Blog Archives

Cognitive reserve and Alzheimer’s disease biomarkers are independent determinants of cognition

The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer’s disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury via cerebral spinal fluid t-tau, brain amyloid-β load via cerebral spinal fluid amyloid-β1–42 and vascular disease via white matter hyperintensities on T2/proton density magnetic resonance images. We included 109 cognitively normal subjects, 192 amnestic patients with mild cognitive impairment and 98 patients with Alzheimer’s disease, from the Alzheimer’s Disease Neuroimaging Initiative study, who had undergone baseline lumbar puncture and magnetic resonance imaging. We combined patients with mild cognitive impairment and Alzheimer’s disease in a group labelled ‘cognitively impaired’ subjects. Structural Abnormality Index scores, which reflect the degree of Alzheimer’s disease-like anatomic features on magnetic resonance images, were computed for each subject. We assessed Alzheimer’s Disease Assessment Scale (cognitive behaviour section) and mini-mental state examination scores as measures of general cognition and Auditory–Verbal Learning Test delayed recall, Boston naming and Trails B scores as measures of specific domains in both groups of subjects. The number of errors on the American National Adult Reading Test was used as a measure of environmental enrichment provided by educational and occupational attainment, a component of cognitive reserve. We found that in cognitively normal subjects, none of the biomarkers correlated with the measures of cognition, whereas American National Adult Reading Test scores were significantly correlated with Boston naming and mini-mental state examination results. In cognitively impaired subjects, the American National Adult Reading Test and all biomarkers of neuronal pathology and amyloid load were independently correlated with all cognitive measures. Exceptions to this general conclusion were absence of correlation between cerebral spinal fluid amyloid-β1–42 and Boston naming and Trails B. In contrast, white matter hyperintensities were only correlated with Boston naming and Trails B results in the cognitively impaired. When all subjects were included in a flexible ordinal regression model that allowed for non-linear effects and interactions, we found that the American National Adult Reading Test had an independent additive association such that better performance was associated with better cognitive performance across the biomarker distribution. Our main conclusions included: (i) that in cognitively normal subjects, the variability in cognitive performance is explained partly by the American National Adult Reading Test and not by biomarkers of Alzheimer’s disease pathology; (ii) in cognitively impaired subjects, the American National Adult Reading Test, biomarkers of neuronal pathology (structural magnetic resonance imaging and cerebral spinal fluid t-tau) and amyloid load (cerebral spinal fluid amyloid-β1–42) all independently explain variability in general cognitive performance; and (iii) that the association between cognition and the American National Adult Reading Test was found to be additive rather than to interact with biomarkers of Alzheimer’s disease pathology.

from Brain

Performance on a measure of category fluency in cognitively impaired elderly

Measures of verbal fluency are widely used in the assessment of cognitive functioning of the elderly. However, limited research has evaluated patterns (across specific timed intervals) of performance on tasks of language fluency in different forms of dementia. The current study investigated semantic fluency in 488 elderly individuals (249 with Alzheimer’s dementia, 97 Vascular dementia, 97 Mild Cognitive Impairment and 45 cognitively intact) across 15-second intervals in an animal naming task using retrospective chart review. Normal controls produced significantly more exemplars and AD patients produced fewer animal names than the other groups. After the first 15- second time interval, the demented groups produced significantly fewer exemplars than the non-demented. At the end of 30 seconds it was possible to differentiate normal aging from MCI who no longer differed from the VaD group. Overall, it appears that the greatest and most clinically meaningful differences between the diagnostic groups were detected in the first three 15-second intervals. The present findings support the use of time intervals and total scores on tasks of verbal fluency in clinical settings and for research purposes.

from Aging, Neuropsychology, and Cognition

Morphological Cerebral Correlatesof CERAD Test Performance in Mild Cognitive Impairment and Alzheimer’s Disease

