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 Alzheimer's 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 Alzheimer's 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.

Development and psychometric evaluation of the Test of Practical Judgment alternate form (Form B).

The Test of Practical Judgment (TOP-J) is increasingly used by neuropsychologists to measure everyday judgment ability in older adulthood. In the present study, we developed an alternate TOP-J Form B, which may be used to reduce practice effects for repeat assessment situations or in place of the original Form A. In developing the measure, special attention was given to limiting cultural bias and making items similar in content and difficulty to Form A. The TOP-J Form B was piloted in a clinical geriatric sample (N = 77) in the Midwestern U.S. Subsequently, older adults (N = 130) were recruited from several boroughs of New York City and surrounding areas (mean age = 77; mean years of education = 16; 69% female; 28% Black/African-American, 11% Hispanic). In this validation sample, both the 9-item and 15-item versions of the TOP-J Form B showed strong psychometric properties, including good unidimensional model fit in confirmatory factor analysis, preliminary convergent/divergent and criterion validity evidence, and strong inter-rater reliability, ICC (2, 1) = .93. The means and standard deviations for the TOP-J Form A and Form B were highly similar, particularly for the 9-item forms in which there was less than a one-point mean difference. Preliminary normative data for cognitively intact participants (n = 73) were established. We present means and standard deviations that will allow for the calculation of z scores as Form B scores were normally distributed. The newly developed TOP-J Form B should be useful in diverse clinical and research settings.

Informant report of practical judgment ability in a clinical sample of older adults with subjective cognitive decline, mild cognitive impairment, and dementia.

Despite the importance of capturing problems with judgment and decision-making during neuropsychological evaluations of older adults, there are a limited number of validated measures and no informant rating scales. We developed an informant measure that captures compromised judgment related to safety, medical, financial, and social-ethical issues After item refinement and piloting in a memory disorders clinic, we utilized the Test of Practical Judgment-Informant (TOP-J-Informant) at two clinics in the Midwestern U.S., including 189 patient/informant dyads (mean age = 79.0, median years of education = 13, % female = 67.7) with various preclinical and clinical dementia conditions. We found psychometric support, including evidence for convergent, divergent, and criterion-related validity, and internal consistency. Importantly, we were able to discriminate between diagnostic groups in the expected direction. The TOP-J-Informant is brief (<5 minutes), easy to administer, and can reveal areas of concern related to poor judgment when administered in the context of a neuropsychological evaluation or clinic visit.

The Memory and Aging Telephone Screen: development and preliminary validation.

BACKGROUND: 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. METHODS: Participants were enrolled in a longitudinal study that included 120 older adults with amnestic mild cognitive impairment, subjective cognitive complaints but without deficit on neuropsychological tests, and demographically matched healthy controls. An additional 15 patients with mild probable Alzheimer's disease completed the alternative forms study. All participants received the original MATS version, and a subset (n = 90) later received two of three alternate forms. RESULTS: The MATS was sensitive to group differences, and the alternate forms were equivalent. MATS objective memory test scores showed adequate stability during a period of 1 year and were moderately correlated with scores on a widely used list-learning test (California Verbal Learning Test, Second Edition). CONCLUSIONS: The MATS, a repeatable telephone screen that includes objective and subjective memory assessments, is useful for detecting individuals in the preclinical and early stages of dementia. Results encourage use of the MATS as a reliable and valid cognitive screening tool in research and clinical settings. Longitudinal assessments are being performed to investigate the predictive validity of the MATS for cognitive progression in mild cognitive impairment.

Self- and informant reports of executive function on the BRIEF-A in MCI and older adults with cognitive complaints.

Amnestic mild cognitive impairment (MCI) is characterized by impaired episodic memory, although subtle executive problems have been noted on neuropsychological tests. Recent research also has described a group of healthy, non-depressed older adults with significant cognitive complaints (CC) but normal performance on neuropsychological testing. These individuals show structural and functional brain changes intermediate between those seen in MCI and healthy older adults without such complaints (HC). We evaluated executive functions in MCI and CC using the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), a newly developed self- and informant report questionnaire in 29 patients with amnestic MCI, 28 CCs, and 30 demographically matched HCs. MCI and CC participants reported significant difficulties with selective aspects of executive functioning relative to HCs despite clinically normal performance on neuropsychological tests of this cognitive domain. Scores were generally in the pattern of MCI>CC>HC, and findings were most pronounced for working memory. Additionally, MCI and CC participants were more likely than their informants to report clinically meaningful executive problems, though informants identified a similar pattern of difficulty overall. Results failed to reveal strong relations between the BRIEF-A and standardized neuropsychological tests of executive function. Overall findings indicate that the BRIEF-A is sensitive to subtle executive changes in MCI and CC and suggest the need for research to determine if executive complaints are predictive of clinical course.

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 Alzheimer's 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.

Mild traumatic brain injury and its sequelae: characterisation of divided attention deficits.

Deficits in divided attention occur after a mild traumatic brain injury (MTBI) but many extant tasks lack sensitivity for detecting subtle cognitive difficulties. We use the Test d'Attention Partagee Informatise (TAPI), a novel dual-task paradigm, to investigate the impact of MTBI on the ability to divide attention between two stimuli sources. Individuals with MTBI (n=37) were evaluated within the first week following head trauma and at three months post-injury. A healthy control (HC) group (n=79) was also assessed. The primary outcome was reaction time and there were three different conditions that included visual target detection and auditory digit span tasks. Analyses utilised repeated measures ANOVA and ANCOVA models that adjusted for relevant variables including post-concussive and affective symptoms. Results indicated that at both baseline and follow-up, the MTBI group had significantly slower reaction time than the HC group. Also, both the MTBI and HC groups had slower reaction times as participants progressed through each of the more challenging TAPI conditions. This study supports the usefulness of this novel instrument and allows clinicians and researchers to assess for subtle divided attention deficits that may persist in those with MTBI even three months post-injury.

Differential memory test sensitivity for diagnosing amnestic mild cognitive impairment and predicting conversion to Alzheimer's disease.

Episodic memory is the first and most severely affected cognitive domain in Alzheimer's 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.

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 Alzheimer's 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.