The apolipoprotein (APOE) ε4 allele has been proposed as an example of an antagonistic pleiotropy gene, conferring a beneficial effect on cognition in early life and a detrimental impact on cognition during later years. However, findings on the cognitive associations of the ε4 allele in younger persons are mixed. This PRISMA conforming study aimed to investigate APOE genotype (e4/non-e4) associations across seven cognitive domains (intelligence/achievement, attention/working memory, executive functioning, memory, language, processing speed and visuospatial abilities) in younger humans using a meta-analytic approach. Of 689 records reviewed, 29 studies (34 data-points) were selected for the quantitative synthesis. Participants' ages ranged from 2-40. Results showed that young ε4 carriers did not statistically differ from non-ε4 carriers across any cognitive domains. Overall, findings do not provide compelling support for an antagonistic pleiotropic effect of the ε4 allele across the lifespan.

Bilinguals' ability to control which language they speak and to switch between languages may rely on neurocognitive mechanisms shared with non-linguistic task switching. However, recent studies also reveal some limitations on the extent control mechanisms are shared across domains, introducing the possibility that some control mechanisms are unique to language. We investigated this hypothesis by directly comparing the neural correlates of task switching and language switching. Nineteen Spanish-English bilingual university students underwent a functional magnetic resonance imaging (fMRI) study employing a hybrid (event-related and blocked) design involving both color-shape switching and language switching paradigms. We compared the two switching tasks using within-subject voxel-wise t-tests for each of three trial types (single trials in single blocks, and stay and switch trials in mixed blocks). Comparing trial types to baseline in each task revealed widespread activation for single, stay, and switch trials in both color-shape and language switching. Direct comparisons of each task for each trial type revealed few differences between tasks on single and switch trials, but large task differences during stay trials, with more widespread activation for the non-linguistic than for the language task. Our results confirm previous suggestions of shared mechanisms of switching across domains, but also reveal bilinguals have greater efficiency for sustaining the inhibition of the non-target language than the non-target task when two responses are available. This efficiency of language control might arise from bilinguals' need to control interference from the non-target language specifically when not switching languages, when speaking in single- or mixed-language contexts.

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.

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer's dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer's disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers.

We examined the relationships of antemortem vascular risk factors to postmortem cerebrovascular and Alzheimer's disease (AD) pathologies. Eighty-four AD patients underwent an assessment of vascular risk (blood pressure, cholesterol, smoking, cardiovascular disease, diabetes, atrial fibrillation, transient ischemic attack [TIA], or stroke) and later underwent brain autopsy. Given our aim to examine mild cerebrovascular changes (CVCs), individuals were excluded if autopsy revealed large stroke. The most common forms of CVC were circle of Willis atherosclerosis followed by arteriosclerosis, lacunes, and microinfarcts. Excluding the history of TIA/clinical stroke, individual vascular risk factors were not associated with CVC. However, the presence of multiple vascular risk factors was associated with CVC. Furthermore, the presence of CVC was associated with lower Braak and Braak stage. These findings highlight the importance of aggregate risk in the vascular contribution to dementia. Interventions designed to maintain cerebrovascular health may represent important opportunities for preventing or delaying dementia, even when AD is the dominant pathology.

Objective

We examined BOLD (Blood-Oxygen-Level Dependent) activity reduction upon stimuli repetition of face-name pairs in older adults with amnestic (aMCI) and non-amnestic (naMCI) mild cognitive impairment diagnosed using a comprehensive actuarial method, and relationships between activity reduction and behavioral indices.

Method

Twenty-nine cognitively healthy older adults (CHs) and 20 with MCI (n = 12 aMCI; n = 8 naMCI) underwent functional MRI event-related imaging, a comprehensive neuropsychological battery, and 1-year follow-up exam. During scanning, participants were shown face-name pairs 1-3 times and administered a post-scan recognition task.

Results

The MCI group demonstrated less activity reduction upon repetition of face-name pairs within the MTL and other regions compared to CHs. Less activity reduction was associated with poorer Time 1 neuropsychological performance for the CH group and poorer post-scan recognition performance for the MCI group. Less activity reduction was related to poorer neuropsychological performance at Time 2 in the MCI group. Within MCIs, those with aMCI demonstrated less activity reduction upon repetition of face-name pairs than those with naMCI.

Conclusions

Distinct patterns of brain activity were identified in the MCI group compared to CHs, and aMCI compared to naMCI. Activated regions were not restricted to traditional memory circuitry, implicating a wider network of regions involved in the encoding of associative tasks. Findings add support to the hypothesis that lack of reduced BOLD activity reflects "faulty adaptation" to repeated stimuli and that reduction in activity represents successful encoding processes. They also provide further support for use of the face-name paradigm as a marker of prodromal Alzheimer's disease, and method to distinguish between MCI subtypes.