Nadia Pare

Verbal fluency performance in amnestic MCI and older adults with cognitive complaints

Verbal fluency tests are employed regularly during neuropsychological assessments of older adults, and deficits are a common finding in patients with Alzheimers disease (AD). Little extant research, however, has investigated verbal fluency ability and subtypes in preclinical stages of neurodegenerative disease. We examined verbal fluency performance in 107 older adults with amnestic mild cognitive impairment (MCI, n=37), cognitive complaints (CC, n=37) despite intact neuropsychological functioning, and demographically matched healthy controls (HC, n=33). Participants completed fluency tasks with letter, semantic category, and semantic switching constraints. Both phonemic and semantic fluency were statistically (but not clinically) reduced in amnestic MCI relative to cognitively intact older adults, indicating subtle changes in the quality of the semantic store and retrieval slowing. Investigation of the underlying constructs of verbal fluency yielded two factors: Switching (including switching and shifting tasks) and Production (including letter, category, and action naming tasks), and both factors discriminated MCI from HC albeit to different degrees. Correlational findings further suggested that all fluency tasks involved executive control to some degree, while those with an added executive component (i.e., switching and shifting) were less dependent on semantic knowledge. Overall, our findings highlight the importance of including multiple verbal fluency tests in assessment batteries targeting preclinical dementia populations and suggest that individual fluency tasks may tap specific cognitive processes.

Differential Memory Test Sensitivity for Diagnosing Amnestic Mild Cognitive Impairment and Predicting Conversion to Alzheimer's Disease

ABSTRACT Episodic memory is the first and most severely affected cognitive domain in Alzheimers disease (AD), and it is also the key early marker in prodromal stages including amnestic mild cognitive impairment (MCI). The relative ability of memory tests to discriminate between MCI and normal aging has not been well characterized. We compared the classification value of widely used verbal memory tests in distinguishing healthy older adults (n = 51) from those with MCI (n = 38). Univariate logistic regression indicated that the total learning score from the California Verbal Learning Test-II (CVLT-II) ranked highest in terms of distinguishing MCI from normal aging (sensitivity = 90.2; specificity = 84.2). Inclusion of the delayed recall condition of a story memory task (i.e., WMS-III Logical Memory, Story A) enhanced the overall accuracy of classification (sensitivity = 92.2; specificity = 94.7). Combining Logical Memory recognition and CVLT-II long delay best predicted progression from MCI to AD over a 4-year period (accurate classification = 87.5%). Learning across multiple trials may provide the most sensitive index for initial diagnosis of MCI, but inclusion of additional variables may enhance overall accuracy and may represent the optimal strategy for identifying individuals most likely to progress to dementia.

Selective Changes in White Matter Integrity in MCI and Older Adults with Cognitive Complaints

BACKGROUND White matter changes measured using diffusion tensor imaging have been reported in Alzheimers disease and amnestic mild cognitive impairment, but changes in earlier pre-mild cognitive impairment stages have not been fully investigated. METHODS In a cross-sectional analysis, older adults with mild cognitive impairment (n=28), older adults with cognitive complaints but without psychometric impairment (n=29) and healthy controls (n=35) were compared. Measures included whole-brain diffusion tensor imaging, T1-weighted structural magnetic resonance imaging, and neuropsychological assessment. Diffusion images were analyzed using Tract-Based Spatial Statistics. Voxel-wise fractional anisotropy and mean, axial, and radial diffusivities were assessed and compared between groups. Significant tract clusters were extracted in order to perform further region of interest comparisons. Brain volume was estimated using FreeSurfer based on T1 structural images. RESULTS The mild cognitive impairment group showed lower fractional anisotropy and higher radial diffusivity than controls in bilateral parahippocampal white matter. When comparing extracted diffusivity measurements from bilateral parahippocampal white matter clusters, the cognitive complaint group had values that were intermediate to the mild cognitive impairment and healthy control groups. Group difference in diffusion tensor imaging measures remained significant after controlling for hippocampal atrophy. Across the entire sample, diffusion tensor imaging indices in parahippocampal white matter were correlated with memory function. CONCLUSIONS These findings are consistent with previous results showing changes in parahippocampal white matter in Alzheimers disease and mild cognitive impairment compared to controls. The intermediate pattern found in the cognitive complaint group suggests the potential of diffusion tensor imaging to contribute to earlier detection of neurodegenerative changes during prodromal stages. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Visual contrast sensitivity in Alzheimer’s disease, mild cognitive impairment, and older adults with cognitive complaints

Deficits in contrast sensitivity (CS) have been reported in Alzheimers disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.

The Memory and Aging Telephone Screen: Development and preliminary validation

Telephone interviews are widely used in geriatric settings to identify eligible research participants and to perform brief follow‐up assessments of cognition. This article reports on the development and validation of the Memory and Aging Telephone Screen (MATS), a structured interview for older adults with mild cognitive impairment and/or significant memory complaints. We also developed three alternate forms of the MATS objective memory test to reduce practice effects engendered by multiple administrations.

Neural correlates of semantic processing in older adults with cognitive complaints and amnestic MCI

Background: The technique of Near-Infrared Spectroscopy (NIRS) is a noninvasive optical method allowing the in vivo measurement of brain oxygenation by assessing changes in the concentration of oxy[O2Hb] and deoxygenated [HHb] haemoglobin in the cerebral cortex. Recent studies show that controls display a typical activation pattern during a verbal fluency task (mainly involving prefrontal areas). We expected that patients suffering from Alzheimer’s disease display altered activation patterns that progress over time. Methods: 66 AD-patients and 68 age and gender matched healthy controls were measured during two versions of a verbal fluency task (VFT; letter and category using weekdays as a control task) using 44-channel NIRS. 8 patients and 16 controls completed a follow-up measurement after one year. Results: During both versions of the VFT AD-patients showed deficient activation over frontal areas as compared to healthy controls with more distinct differences in the letter version. The activation in frontal areas correlated positively with the behavioural performance during the VFT and also with the severity of AD as assessed with neuropsychological tests. After one year AD-patients showed decreased activation in five NIRS-channels covering the left dorsolateral prefrontal cortex, whereas controls showed no significant changes over the one-year interval. The activation changes in the deficient ‘‘frontal cluster’’ were correlated with the decrease of the MMSE score, with greater decrease indicating lower MMSE score at the follow-up. Conclusions: NIRS seems to be a well suited instrument to measure disease related changes in the cortex of AD patients and their progression over time. As alternations in oxygenation probably occur before atrophy in affected brain regions, NIRS could perhaps be used to develop methods for the early detection of AD.

P2-095: Working memory activation in mild cognitive impairment and older adults with cognitive complaints

non-verbal fluid type intelligence (Raven’s Standard Progressive Matrices test [RPM]). From this sample, 52 individuals (aged 69/70) with an age 11 IQ between 85 and 115 and who had a RPM of 34 (group mean 0.5 SD), representing those who had cognitive decline (decliners, n 27) or a score of 41 (group mean 0.5 SD) representing successful ageing (sustainers, n 25) were recruited into this functional MRI study. Working memory was assessed with a two-condition N-Back task. Fifteen participants failed to complete the task because of an inability to correct vision, feeling unwell or scoring below 50% correct for the 2-Back task. Results: In a comparison of the high load working memory task (2-Back) with rest, extensive differences in activation were found in the cognitive decliners compared with the sustainers in the frontal, parietal and cerebellar regions. Conclusions: These data add to the evidence that prefrontal cortical regions are important in maintaining working memory as people age. Parietal and cerebellar regions are also involved in working memory; however their importance in successful cognitive ageing is unclear.