Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment(a MCI) to Alzheimer’s disease(AD). As a part of the medial temporal lobe memory system,the hippocampus is one of the brain regions affected earliest by AD neuropathology,and shows progressive degeneration as a MCI progresses to AD. Currently,no validated biomarkers can precisely predict the conversion from a MCI to AD. Therefore,there is a great need of sensitive tools for the early detection of AD progression. In this review,we summarize the specifi c structural and functional changes in the hippocampus from recent a MCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile,this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of a MCI to AD.     

Can clinical data predict progression to dementia in amnestic mild cognitive impairment?

BACKGROUND: To determine whether clinical data obtained by history and physical examination can predict eventual progression to dementia in a cohort of elderly people with mild cognitive impairment. METHODS: A prospective, longitudinal study of a cohort of elderly subjects with amnestic Mild Cognitive Impairment (MCI). Ninety subjects meeting the criteria for amnestic MCI were recruited and followed annually for an average of 3.3 years. Main outcome measure was the development of dementia determined by clinical assessment with confirmatory neuropsychological evaluation. RESULTS: Fifty patients (56%) developed dementia on follow-up. They were older, had lower Mini-mental status exam (MMSE) scores and a shorter duration of symptoms at the time of first assessment. Multivariate logistic regression analysis identified age at symptom onset as the only clinical parameter which distinguished the group that deteriorated to dementia from the group that did not. The odds ratio for age was 1.1 (confidence interval 1.04 - 1.18). CONCLUSIONS: Patients presenting with amnestic MCI insufficient for the diagnosis of dementia are at high risk of developing dementia on follow-up. In our cohort, 56% were diagnosed with dementia over an average period of 5.9 years from symptom onset. The only clinical predictor for the eventual development of dementia was older age at symptom onset. Clinical features alone were insufficient to predict development of dementia.     

Episodic autobiographical memory in amnestic mild cognitive impairment: What are the neural correlates?

Autobiographical memory in amnestic Mild Cognitive Impairment (aMCI) is characterized by impaired retrieval of episodic memories, but relatively preserved personal semantic knowledge. This study aimed to identify (via FDG‐PET) the neural substrates of impaired episodic specificity of autobiographical memories in 35 aMCI patients compared with 24 healthy elderly controls. Significant correlations between regional cerebral activity and the proportion of episodic details in autobiographical memories from two life periods were found in specific regions of an autobiographical brain network. In aMCI patients, more than in controls, specifically episodic memories from early adulthood were associated with metabolic activity in the cuneus and in parietal regions. We hypothesized that variable retrieval of episodic autobiographical memories in our aMCI patients would be related to their variable capacity to reactivate specific sensory‐perceptual and contextual details of early adulthood events linked to reduced (occipito‐parietal) visual imagery and less efficient (parietal) attentional processes. For recent memories (last year), a correlation emerged between the proportion of episodic details and activity in lateral temporal regions and the temporo‐parietal junction. Accordingly, variable episodic memory for recent events may be related to the efficiency of controlled search through general events likely to provide cues for the retrieval of episodic details and to the ability to establish a self perspective favouring recollection. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

False memories in patients with mild cognitive impairment and mild Alzheimer’s disease dementia: Can cognitive strategies help?

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that presents predominantly with impairments in learning and memory. Patients with AD are also susceptible to false memories, a clinically relevant memory distortion where a patient remembers an incorrect memory that they believe to be true. The use of cognitive strategies to improve memory performance among patients with AD by reducing false memories has taken on added importance given the lack of disease-modifying agents for AD. However, existing evidence suggests that cognitive strategies to reduce false memories in patients with AD are of limited effectiveness, although these strategies may be useful at earlier stages of the disease. The purpose of this review is to examine experimental findings of false memories and associated memory processes in patients with mild cognitive impairment due to AD and mild AD dementia. Cognitive strategies to reduce false memories in these patient populations are also reviewed. Approaches to clinically relevant future research are suggested and discussed.     

Can an 18-point clock-drawing scoring system predict dementia in elderly individuals with mild cognitive impairment?

