Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: 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). METHODS: 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. RESULT: 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. CONCLUSIONS: 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.     

Abnormal spatial and non-spatial cueing effects in mild cognitive impairment and Alzheimer’s disease

Our aim was to further characterize the clinical concept of mild cognitive impairment (MCI). We examined visual attention-related processing in 12 patients with amnestic MCI, 16 healthy older adults and 16 patients with Alzheimer’s disease (AD) by measuring performance on computer-based tests of attentional disengagement, alerting ability, and inhibition of return. Unlike the healthy older controls, the patients with AD and the patients with amnestic MCI exhibited a significant detriment in both the ability to disengage attention from an incorrectly cued location and the ability to use a visual cue to produce an alerting effect. The pattern of results displayed by the MCI group indicates that patients who only appear clinically to suffer from a deficit in memory also display a deficit in specific aspects of visual attention-related processing, which closely resemble the magnitude seen in AD.     

Abnormal spatial and non-spatial cueing effects in mild cognitive impairment and Alzheimer's disease

Our aim was to further characterize the clinical concept of mild cognitive impairment (MCI). We examined visual attention-related processing in 12 patients with amnestic MCI, 16 healthy older adults and 16 patients with Alzheimer's disease (AD) by measuring performance on computer-based tests of attentional disengagement, alerting ability, and inhibition of return. Unlike the healthy older controls, the patients with AD and the patients with amnestic MCI exhibited a significant detriment in both the ability to disengage attention from an incorrectly cued location and the ability to use a visual cue to produce an alerting effect. The pattern of results displayed by the MCI group indicates that patients who only appear clinically to suffer from a deficit in memory also display a deficit in specific aspects of visual attention-related processing, which closely resemble the magnitude seen in AD.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

Abnormal visual search in mild cognitive impairment and Alzheimer's disease

Our aim was to further characterize the clinical concept of mild cognitive impairment (MCI). We examined the status of visual attention-related processing in such patients in relation to healthy older adults and patients with Alzheimer's disease (AD) by measuring performance on a computer-based visual search task. We tested 20 older adult control participants, 13 patients with amnestic mild cognitive impairment and 12 patients with AD. Patients with AD and with MCI exhibited a significant detriment in visual search performance compared to the older adult controls. The deficit in visual search was greater for the patients with AD than the patients with MCI. The pattern of results displayed by the MCI group indicates that patients who appear clinically to suffer only from a deficit in memory also display a deficit in visual attention-related processing, which although not as severe as those with AD, represents a significant detriment in such performance compared to that seen in healthy ageing.     

Abnormal visual search in mild cognitive impairment and Alzheimer’s disease

Our aim was to further characterize the clinical concept of mild cognitive impairment (MCI). We examined the status of visual attention-related processing in such patients in relation to healthy older adults and patients with Alzheimer’s disease (AD) by measuring performance on a computer-based visual search task. We tested 20 older adult control participants, 13 patients with amnestic mild cognitive impairment and 12 patients with AD. Patients with AD and with MCI exhibited a significant detriment in visual search performance compared to the older adult controls. The deficit in visual search was greater for the patients with AD than the patients with MCI. The pattern of results displayed by the MCI group indicates that patients who appear clinically to suffer only from a deficit in memory also display a deficit in visual attention-related processing, which although not as severe as those with AD, represents a significant detriment in such performance compared to that seen in healthy ageing.     

Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging.

OBJECTIVE: Individuals with mild cognitive impairment (MCI) typically demonstrate memory loss that falls between normal aging (NA) and Alzheimer disease (AD), but little is known about the pattern of memory dysfunction in MCI. METHOD: To explore this issue, California Verbal Learning Test (CVLT) performance was examined across groups of MCI, AD, and NA. RESULTS: MCI subjects displayed a pattern of deficits closely resembling that of AD, characterized by reduced learning, rapid forgetting, increased recency recall, elevated intrusion errors, and poor recognition discriminability with increased false-positives. MCI performance was significantly worse than that of controls and better than that of AD patients across memory indices. Although qualitative analysis of CVLT profiles may be useful in individual cases, discriminant function analysis revealed that delayed recall and total learning were the best aspects of learning/memory on the CVLT in differentiating MCI, AD, and NA. CONCLUSIONS: These findings support the position that amnestic MCI represents an early point of decline on the continuum of AD that is different from normal aging.     