The objective of this study was to investigate the associations between structural cerebral changes and neuropsychological deficits in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Sixty patients with MCI, 34 patients with mild to moderate AD, and 32 healthy controls underwent both extensive neuropsychological assessment (CERAD test battery) and high-resolution structural magnetic resonance imaging. We used optimized voxel based morphometry to investigate (i) differences in gray matter density between the three aforementioned groups and (ii) the putative relations of CERAD test performance with atrophic brain changes. When compared to the healthy controls, the AD patients and, to a lesser extent, patients with MCI showed significant density losses predominantly in the medial temporal lobe. Deficits in verbal fluency and word finding were significantly correlated with left fronto-temporal and left temporal (including the hippocampus) changes, respectively. Decreased scores in immediate and delayed recall and in delayed recognition were associated with several cortical and subcortical sites including the parahippocampal and posterior cinguli gyri, the right thalamus, and the right hippocampus, whereas deficits in constructional praxis and constructional praxis recall referred to sites in the left thalamus and cerebellum, and the temporal cortices (bilaterally), respectively. Our findings lend further support for medial temporal lobe degeneration in MCI and AD and demonstrate that cognitive deficits as assessed on the CERAD do not simply refer to specific changes in discrete cerebral sites but rather reflect morphological alterations in widespread networks.

from the Journal of Alzheimer’s Disease

Heterogeneity of Cognitive Trajectories in Diverse Older Persons

This study examined trajectories of cognitive change in psychometrically matched measures of episodic memory, semantic memory, and executive function in an ethnically, demographically, and cognitively diverse sample of older persons. Individual rates of change showed considerable heterogeneity in each domain. Baseline clinical diagnosis predicted differential change in semantic memory and executive function, dementia > mild cognitive impairment (MCI) > normal, but average decline in verbal episodic memory was similar across all 3 diagnostic groups. There was substantial overlap of distributions of cognitive change across baseline diagnostic groups for all 3 measures. Cognitive change was strongly related to change in clinical diagnosis. Rapid and similar change was present for all 3 cognitive measures in patients with dementia and in those with normal cognition and those with MCI who progressed clinically. In cognitively normal patients, verbal episodic memory change was greater than change in the other two domains. Global status, measured by the Clinical Dementia Rating scale (Morris, 1993), predicted change in semantic memory and executive function, whereas APOE genotype predicted change in verbal episodic memory, and age had no effect on rates of change in any domain independent of global status and APOE. Results show important limitations in using cross-sectional diagnosis to predict prognosis and suggest that research to identify robust predictors of cognitive change across the full spectrum from normal to dementia is needed for better early identification of diseases that cause progressive decline.

from Psychology and Aging

Comparison of verbal memory impairment rates in mild cognitive impairment

There are no accepted guidelines establishing the most sensitive neuropsychological methods to define memory impairment in mild cognitive impairment (MCI). We investigated whether similar impairment rates were observed between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Logical Memory (LM) in 90 patients with amnestic or amnestic plus MCI. On HVLT-R delayed recall, 80% of participants performed in the MCI range compared to only 32.2% on LM II. The same pattern was seen for both amnestic and amnestic plus subtypes. Individuals impaired on HVLT-R delayed recall performed significantly worse on LM first recall and on delayed recall of LM Story A than those not impaired. MCI patients with executive dysfunction performed significantly worse than patients with no executive impairment on both LM I and HVLT-R Total Learning, but not for delayed recall of either measure. Future studies can address the longitudinal course of impairment on these measures.

from the Journal of Clinical and Experimental Neuropsychology

Cortical Activation during Clock Reading as a Quadratic Function of Dementia State

In patients with Alzheimer’s disease (AD), neuroimaging studies have demonstrated decreased brain activation, while increased activation was detected in patients with mild cognitive impairment (MCI). It can be hypothesized that increased cerebral activity seen in patients with MCI reflects neural compensation at the beginning of neurodegenerative processes. Later, as patients develop AD, neural integrity is increasingly impaired. This is accompanied by decreased neural activation. In this study we examined cognitive performance and functional magnetic resonance imaging activation on a Clock Reading task (CRT) and a Spatial Control task (SCT) in healthy controls, patients with MCI, and patients with early AD. Correlations between neural-functional activation and cognitive state, measured by the Mini Mental Status Examination, were determined using rank, linear and quadratic correlation models. It could be shown that CRT, in comparison to SCT, specifically activates brain regions in the ventral visual stream and precuneus known to be involved in conceptual processing and spatial imagery. The correlation between brain activity and cognitive state followed a quadratic rather than a linear pattern in several brain regions, including the lingual gyrus, cuneus, and precuneus. The strongest brain activity was found in patients with MCI and less severely impaired early AD subjects. These findings support the hypothesis that patients in early stages of dementia compensate for neuronal loss by the recruitment of additional neural resources reflected by increased neural activation, as measured by the blood oxygen level-dependent signal.