The purpose of this study was to develop a clock-drawing scoring system better suited to detecting possible early markers of dementia in individuals with mild cognitive impairment (MCI). We modified the scoring system of Freedman et al. (1994), in which the major components are integrity of the circle, placement and size of the hands, and placement and sequence of the numbers. We rescored the clock-drawing test using a novel 18-point scoring system, which emphasizes hand elements-number of hands, direction indicated, and size differences. We retrospectively assessed 123 individuals (ages 58-88 years) selected from the Memory Clinic at the Jewish General Hospital in Montreal. These consisted of 21 normal elderly individuals (NORM group), 41 participants with mild cognitive impairment who did not develop dementia on follow-up visits (MCI-NP), 41 participants with mild cognitive impairment who became demented after a 48-month follow-up (MCI-D), and 20 participants diagnosed with Alzheimer's disease (AD). On the 18-point system, the MCI-NP and the MCI-D did not show any difference on overall total score (p = .166), However, using Pearson chi-squares to examine the within-categories effects comparing the mildly cognitively impaired groups (MCI-NP and MCI-D), there were three significant hand items that appear to be possible early markers of progression to dementia. The clock has two hands (p = .043), hour hand is towards correct number (p = .023), and size difference of the hands is respected (p = .004), all showed significant differences between progressors and nonprogressors. The 18-point clock-drawing scoring system may have advantages in better indicating MCI individuals more likely to progress to dementia.     

Awareness of deficits in mild cognitive impairment and Alzheimer's disease: do MCI patients have impaired insight?

In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective research program 36 consecutive patients with mild AD (MMSE above 19), 30 with amnesic MCI and 33 matched controls were examined. Using three methods for awareness assessment we found no significant differences in the level of awareness between MCI and AD. Both groups had impaired awareness and significant heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected dementia disorders.     

A parsimonious scoring and normative calculator for the Parkinson’s disease mild cognitive impairment battery

Abstract

Objective: The aim of the present study was to provide a regression-based calculator that takes premorbid functioning into account to detect subtle cognitive decline, as is often present in pre-dementia states, especially mild cognitive impairment in Parkinson’s disease (PD-MCI).

Method: We used demographic adjustments based on sex, age, and education of 699 normative participants that fulfilled exclusion criteria for ascertaining the diagnostic accuracy of the Movement Disorders Society PD-MCI battery at Level II. We examined the clinical validity of the battery on 36 PD patients.

Results: An estimated z-score was calculated for any raw score based on different models that adjust for the demographic predictors of gender, age, and education, either concurrently, individually or without covariates. We provide a useful online z-score, SD, and percentile calculator that yields estimates of cognitive impairment based on normative sample for each of the ten neuropsychological tests and enables actuarial decision-making regarding its level and profile (number of domains impaired). We document the clinical utility and applicability of the calculator on a patient with PD-MCI and show the discriminative validity of all measures in the battery by comparing PD-MCI and PD without cognitive impairment with the highest area under the curve (.94) for Tower of London at ?2 SD threshold.

Conclusions: Our normative calculator introduces a practical web-based psychometric tool for the evaluation of PD-MCI status in clinical settings. We show the detection potential of each of ten measures included in the battery and delineate the diagnostic precision of the PD-MCI battery.     

Rule induction performance in amnestic mild cognitive impairment and Alzheimer’s dementia: examining the role of simple and biconditional rule learning processes

Introduction: Rule induction tests such as the Wisconsin Card Sorting Test require executive control processes, but also the learning and memorization of simple stimulus–response rules. In this study, we examined the contribution of diminished learning and memorization of simple rules to complex rule induction test performance in patients with amnestic mild cognitive impairment (aMCI) or Alzheimer’s dementia (AD). Method: Twenty-six aMCI patients, 39 AD patients, and 32 control participants were included. A task was used in which the memory load and the complexity of the rules were independently manipulated. This task consisted of three conditions: a simple two-rule learning condition (Condition 1), a simple four-rule learning condition (inducing an increase in memory load, Condition 2), and a complex biconditional four-rule learning condition—inducing an increase in complexity and, hence, executive control load (Condition 3). Results: Performance of AD patients declined disproportionately when the number of simple rules that had to be memorized increased (from Condition 1 to 2). An additional increment in complexity (from Condition 2 to 3) did not, however, disproportionately affect performance of the patients. Performance of the aMCI patients did not differ from that of the control participants. In the patient group, correlation analysis showed that memory performance correlated with Condition 1 performance, whereas executive task performance correlated with Condition 2 performance. Conclusions: These results indicate that the reduced learning and memorization of underlying task rules explains a significant part of the diminished complex rule induction performance commonly reported in AD, although results from the correlation analysis suggest involvement of executive control functions as well. Taken together, these findings suggest that care is needed when interpreting rule induction task performance in terms of executive function deficits in these patients.     

Are people with mild cognitive impairment aware of the benefits of errorless learning?