Development of a Psychometrically Equivalent Short Form of the Face–Name Associative Memory Exam for use Along the Early Alzheimer’s Disease Trajectory

Neuropsychologists are developing more challenging and specific tests to detect early and subtle changes in cognition related to preclinical Alzheimer’s disease (AD). The 16-item Face–Name Associative Memory Exam (FNAME-16) is a challenging paired associative memory test able to detect subtle memory changes associated with biomarker evidence of preclinical AD. However, as individuals progress along the AD trajectory, measures that are sensitive at the preclinical stage may become too challenging by the stage of Mild Cognitive Impairment (MCI). Our goal was to develop a modified version of the face–name and face–occupation paired associative memory task (FNAME-12) with fewer stimuli and additional learning trials suitable for use in MCI. We administered the FNAME-12A, an alternate version FNAME 12B, the original FNAME-16, and a series of other neuropsychological measures to 65 clinically normal (CN) older adults (aged 65 to 85) and a subsample characterized by MCI (n = 18). The FNAME-12 exhibited psychometric equivalence with the FNAME-16 (r = .77, p < .001) and was correlated with other measures of episodic and semantic memory. The alternate form, FNAME-12B, was highly correlated with FNAME-12A (r = .76, p < .001). Mean performance on the FNAME 12A, stratified by education, was generated. The task could be completed by our MCI group yet remained challenging in the CN group, providing evidence for its utility along the AD trajectory.     

The Goteborg MCI study: mild cognitive impairment is a heterogeneous condition

BACKGROUND: Mild cognitive impairment (MCI) has been considered a transitional state between normal aging and dementia, characterised by memory impairment but normal general cognitive functioning. Recently other cognitive deficits have been reported. This has led to a modification of MCI criteria. OBJECTIVE: To examine which neuropsychological tests most clearly distinguish MCI subjects from normal controls. METHODS: 112 consecutive MCI subjects and 35 controls were included in the study. The diagnosis of MCI was based on an objective history of cognitive decline and a neuropsychiatric examination, comprising instruments STEP, I-Flex, MMSE, and CDR. Participants were examined with 21 neuropsychological tests in the cognitive domains speed/attention, memory and learning, visuospatial function, language, and executive function. RESULTS: Controls were significantly older. No differences were found in education or general intellectual capacity. Controls performed significantly better than MCI on tests within all five cognitive domains. The clearest differences were seen on language tests, followed by executive function, and learning and memory. Only two subjects (1.8%) were purely amnestic; 17% showed no impairment compared with controls, with a cut off of 1.5 SD below age mean. These subjects were better educated and performed significantly better on measures of general cognitive capacity. CONCLUSIONS: The results illustrate the heterogeneity of MCI, with a significant degree of impairment in all five cognitive domains. When examined with a comprehensive neuropsychological battery, very few subjects had an isolated memory impairment.     

High rate of conversion to Alzheimer's disease in a cohort of amnestic MCI patients

BACKGROUND: A large proportion of patients with amnestic mild cognitive impairment (MCI) progress to Alzheimer's disease (AD), but the rate of conversion is highly variable, depending on selection and inclusion criteria. In the present prospective study, amnestic MCI criteria were applied in order to enrich the study population with prodromal AD patients. METHODS: A composite CERAD word list learning z-score of -1 was applied as a cut-off for memory performance at baseline. Competing causes of memory impairment other than prodromal AD were actively excluded. A cohort of 88 amnestic MCI patients was included; 75 were available for follow-up. RESULTS: After a mean delay of 19 months, 44% were found to have converted to AD, corresponding to an annualized conversion rate of 28%. The rate of new diagnoses other than stable MCI or AD was 6%. Baseline neuropsychological variables were not instrumental to predict progression. CONCLUSION: Amnestic MCI patients, as identified by the present set of criteria, carry a high risk of median-term progression to AD.     

