Subjective memory complaints in Chinese subjects with mild cognitive impairment and early Alzheimer's disease

BACKGROUND: Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia. However, there is inconsistent opinion as to the validity of subjective memory complaints as a criterion for diagnosis. OBJECTIVE: This study aimed to examine the potential significance of applying a short memory questionnaire in the assessment of Chinese subjects with MCI and early dementia. METHODS: Three hundred and six ambulatory Chinese subjects were recruited. Each participant completed a short memory questionnaire. They were also assessed with the Chinese versions of the mini-mental state examination (CMMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), category verbal fluency test (CVFT) and span tests. Severity of cognitive impairment was evaluated using the Clinical Dementia Rating (CDR); subjects with CDR 0.5 were further classified into MCI not demented (MCIND) and MCI possible incipient dementia (MCIID) depending on the subscale scores of CDR. RESULTS: An increasing frequency of memory complaints with increasing CDR was observed (Kruskal Wallis test, chi square = 21.29, df 3, p < 0.001). With a cutoff of 3 or more memory complaints, the memory questionnaire demonstrated a sensitivity of 65.3% and 70.4% in identifying subjects with incipient and early dementia respectively. Significant associations between memory complaints and most cognitive test performance were found (Spearman's correlations, p < 0.01). Logistic regression analysis revealed that educational level, the memory questionnaire, ADAS-Cog total and delayed recall scores were significant predictors of MCIID status. CONCLUSIONS: The findings suggested that a short memory questionnaire is useful in the screening of MCI, particularly in subjects who already present with subtle functioning disturbances. Subjective memory complaints were significant correlated with objective performance of memory functions, reflecting the usefulness of memory complaints in the assessment of MCI.     

Subjective complaints and self-evaluation of memory test performance in Questionable dementia

BACKGROUND: The clinical significance of subjective memory complaints in elderly subjects has been an area of active research. In this study, we evaluated subjective complaints and self-evaluation of memory test performance in subjects with Questionable dementia (QD) and mild Alzheimer's disease (AD). METHODS: Ninety-two subjects (35 cognitively intact normal controls NC, 33 QD, and 24 mild AD) were assessed. Subjective memory complaints were evaluated using a memory inventory for the Chinese (MIC); objective assessment of awareness was assessed by the self-evaluation of own memory test performance. Cognitive function was assessed with the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Category Verbal Fluency Test (CVFT) and Executive Interview (EXIT-25). Depressive symptoms were evaluated with the Cornell Scale for Depression in Dementia (CSDD). RESULTS: The total number of subjective memory complaints (MI-tol) were significantly different between different subject groups (Kruskal Wallis test, chi2 = 13.19, p = 0.001). Significant correlations between scores of the MI-tol and CSDD (r = 0.33, p < 0.001), CMMSE (r = -0.33, p < 0.001), CDR (r = 0.36, p < 0.001) were found. In self-evaluation of memory test performance, the NC group tended to under-estimate while the AD subjects tended to over-estimate their performance. Group differences in the discrepancies of self-evaluation of memory performance were significant for both the immediate (Kruskal Wallis test, chi2 = 9.86, p = 0.007) and delayed recall (Kruskal Wallis test, chi2 = 10.55, p < 0.001) trials. CONCLUSIONS: Subjects with QD and mild AD showed higher frequency of subjective memory complaints, reflecting that the subjects still retain some ability to appreciate own memory function. However, the trend for over-estimation of performance in AD subjects suggests that the precision of estimation may be suboptimal. Moreover, depressive symptoms may affect the presentation of memory complaints and this factor should be carefully considered in future prospective studies.     

The Effect of Cognitive Training in Patients with Mild Cognitive Impairment and Early Alzheimer's Disease: A Preliminary Study

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).

Methods

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.

Results

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.

Conclusions

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.     

Further evidence of preserved memory function in Alzheimer's disease

Memory performance of elderly patients in the early stages of Alzheimer's disease (DAT) was compared with that of elderly control subjects. In explicit tests of recognition memory, which involve conscious recollection, the DAT patients were grossly impaired. In implicit tests of anagram solution and wordstem completion, which do not require conscious recollection, the DAT patients were not impaired. These findings further support the idea that a separate memory system, episodic memory, underlies conscious recollection, that it is this system which is most commonly damaged in amnesia, and that memory systems not involving conscious recollection may be spared in the early stages of Alzheimer's disease.     