from the Journal of Alzheimer’s Disease

Comparison of verbal memory impairment rates in mild cognitive impairment

There are no accepted guidelines establishing the most sensitive neuropsychological methods to define memory impairment in mild cognitive impairment (MCI). We investigated whether similar impairment rates were observed between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Logical Memory (LM) in 90 patients with amnestic or amnestic plus MCI. On HVLT-R delayed recall, 80% of participants performed in the MCI range compared to only 32.2% on LM II. The same pattern was seen for both amnestic and amnestic plus subtypes. Individuals impaired on HVLT-R delayed recall performed significantly worse on LM first recall and on delayed recall of LM Story A than those not impaired. MCI patients with executive dysfunction performed significantly worse than patients with no executive impairment on both LM I and HVLT-R Total Learning, but not for delayed recall of either measure. Future studies can address the longitudinal course of impairment on these measures.

from Journal of Clinical and Experimental Neuropsychology

Verbal fluency deficits co-occur with memory deficits in geriatric patients at risk for dementia: Implications for the concept of mild cognitive impairment

We tested the notion that patients at high risk for progression to Alzheimer’s disease (AD) display relatively isolated memory deficits by assessing the relationship between memory and fluency performances in a sample of 92 geriatric subjects with cognitive complaints and normal to mild clinical presentations. Patient groups were formed on the basis of memory test scores. Patients with normal memory scores also performed normally on fluency tests, and their fluency scores were significantly higher than those of patients with low memory performances. Patients falling between these two groups in memory abilities also displayed intermediate level fluency performances. Whereas the normal memory group performed at equivalent levels on semantic and phonemic fluency tasks, both the impaired memory group and the intermediate group displayed relatively greater weaknesses in semantic fluency. This pattern is similar to that seen in AD. Since the impaired memory patients meet criteria for Amnestic Mild Cognitive Impairment, these findings suggest that memory deficits in “pre-clinical” AD are likely to be accompanied by fluency weaknesses, with semantic fluency weaknesses predominating.

from Behavioural Neurology

Diagnostic Accuracy of Percent Retention Scores on RBANS Verbal Memory Subtests for the Diagnosis of Alzheimer’s Disease and Mild Cognitive Impairment

Previous research has supported the use of percent retention scores in the neuropsychological assessment of memory, and many widely used memory measures provide for the calculation and normative comparison of these scores. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), an increasingly utilized assessment tool for cognitive impairment, provides normative data on delayed memory total raw scores only. The current study was aimed at determining the diagnostic accuracy of a novel percent retention score calculated from RBANS verbal memory subtests (delayed recall minus last learning trial) when distinguishing between normal controls, individuals diagnosed with Mild Cognitive Impairment, and individuals diagnosed with Alzheimer’s disease. Results revealed excellent diagnostic accuracy of the RBANS percent retention scores when discriminating between the three groups. Findings suggest that RBANS percent retention scores provide excellent diagnostic accuracy offering supplementary information to clinicians and researchers alike.

from Archives of Clinical Neuropsychology

Correlation of auditory event-related potentials and magnetic resonance spectroscopy measures in mild cognitive impairment

This study was aimed to examine the changes in auditory event-related potentials (AERPs) and their relationship with brain metabolic changes in mild cognitive impairment (MCI). 34 MCI patients and 34 healthy elderly controls were subjected to auditory stimulus oddball task, and then post-stimulus potentials (P50, N100, P200, N200, P300) were obtained, levels of N-acetylaspartate (NAA), creatine (Cr) and the ratio of NAA/Cr were measured by proton magnetic resonance spectroscopy (1H-MRS) in left frontal, left temporal and right parietal cortex. Compared with the control group, the MCI group had significantly increased P50 amplitudes and P300 latency, and the NAA/Cr was abnormal. Linear progression analysis revealed a strong negative correlation between P50 amplitudes and NAA/ Cr in left frontal cortex, and negative correlation between P300 latency and NAA/Cr in left frontal and left temporal, as well as correlation of AERP components and MRS metabolites with clinical scores of cognitive tests. These findings suggest that metabolic abnormalities of different brain regions may reflect the changes of underlying brain activities that are instrumental in the MCI. Therefore AERPs and MRS measurements may offer a mean to track changes of brain activities associated with functional changes, and to assess early cognitive impairment in MCI.