Short-term practice effects in amnestic mild cognitive impairment: implications for diagnosis and treatment

ABSTRACTBackground: Practice effects have been widely reported in healthy older adults, but these improvements due to repeat exposure to test materials have been more equivocal in individuals with mild cognitive impairment (MCI).Methods: The current study examined short-term practice effects in MCI by repeating a brief battery of cognitive tests across one week in 59 older adults with amnestic MCI and 62 intact older adults.Results: Participants with amnestic MCI showed significantly greater improvements on two delayed recall measures (p < 0.01) compared to intact peers. All other practice effects were comparable between these two groups. Practice effects significantly improved scores in the MCI group so that 49% of them were reclassified as "intact" after one week, whereas the other 51% remained "stable" as MCI. Secondary analyses indicated the MCI-Intact group demonstrated larger practice effects on two memory measures than their peers (p < 0.01).Conclusions: These results continue to inform us about the nature of memory deficits in MCI, and could have implications for the diagnosis and possible treatment of this amnestic condition.     

The Semantic Object Retrieval Test (SORT) in amnestic mild cognitive impairment.

BACKGROUND: Between 10% and 15% of patients with the amnestic variety of Mild Cognitive Impairment (MCI) convert to Alzheimer disease (AD) per year. OBJECTIVE: Characterize cognitive markers that may herald conversion from MCI to AD and directly assess semantic memory in patients meeting criteria for amnestic MCI. DESIGN: Thirty-five amnestic MCI patients and 121 healthy aging controls enrolled at an Alzheimer Disease Center received a battery of standard neuropsychologic tests, and the Semantic Object Retrieval Test (SORT), a test that we have developed for the assessment of semantic memory and subsequent name production, and that has been shown to be able to differentiate between normals and patients with AD. RESULTS: On the basis of normative data from the SORT, the MCI subjects could be divided into 2 groups: 10 patients (29%) with a significant semantic impairment (SI+) and 25 without a semantic memory deficit (SI-). There was a significant correlation between all SORT variables and performance on the Boston Naming Test. In this MCI population, significantly impaired SORT performance was associated with a relative decrease in performance on tests of frontal lobe functions, although disruption of thalamic-related processes cannot be excluded as an etiology for semantic memory impairment. CONCLUSIONS: The SORT is a specific test of semantic memory, and is a sensitive measure of semantic memory deficits in patients who otherwise meet criteria for amnestic MCI. Using this specific assessment tool, a significant number of MCI patients were found to have semantic memory deficits. As these patients may be early in the course of possible progression toward dementia, the SORT or other tests of semantic memory may provide important diagnostic or prognostic information in patients with MCI.     

Visual mismatch negativity highlights abnormal pre-attentive visual processing in mild cognitive impairment and Alzheimer's disease

Alzheimer's disease (AD) and mild cognitive impairment (MCI) are traditionally characterised in relation to abnormalities in higher-level brain function, particularly memory. However, in the study presented here we report significant abnormality in pre-attentive visual processing in both MCI and AD compared to healthy ageing. The functional integrity of the automatic change detection system was determined by measuring the visual mismatch negativity (vMMN) component of the N2 visual event-related potential (ERP) in 8 individuals with amnestic MCI, 10 individuals with AD and 10 healthy older adult controls. Compared to healthy ageing, both the MCI and AD groups displayed a significant abnormally increased vMMN over the 140–250 ms measurement epoch although such effects were not apparent over the later 250–400 ms epoch. These novel findings support the view that deficits in brain function in both AD and MCI are not exclusively high-level and indeed that abnormal output from ‘low level’ or pre-attentive processes (as evinced by the abnormal vMMN) is likely to contribute to the high-level processing deficits so characteristic of these clinical disorders.     