Distinct medial temporal contributions to different forms of recognition in amnestic mild cognitive impairment and Alzheimer's disease

The simplest expression of episodic memory is the experience of familiarity, the isolated recognition that something has been encountered previously. Brain structures of the medial temporal lobe (MTL) make essential contributions to episodic memory, but the distinct contributions from each MTL structure to familiarity are debatable. Here we used specialized tests to assess recognition impairments and their relationship to MTL integrity in people with amnestic mild cognitive impairment (aMCI, n=19), people with probable Alzheimer's disease (AD; n=10), and age-matched individuals without any neurological disorder (n=20). Recognition of previously presented silhouette objects was tested in two formats—forced-choice recognition with four concurrent choices (one target and three foils) and yes/no recognition with individually presented targets and foils. Every foil was extremely similar to a corresponding target, such that forced-choice recognition could be based on differential familiarity among the choices, whereas yes/no recognition necessitated additional memory and decision factors. Only yes/no recognition was impaired in the aMCI group, whereas both forced-choice and yes/no recognition were impaired in the AD group. Magnetic resonance imaging showed differential brain atrophy, as MTL volume was reduced in the AD group but not in the aMCI group. Pulsed arterial spin-labeled scans demonstrated that MTL blood flow was abnormally increased in aMCI, which could indicate physiological dysfunction prior to the emergence of significant atrophy. Regression analyses with data from all patients revealed that regional patterns of MTL integrity were differentially related to forced-choice and yes/no recognition. Smaller perirhinal cortex volume was associated with lower forced-choice recognition accuracy, but not with lower yes/no recognition accuracy. Instead, smaller hippocampal volumes were associated with lower yes/no recognition accuracy. In sum, familiarity memory can be specifically assessed using the forced-choice recognition test, it declines later than other MTL-dependent memory functions as AD progresses, and it has distinct anatomical substrates.     

Topographical recognition memory sensitive to amnestic mild cognitive impairment but not to depression

OBJECTIVE: Amnestic mild cognitive impairment (aMCI) involves episodic memory. The person who presents aMCI has a high risk of developing Alzheimer's disease (AD). However, prediction of deterioration to dementia in cases of aMCI can be confounded with depression due to lack of specificity on selective memory tests. Finding a test sensitive to aMCI but not to depression would be potentially most useful to subsequent longitudinal studies researching the neuropsychological markers of preclinical AD. We hypothesized that the performance on a topographical memory task would be sensitive to the aMCI condition, while depression would not influence such a performance. PARTICIPANTS AND METHODS: A group of 137 community-dwelling French-speaking subjects between 55 and 70 years old was administered a topographical recognition memory task. Based on aMCI and depression criteria, 45 subjects were selected and divided into four groups: 11 patients with aMCI without depression, nine depressive patients with aMCI, ten depressive patients without cognitive impairment and 15 control subjects. The remaining non-selected participants did not belong to any of the previous interest groups. RESULTS: The 'aMCI' factor had a significant effect on the topographical recognition memory task scores, while the 'depression' factor did not. The aMCI patients performed worse than the non-aMCI. CONCLUSION: Although these results were found with relatively small groups, deficits in topographical recognition memory were observed in aMCI patients and did not seem to be sensitive to depression. Further longitudinal studies are needed to examine whether deficits in topographical recognition memory are a neuropsychological marker of preclinical AD.     

A survey of memory clinics in the british isles

This survey describes the characteristics and activities of 20 memory clinics currently operating in the United Kingdom and Eire. There was broad agreement with regard to aims, objectives and general operating characteristics, but the clinics varied considerably in the number of patients assessed over a given period and in the proportion of cases diagnosed with dementia (15–98%) and Alzheimer's disease (9–80%) in the year prior to the survey.     

Do symptoms of memory impairment correspond to cognitive impairment: a cross sectional study of a clinical cohort

BACKGROUND: Symptoms of memory loss are a common complaint within the general population and a frequent reason for seeking medical advice. However, the clinical relevance of these symptoms to future development of neurodegenerative disease is uncertain. The aim of this study is to characterise a cohort of individuals with symptoms of memory loss and varying memory impairment, who will be followed longitudinally with serial neuropsychology and neuroimaging to evaluate the clinical relevance of symptoms of memory loss. METHOD: Fifty-eight subjects with symptoms of memory loss were recruited from the National Hospital for Neurology and Neurosurgery. All subjects underwent clinical assessment, APOE4 genotyping, neuroimaging and neuropsychological tests. RESULTS: Those with mild cognitive impairment (MCI) had an increased prevalence of the APOE4 allele, impaired performance on tests of memory, measures of IQ and naming compared to controls. Baseline brain volumes were decreased and ventricular size increased. Those with symptoms of memory loss but no cognitive impairment (SNCI) performed significantly worse on tests of memory than the control group. CONCLUSIONS: The MCI represent a group with multiple risk factors for progression to AD. The SNCI group may represent a heterogeneous group with some individuals in the early stages of AD whilst others' memory complaints are more likely linked to anxiety or personality traits.     