Mild cognitive impairment (MCI) has been described as a memory deficit in the absence of other cognitive dysfunction. It can be thought of as a pre-clinical dementia. Memory impairment in this group is not as severe as in early dementia and thus learning is still possible. We were interested to see if errorless learning, a widely used rehabilitation technique, was of benefit to people with MCI. Since it has been shown that successful rehabilitation is somewhat contingent on awareness of function, we were also interested to see if people with MCI were aware of the benefits of errorless learning. The present study employed an errorless learning procedure on 16 people with MCI and 16 older adult controls to learn two lists of 10 words in errorless and errorful learning conditions. We adopted a metacognitive approach measuring people's memory monitoring through judgements of learning (JOLs) a prediction of future memory performance. The results revealed errorless learning is an effective memory rehabilitation tool for people with MCI, with significant increases in recall performance for both groups relative to errorful learning. Most interestingly participants were aware of the benefits of errorless learning in their JOLs. MCI participants and controls both had significantly higher JOLs for words studied under errorless learning conditions. The learning performance in MCI and theories of metacognitive awareness are discussed.     

Advances in longitudinal studies of amnestic mild cognitive impairment and Alzheimer’s disease based on multi-modal MRI techniques

Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease (AD), and 75%–80% of aMCI patients finally develop AD. So, early identification of patients with aMCI or AD is of great significance for prevention and intervention. According to cross-sectional studies, it is known that the hippocampus, posterior cingulate cortex, and corpus callosum are key areas in studies based on structural MRI (sMRI), functional MRI (fMRI), and diffusion tensor imaging (DTI) respectively. Recently, longitudinal studies using each MRI modality have demonstrated that the neuroimaging abnormalities generally involve the posterior brain regions at the very beginning and then gradually affect the anterior areas during the progression of aMCI to AD. However, it is not known whether follow-up studies based on multi-modal neuroimaging techniques (e.g., sMRI, fMRI, and DTI) can help build effective MRI models that can be directly applied to the screening and diagnosis of aMCI and AD. Thus, in the future, large-scale multi-center follow-up studies are urgently needed, not only to build an MRI diagnostic model that can be used on a single person, but also to evaluate the variability and stability of the model in the general population. In this review, we present longitudinal studies using each MRI modality separately, and then discuss the future directions in this field.     

Alcohol consumption in mild cognitive impairment and dementia: harmful or neuroprotective?

Objective: In several longitudinal studies, light‐to‐moderate drinking of alcoholic beverages has been proposed as being protective against the development of age‐related changes in cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia). However, contrasting findings also exist. Method: The English literature published in this area before September 2011 was evaluated, and information relating to the various factors that may impact upon the relationship between alcohol consumption and dementia or predementia syndromes is presented in the succeeding texts. Results: Light‐to‐moderate alcohol consumption may be associated with a reduced risk of incident overall dementia and AD; however, protective benefits afforded to vascular dementia, cognitive decline, and predementia syndromes are less clear. The equivocal findings may relate to many of the studies being limited to cross‐sectional designs, restrictions by age or gender, or incomplete ascertainment. Different outcomes, beverages, drinking patterns, and study follow‐up periods or possible interactions with other lifestyle‐related (e.g., smoking) or genetic factors (e.g., apolipoprotein E gene variation) may all contribute to the variability of findings. Conclusion: Protective effects of moderate alcohol consumption against cognitive decline are suggested to be more likely in the absence of the AD‐associated apolipoprotein E ε4 allele and where wine is the beverage. At present, there is no indication that light‐to‐moderate alcohol drinking would be harmful to cognition and dementia, and attempts to define what might be deemed beneficial levels of alcohol intake in terms of cognitive performance would be highly problematic and contentious. Copyright © 2012 John Wiley & Sons, Ltd.     

Advances in longitudinal studies of amnestic mild cognitive impairment and Alzheimer＇s disease based on multi-modal MRI techniques

Amnestic mild cognitive impairment （aMCI） is a prodromal stage of Alzheimer＇s disease （AD）, and 75%-80% of aMCI patients finally develop AD. So, early identification of patients with aMCI or AD is of great significance for prevention and intervention. According to cross-sectional studies, it is known that the hippocampus, posterior cingulate cortex, and corpus callosum are key areas in studies based on structural MRI （sMRI）, functional MRI （fMRI）, and diffusion tensor imaging （DTI） respectively. Recently, longitudinal studies using each MRI modality have demonstrated that the neuroimaging abnormalities generally involve the posterior brain regions at the very beginning and then gradually affect the anterior areas during the progression of aMCI to AD. However, it is not known whether follow-up studies based on multi-modal neuroimaging techniques （e.g., sMRI, fMRI, and DTI） can help build effective MRI models that can be directly applied to the screening and diagnosis of aMCI and AD. Thus, in the future, large-scale multi-center follow-up studies are urgently needed, not only to build an MRI diagnostic model that can be used on a single person, but also to evaluate the variability and stability of the model in the general population. In this review, we present longitudinal studies using each MRI modality separately, and then discuss the future directions in this field.