Brain substrates of learning and retention in mild cognitive impairment diagnosis and progression to Alzheimer's disease

Understanding the underlying qualitative features of memory deficits in mild cognitive impairment (MCI) can provide critical information for early detection of Alzheimer's disease (AD). This study sought to investigate the utility of both learning and retention measures in (a) the diagnosis of MCI, (b) predicting progression to AD, and (c) examining their underlying brain morphometric correlates. A total of 607 participants were assigned to three MCI groups (high learning-low retention; low learning-high retention; low learning-low retention) and one control group (high learning-high retention) based on scores above or below a 1.5 SD cutoff on learning and retention indices of the Rey Auditory Verbal Learning Test. Our results demonstrated that MCI individuals with predominantly a learning deficit showed a widespread pattern of gray matter loss at baseline, whereas individuals with a retention deficit showed more focal gray matter loss. Moreover, either learning or retention measures provided good predictive value for longitudinal clinical outcome over two years, although impaired learning had modestly better predictive power than impaired retention. As expected, impairments in both measures provided the best predictive power. Thus, the conventional practice of relying solely on the use of delayed recall or retention measures in studies of amnestic MCI misses an important subset of older adults at risk of developing AD. Overall, our results highlight the importance of including learning measures in addition to retention measures when making a diagnosis of MCI and for predicting clinical outcome.     

Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment

CONTEXT: The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established. OBJECTIVES: To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion. DESIGN: Patients were followed up semiannually and controls annually. Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures. SETTING: Memory disorders clinic. PARTICIPANTS: One hundred forty-eight patients reporting memory problems and 63 group-matched controls. MAIN OUTCOME MEASURE: A consensus diagnosis of probable AD. RESULTS: At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 +/- 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%. CONCLUSIONS: Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.     

Longitudinal change in neuropsychological performance using latent growth models: a study of mild cognitive impairment

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.     

Memory for the September 11, 2001, terrorist attacks one year later in patients with Alzheimer's disease, patients with mild cognitive impairment, and healthy older adults

Although there are many opportunities to study memory in patients with Alzheimer's disease (AD) in the laboratory, there are few opportunities to study memory for real world events in these patients. The September 11, 2001 terrorist attacks provided one such opportunity. Patients with AD, patients with mild cognitive impairment (MCI), and healthy older adults were given a telephone questionnaire in the initial weeks after the event, again three to four months later, and finally one year afterwards to evaluate their memory for the September 11, 2001 terrorist attacks. We were particularly interested in using the attacks as an opportunity to examine the decline of episodic memory in patients with AD, patients with MCI, and older adult controls over a period of months. We found that compared to healthy older adults, patients with AD and MCI showed impaired memory at the initial time point, more rapid forgetting from the initial to the three-month time point, and very similar changes in memory from the three-month to the one-year time point. We speculated that these findings were consistent with patients with AD and MCI showing initial impaired encoding and a more rapid rate of forgetting compared with healthy older adults, but that once the memories had been consolidated, their decay rate became similar to that of healthy older adults. Lastly, although memory distortions were common among all groups, they were greatest in the patients with AD.     

Category fluency in mild cognitive impairment: reduced effect of practice in test-retest conditions

Verbal fluency tests are commonly used in neurocognitive and mental status examinations in patients with suspected dementia. Inflation of test scores as a result of practice effects may yield false-negative results in test-retest and multidisciplinary settings, particularly among patients with mild cognitive deficits. To address this issue, animal naming was administered twice within a 1-week period to a group of individuals referred for suspected dementia who were ultimately diagnosed with mild cognitive impairment (MCI; amnestic form), probable Alzheimer disease (AD), or no dementia. A 2 x 3 repeated-measures analysis of variance revealed a statistically significant interaction between administration time and group. Post hoc analyses indicated that nondemented controls were the only group to demonstrate a significant practice effect, producing an average of approximately three more animal names at time two. Like patients with a diagnosis of AD, subjects with amnestic MCI failed to benefit from repeated exposure to the animal naming test, and only controls showed an average improvement upon retest. This underscores the cognitive similarity between individuals diagnosed with amnestic MCI and AD and suggests that improvement upon retest may be a diagnostically useful finding.     

Yes/No Versus Forced-Choice Recognition Memory in Mild Cognitive Impairment and Alzheimer's Disease: Patterns of Impairment and Associations with Dementia Severity

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.