Diagnostic differentiation of mild cognitive impairment due to Alzheimer's disease using a hippocampus‐dependent test of spatial memory

The hippocampus is one of the earliest brain regions affected in Alzheimer's disease (AD) and tests of hippocampal function have the potential to detect AD in its earliest stages. Given that the hippocampus is critically involved in allocentric spatial memory, this study applied a short test of spatial memory, the 4 Mountains Test (4MT), to determine whether test performance can differentiate mild cognitive impairment (MCI) patients with and without CSF biomarker evidence of underlying AD and whether the test can distinguish patients with MCI and mild AD dementia when applied in different cultural settings. Healthy controls (HC), patients with MCI, and mild AD dementia were recruited from study sites in UK and Italy. Study numbers were: HC (UK 20, Italy 10), MCI (UK 21, Italy 14), and AD (UK 11, Italy 9). Nineteen UK MCI patients were grouped into CSF biomarker‐positive (MCI+, n = 10) and biomarker‐negative (MCI–, n = 9) subgroups. Behavioral data were correlated with hippocampal volume and cortical thickness of the precuneus and posterior cingulate gyrus. Spatial memory was impaired in both UK and Italy MCI and AD patients. Test performance additionally differentiated between MCI+ and MCI– subgroups (P = 0.001). A 4MT score of ≤8/15 was associated with 100% sensitivity and 90% specificity for detection of early AD (MCI+ and mild AD dementia) in the UK population, and with 100% sensitivity and 50% specificity for detection of MCI and AD in the Italy sample. 4MT performance correlated with hippocampal volume in the UK population and cortical thickness of the precuneus in both study populations. In conclusion, performance on a hippocampus‐sensitive test of spatial memory differentiates MCI due to AD with high diagnostic sensitivity and specificity. The observation that similar diagnostic sensitivity was obtained in two separate study populations, allied to the scalability and usability of the test in community memory clinics, supports future application of the 4MT in the diagnosis of pre‐dementia due to AD. © 2015 Wiley Periodicals, Inc.     

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.     

Coalition Against Major Diseases/European Medicines Agency biomarker qualification of hippocampal volume for enrichment of clinical trials in predementia stages of Alzheimer's disease

BackgroundRegulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development.MethodsThe Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer's Disease Neuroimaging Initiative data.ResultsThe literature review and de novo analysis were consistent with the proposed context of use, and the Committee for Medicinal Products for Human Use released an opinion in November 2011.ConclusionsWe summarize the scientific rationale and the data that supported the first qualification of an imaging biomarker by the European Medicines Agency.     

Rey verbal learning test is a useful tool for differential diagnosis in the preclinical phase of Alzheimer's disease: comparison with mild cognitive impairment and normal aging

OBJECTIVE: To confirm that performance in verbal learning and memory test (Rey's Auditory Verbal Learning Test-RAVLT) is a helpful early neuropsychological marker of dementia of Alzheimer's type (DAT). METHODS: RAVLT was administered as part of a more extensive neuropsychological battery at baseline evaluation in 116 unselected patients referred by subjective memory complaints (SMC). Patients were followed longitudinally for 2 years (average interval of 27.7+/-4 months). Seventy patients were included in the study: 27 developed probable DAT; 17 were diagnosed as cognitively normal persons and 26 were diagnosed with Mild Cognitive Impairment (MCI). Remaining patients abandoned or they did not meet the criteria for DAT, MCI or control. Performance on RAVLT at the baseline evaluation was compared between groups. RESULTS: Patients diagnosed two years later with probable DAT showed lower results, more frequently performed a score of zero at the delayed recall test (Trial 6) and had a percentage of forgetting (difference between Trials 5 and 6) higher than 75%. Score at delayed recall test and percentage of forgetting correlated with functional scales such as MMSE, Geriatric Depression Screening, Informant Questionnaire and Blessed's Dementia Rating. CONCLUSIONS: RAVLT could help to identify those patients with SMC who would progress to DAT over a few years, and also to differentiate between the preclinical phase of Alzheimer's disease, mild cognitive impairment and normal aging. A score of zero at the delayed recall test or a percentage of forgetting > or =75% in patients with SMC is suggestive of probable DAT in the future.