CDR scores of 0.5.
Baseline cognitive and morphometric data were analyzed for 283 individuals with MCI who were divided into 2 groups (impaired and intact) based on their scores on the 3 CDR categories assessing IADL. Rates of progression to Alzheimer disease (AD) over 2 years were also compared in the 2 groups.
The impaired IADL MCI group showed a more widespread pattern of gray matter loss involving frontal and parietal regions, worse episodic memory and executive functions, and a higher percentage of individuals progressing to AD than the relatively intact IADL MCI group.
The results demonstrate the importance of considering functional information captured by the CDR when evaluating individuals with MCI, even though it is not given equal weight in the assignment of the global CDR score. Worse impairment on IADL items was associated with greater involvement of brain regions beyond the mesial temporal lobe. The conventional practice of relying on the global CDR score as currently computed underutilizes valuable IADL information available in the scale, and may delay identification of an important subset of individuals with MCI who are at higher risk of clinical decline.
To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI).
From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests.
In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks.
Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.
Amnestic mild cognitive impairment; Alzheimer's disease; Executive function; Fluency
Alzheimer’s disease (AD) is the most common dementing illness. Development of effective treatments directed at AD requires an early diagnosis. Mild cognitive impairment (MCI) often heralds AD. Thus, characterizing MCI is fundamental to the early diagnosis of AD.
Nineteen MCI patients referred from a memory loss clinic and 27 healthy subjects, all followed for 3 years.
Metabolism scans (MCI minus controls) were compared voxel-wise after anatomical normalization and were examined both visually and with a computerized classifier.
Agreement between raters as to whether the individual scans were normal or abnormal was high. Agreement between raters of the eventual clinical diagnosis and baseline metabolic pattern was poor. A computerized classifier was unsuccessful at classifying MCI from normal; however, its performance improved when using only prototypic AD-like MCI scans, indicating the classifier worked well when shared patterns existed in the data. Outcomes on follow-up were 9/19 AD; 5/19 remained MCI; and 5/19 developed dementias other than AD. Both cases of early Lewy body dementia (LBD) showed an AD-like metabolic pattern.
Visual inspection proved reliable in determining normal from abnormal scans; but it proved unreliable at predicting diagnosis on follow-up. Computerized classification of MCI using an AD-like metabolic template (such as derived from the averaged MCI images) showed potential to identify patients that will develop AD. However, the metabolic pattern in early LBD did not differ from that in AD.
MCI; PET; support vector machine; brain metabolism; diagnosis; Alzheimer; frontotemporal dementia; Lewy body; aging; classification
Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally.
To characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures.
A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials.
The subjects with MCI were more memory impaired than the cognitively normal subjects but not as impaired as the subjects with AD. Nonmemory cognitive measures were only minimally impaired in the subjects with MCI. The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the subjects with MCI were on antidementia therapies. There was minimal movement on the Alzheimer's Disease Assessment Scale–Cognitive Subscale for the normal control subjects, slight movement for the subjects with MCI of 1.1, and a modest change for the subjects with AD of 4.3. Baseline CSF measures of Aβ-42 separated the 3 groups as expected and successfully predicted the 12-month change in cognitive measures.
The Alzheimer's Disease Neuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics. The 12-month progression rate of MCI was as predicted, and the CSF measures heralded progression of clinical measures over 12 months.
= Alzheimer disease;
= Alzheimer's Disease Assessment Scale–Cognitive subscale;
= Alzheimer's Disease Neuroimaging Initiative;
= confidence interval;
= mild cognitive impairment;
= Mini-Mental State Examination.
Despite memory failures being a central feature of Amnestic Mild Cognitive Impairment (a-MCI), there is limited research into the nature of the memory impairment associated with this condition. A further understanding could lead to refinement of criteria needed to qualify for this designation and aid in prediction of who will progress to development of clinical Alzheimer’s disease. Dual process models posit that recognition memory is supported by the dissociable processes of recollection and familiarity. The present study sought to evaluate recognition memory in a-MCI in the framework of the dual process model. Patients with a-MCI and age- and education-matched controls were tested on three memory paradigms. Two paradigms were modifications of the process-dissociation procedure in which recollection required either memory of word-pair associations (associative) or the font color of words at study (featural). A final paradigm utilized the task-dissociation methodology comparing performance for item and visual spatial source memory. All three tasks revealed that familiarity was impaired to at least the same extent as recollection. As familiarity is thought to be spared in normal aging, its measurement may provide a relatively specific marker for the early pathological changes of Alzheimer’s disease.
Alzheimer’s disease; memory; dual process; process-dissociation procedure; task-dissociation
Mild cognitive impairment (MCI) is often a precursor to Alzheimer’s disease. Little research has examined the efficacy of cognitive rehabilitation in patients with MCI, and the relevant neural mechanisms have not been explored. We previously reported on a pilot study showing the behavioral efficacy of cognitive rehabilitation using mnemonic strategies for face-name associations in patients with MCI. Here we used functional magnetic resonance imaging (fMRI) to test whether there were training-specific changes in activation and connectivity within memory-related areas.
