Neuropsychological Deficit Profiles, Vascular Risk Factors, and Neuropathological Findings in Hispanic Older Adults with Autopsy-Confirmed Alzheimer's Disease.

This study aimed to determine if patterns of neuropsychological deficits, vascular risk factors, and neuropathology differ in Hispanic and Non-Hispanic patients with autopsy-confirmed Alzheimer's disease (AD). Participants were enrolled in a longitudinal study at the Shiley-Marcos AD Research Center at the University of California, San Diego. Hispanic (n = 14) and Non-Hispanic (n = 20) patients with autopsy-confirmed AD who scored ≥95 on the Dementia Rating Scale (DRS) were included. Patient groups were matched on age, education, global mental status, and severity of functional decline; they were compared to Hispanic (n = 14) or Non-Hispanic (n = 20) cognitively-normal controls of similar age and education. Ethnicity (Hispanic, Non-Hispanic) by disease state (autopsy-confirmed AD or cognitively normal) comparisons were made for cognitive test performance and vascular risk factors. Patient groups were further compared on measures of AD (Braak stage, neuritic plaques, neurofibrillary tangles), vascular neuropathology, and performance across cognitive domains of memory, language, attention, executive functions, and visuospatial abilities after scores were z-transformed based on respective culturally-appropriate control groups. Patient groups had similar overall AD pathology burden, whereas Hispanics with AD had more small parenchymal arteriolar disease and amyloid angiopathy than Non-Hispanics with AD. Despite largely similar pathology, Hispanics with AD were less cognitively impaired (relative to respective NC groups) than Non-Hispanics with AD, and exhibited a different pattern of deficits across cognitive domains. Findings suggest that cognitive deficits that are usually prominent in AD may be less salient in Hispanic patients and this may adversely impact the ability to clinically detect the disease in mild to moderate stages.

White Matter Associations With Performance Validity Testing in Veterans With Mild Traumatic Brain Injury: The Utility of Biomarkers in Complicated Assessment.

OBJECTIVE: Failure on performance validity tests (PVTs) is common in Veterans with histories of mild traumatic brain injury (mTBI), leading to questionable validity of clinical presentations. PARTICIPANTS: Using diffusion tensor imaging, we investigated white matter (WM) integrity and cognition in 79 Veterans with history of mTBI who passed PVTs (n = 43; traumatic brain injury [TBI]-passed), history of mTBI who failed at least 1 PVT (n = 13; TBI-failed), and military controls (n = 23; MCs) with no history of TBI. RESULTS: The TBI-failed group demonstrated significantly lower cognitive scores relative to MCs and the TBI-passed group; however, no such differences were observed between MCs and the TBI-passed group. On a global measure of WM integrity (ie, WM burden), the TBI-failed group showed more overall WM abnormalities than the other groups. However, no differences were observed between the MCs and TBI-passed group on WM burden. Interestingly, regional WM analyses revealed abnormalities in the anterior internal capsule and cingulum of both TBI subgroups relative to MCs. Moreover, compared with the TBI-passed group, the TBI-failed group demonstrated significantly decreased WM integrity in the corpus callosum. CONCLUSIONS: Findings revealed that, within our sample, WM abnormalities are evident in those who fail PVTs. This study adds to the burgeoning PVT literature by suggesting that poor PVT performance does not negate the possibility of underlying WM abnormalities in military personnel with history of mTBI.

Assessment of Alzheimer's disease risk with functional magnetic resonance imaging: an arterial spin labeling study.

Functional magnetic resonance imaging (fMRI) of older adults at risk for Alzheimer's disease (AD) by virtue of their cognitive (i.e., mild cognitive impairment [MCI]) and/or genetic (i.e., apolipoprotein E [APOE] ε4 allele) status demonstrate divergent brain response patterns during memory encoding across studies. Using arterial spin labeling MRI, we examined the influence of AD risk on resting cerebral blood flow (CBF) as well as the CBF and blood oxygenation level dependent (BOLD) signal response to memory encoding in the medial temporal lobes (MTL) in 45 older adults (29 cognitively normal [14 APOE ε4 carriers and 15 noncarriers]; 16 MCI [8 APOE ε4 carriers, 8 noncarriers]). Risk groups were comparable in terms of mean age, years of education, gender distribution, and vascular risk burden. Individuals at genetic risk for AD by virtue of the APOE ε4 allele demonstrated increased MTL resting state CBF relative to ε4 noncarriers, whereas individuals characterized as MCI showed decreased MTL resting state CBF relative to their cognitively normal peers. For percent change CBF, there was a trend toward a cognitive status by genotype interaction. In the cognitively normal group, there was no difference in percent change CBF based on APOE genotype. In contrast, in the MCI group, APOE ε4 carriers demonstrated significantly greater percent change in CBF relative to ε4 noncarriers. No group differences were found for BOLD response. Findings suggest that abnormal resting state CBF and CBF response to memory encoding may be early indicators of brain dysfunction in individuals at risk for developing AD.

Neuropsychological assessment of dementia.

Neuropsychological studies show that cognitive deficits associated with Alzheimer's disease (AD) are distinct from age-associated cognitive decline. Quantitative and qualitative differences are apparent across many cognitive domains, but are especially obvious in episodic memory (particularly delayed recall), semantic knowledge, and some aspects of executive functions. The qualitatively distinct pattern of deficits is less salient in very old AD patients than in younger AD patients. Although decline in episodic memory is usually the earliest cognitive change that occurs prior to the development of the AD dementia syndrome, asymmetry in cognitive abilities may also occur in this "preclinical" phase of the disease and predict imminent dementia. Discrete patterns of cognitive deficits occur in AD and several neuropathologically distinct age-associated neurodegenerative disorders. Knowledge of these differences helps to clinically distinguish among various causes of dementia and provides useful models for understanding brain-behavior relationships that mediate cognitive abilities affected in various neurodegenerative diseases.

The myth of testing construct validity using factor analysis or correlations with normal or mixed clinical populations: lessons from memory assessment.

For nearly a century, the primary method employed by psychologists to define and test the validity of constructs evaluated by assessment instruments has been shared-variance techniques such as intervariable correlations or factor analysis with large normative or mixed clinical samples. To illustrate the shortcomings of this approach, we conducted (1) correlational analyses of immediate- and delayed-memory measures separately in normal participants and in homogeneous samples of patients with either Alzheimer's disease or Huntington's disease; and (2) factor analysis of immediate and delayed-recall and recognition measures in a large, homogeneous sample of patients with Alzheimer's disease. The findings revealed that cognitive measures that share variance in the intact brain-thereby giving the facade of assessing a unitary construct-can dissociate and contribute to unique variance in the damaged brain, but only if the pathology occurs in brain regions known to disrupt vital cognitive processes tapped by those measures. The results illustrate that shared-variance procedures applied to normal or mixed clinical populations can mask some of the most vital cognitive constructs, such as the classic distinction between short- and long-term memory. Implications of these findings for research and clinical practice are discussed.