from Brain Research

Correlation of auditory event-related potentials and magnetic resonance spectroscopy measures in mild cognitive impairment

This study was aimed to examine the changes in auditory event-related potentials (AERPs) and their relationship with brain metabolic changes in mild cognitive impairment (MCI). 34 MCI patients and 34 healthy elderly controls were subjected to auditory stimulus oddball task, and then post-stimulus potentials (P50, N100, P200, N200, P300) were obtained, levels of N-acetylaspartate (NAA), creatine (Cr) and the ratio of NAA/Cr were measured by proton magnetic resonance spectroscopy (1H-MRS) in left frontal, left temporal and right parietal cortex. Compared with the control group, the MCI group had significantly increased P50 amplitudes and P300 latency, and the NAA/Cr was abnormal. Linear progression analysis revealed a strong negative correlation between P50 amplitudes and NAA/ Cr in left frontal cortex, and negative correlation between P300 latency and NAA/Cr in left frontal and left temporal, as well as correlation of AERP components and MRS metabolites with clinical scores of cognitive tests. These findings suggest that metabolic abnormalities of different brain regions may reflect the changes of underlying brain activities that are instrumental in the MCI. Therefore AERPs and MRS measurements may offer a mean to track changes of brain activities associated with functional changes, and to assess early cognitive impairment in MCI.

from Brain Research

Are subjective cognitive complaints a risk factor for dementia?

The objective is to evaluate the prognosis of subjective cognitive complaints (SCC) patients during 4-year follow-up. A prospective study on 92 SCC patients investigating their cognitive, affective and behavioural aspects. SCC patients were classified as having no objective cognitive impairment (NOCI), mild cognitive impairment (MCI), or subtypes of MCI. Results: 43 patients were found to have NOCI and 49 MCI. During the follow-up, 45.5% of NOCI patients remained unchanged, 13.9% were diagnosed as MCI and only one progressed to dementia. Of the MCI patients, 32.3% remained stable, 18.4% became demented and 4% reverted to NOCI. Visual attention, behavioural memory, long-term verbal memory, apathy and caregiver distress, provided independent predictors of progression to dementia.

from Neurological Sciences

The California Verbal Learning Test and other standard clinical neuropsychological tests to predict conversion from mild memory impairment to dementia

This study describes the neuropsychological assessment of 34 patients with questionable Alzheimer’s disease (QAD) followed up for 3 years. Several measures were selected from the California Verbal Learning Test (CVLT) and compared to other cognitive tasks to assess the best neuropsychological indices for (a) detecting early memory impairment in QAD and (b) predicting conversion to AD. Concerning detection, the results indicated that a recall measure depending on semantic categorization (short-delay cued recall) signaled a memory deficit in stable QAD patients, suggesting that episodic and semantic memory problems are involved in the early cognitive impairments of stable QAD patients. However, the conversion to AD was best predicted by the initial performance at the recency index (score reflecting high reliance on working memory), corroborating the idea that AD patients (even at the questionable stage) essentially rely on preserved phonological loop functioning in memory tasks. Finally, an additional impairment in visuospatial memory (Rey’s figure) provided a good discriminant value to distinguish converters from stable QAD patients, showing that various cognitive disabilities deteriorate in AD.

from the Journal of Clinical and Experimental Neurophysiology

The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer’s disease

Semantic deficits in Alzheimer’s disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer’s disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in both aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior pre-frontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.

from Neuropsychologia

Test-retest discourse performance of individuals with mild cognitive impairment

Conclusions: Extended serial reassessment is indicated in order to more fully characterise discourse production performance in MCI over time.

from Aphasiology