Six patients with amnestic, multi-domain MCI underwent pre- and post-training fMRI scans, during which they encoded 90 novel face-name pairs, and completed a 4-choice recognition memory test immediately after scanning. Patients were taught mnemonic strategies for half the face-name pairs during three intervening training sessions.
Training-specific effects comprised significantly increased activation within a widespread cerebral cortical network involving medial frontal, parietal, and occipital regions, the left frontal operculum and angular gyrus, and regions in left lateral temporal cortex. Increased activation common to trained and untrained stimuli was found in a separate network involving inferior frontal, lateral parietal and occipital cortical regions. Effective connectivity analysis using multivariate, correlation-purged Granger causality analysis revealed generally increased connectivity after training, particularly involving the middle temporal gyrus and foci in the occipital cortex and the precuneus.
Our findings suggest that the effectiveness of explicit memory training in patients with MCI is associated with training-specific increases in activation and connectivity in a distributed neural system that includes areas involved in explicit memory.
cognitive rehabilitation; mnemonic strategy; Alzheimer’s disease; aging; functional magnetic resonance imaging (fMRI); Granger causality analysis
Remembering the location of objects in the environment is both important in everyday life and difficult for patients with amnestic mild cognitive impairment (aMCI), a clinical precursor to Alzheimer’s disease. To test the hypothesis that memory impairment for object location in aMCI reflects hippocampal dysfunction, we used an event-related functional magnetic resonance imaging paradigm to compare patients with aMCI and healthy elderly controls (HEC) as they encoded 90 ecologically-relevant object-location associations (OLAs). Two additional OLAs, repeated a total of 45 times, served as control stimuli. Memory for these OLAs was assessed following a 1-hour delay. The groups were well matched on demographics and brain volumetrics. Behaviorally, HEC remembered significantly more OLAs than did aMCI patients. Activity differences were assessed by contrasting activation for successfully encoded novel stimuli vs. repeated stimuli. The HEC demonstrated activity within object-related (ventral visual stream), spatial location-related (dorsal visual stream), and feature binding-related cortical regions (hippocampus and other memory-related regions) as well as in frontal cortex and associated subcortical structures. Activity in most of these regions correlated with memory test performance. Although the aMCI patients demonstrated a similar activation pattern, the HEC showed significantly greater activity within each of these regions. Memory test performance in aMCI patients, in contrast to the HEC, was correlated with activity in regions involved in sensorimotor processing. We conclude that aMCI patients demonstrate widespread cerebral dysfunction, not limited to the hippocampus, and rely on encoding-related mechanisms that differ substantially from healthy individuals.
Learning; memory; associative memory; object-location associations; Alzheimer’s disease; aging; hippocampus; functional magnetic resonance imaging; fMRI
Mild cognitive impairment (MCI) is often associated with the preclinical phase of Alzheimer's disease (AD). Special scoring of word-list recall data for serial position has been suggested to improve discrimination of normal aging from dementia. We examined serial position effects in word-list recall for MCI participants compared to Alzheimer patients and controls. Individuals with MCI, like Alzheimer patients, had a diminished primacy effect in recalling words from a list. No alternative scoring system was better than standard scoring of word list recall in distinguishing MCI patients from controls. Retention weighted scoring improved the discrimination of MCI and AD groups.
Background and Purpose
The objective of this study was to determine the benefits of cognitive training in patients with amnestic mild cognitive impairment (aMCI) and those with early Alzheimer's disease (AD).
Eleven patients with aMCI and nine with early AD (stage 4 on the Global Deterioration Scale) participated in this study. Six participants with aMCI and six with AD were allocated to the cognitive training group, while five participants with aMCI and three with AD were allocated to a wait-list control group. Multicomponent cognitive training was administered in 18 weekly, individual sessions. Outcome measures were undertaken at baseline, and at 2 weeks and 3 months of follow-up.
In the trained MCI group, there were significant improvements in the delayed-recall scores on the Seoul Verbal Learning Test at both the 2-week and 3-month follow-ups compared with baseline (baseline, 1.6±1.5; 2 weeks, 4.4±1.5, p=0.04; 3 months, 4.6±2.3, p=0.04). The phonemic fluency scores (1.0±0.8 vs. 5.0±1.8, p=0.07) and Korean Mini-Mental State Examination scores (18.8±0.5 vs. 23.8±2.2, p=0.07) also showed a tendency toward improvement at the 2-week follow-up compared to baseline in the trained AD group.
This study provides evidence of the effectiveness of cognitive training in aMCI and early AD. The efficacy of cognitive training programs remains to be verified in studies with larger samples and a randomized design.
Alzheimer's disease; cognitive therapy; memory; mild cognitive impairment; training