Disintegration at the Syntax-Semantics Interface in Prodromal Alzheimer's Disease: New Evidence from Complex Sentence Anaphora in Amnestic Mild Cognitive Impairment (aMCI).

Although diverse language deficits have been widely observed in prodromal Alzheimer's disease (AD), the underlying nature of such deficits and their explanation remains opaque. Consequently, both clinical applications and brain-language models are not well-defined. In this paper we report results from two experiments which test language production in a group of individuals with amnestic Mild Cognitive Impairment (aMCI) in contrast to healthy aging and healthy young. The experiments apply factorial designs informed by linguistic analysis to test two forms of complex sentences involving anaphora (relations between pronouns and their antecedents). Results show that aMCI individuals differentiate forms of anaphora depending on sentence structure, with selective impairment of sentences which involve construal with reference to context (anaphoric coreference). We argue that aMCI individuals maintain core structural knowledge while evidencing deficiency in syntax-semantics integration, thus locating the source of the deficit in the language-thought interface of the Language Faculty.

Neurocognitive effects of proton radiation therapy in adults with low-grade glioma.

To understand neurocognitive effects of proton radiation therapy (PRT) in patients with low-grade glioma, we evaluated 20 patients who received this therapy prospectively and over 5 years with a comprehensive neuropsychological battery. 20 patients were evaluated at baseline and at yearly intervals for up to 5 years with a battery of neuropsychological measures that assessed intellectual, attention, executive, visuospatial and memory functions as well as mood and functional status. We evaluated change in cognitive functioning over time. We analyzed the relationship between cognitive performance and tumor location and also examined whether patients' performance differed from that reported in a study of normative practice effects. Overall, patients exhibited stability in cognitive functioning. Tumor location played a role in performance; those with tumors in the left hemisphere versus in the right hemisphere were more impaired at baseline on verbal measures (p < .05). However, we found greater improvement in verbal memory over time in patients with left than with right hemisphere tumors (p < .05). Results of our study, the first to investigate, in depth, neurocognitive effects of PRT in adults with low-grade gliomas, are promising. We hypothesize that the conformal advantage of PRT may contribute to preservation of cognitive functioning, although larger sample sizes and a longer period of study are required. Our study also highlights the need to consider normative practice effects when studying neurocognitive functioning in response to treatment over time, and the need to utilize comprehensive neuropsychological batteries given our findings that differentiate patients with left and right hemisphere tumors.

Language Decline Characterizes Amnestic Mild Cognitive Impairment Independent of Cognitive Decline.

Purpose This research investigated the nature of cognitive decline in prodromal Alzheimer's disease (AD), particularly in mild cognitive impairment, amnestic type (aMCI). We assessed language in aMCI as compared with healthy aging (HA) and healthy young (HY) with new psycholinguistic assessment of complex sentences, and we tested the degree to which deficits on this language measure relate to performance in other general cognitive domains such as memory. Method Sixty-one individuals with aMCI were compared with 24 HA and 10 HY adults on a psycholinguistic measure of complex sentence production (relative clauses). In addition, HA, HY, and a subset of the aMCI participants (n = 22) were also tested on a multidomain cognitive screen, the Addenbrooke's Cognitive Examination-Revised (ACE-R), and on a verbal working memory Brown-Peterson (BP) test. General and generalized linear mixed models were used to test psycholinguistic results and to test whether ACE-R and BP performance predicted performance on the psycholinguistic test similarly in the aMCI and HA groups. Results On the psycholinguistic measure, sentence imitation was significantly deficited in aMCI in comparison with that in HA and HY. Experimental factorial designs revealed that individuals with aMCI had particular difficulty repeating sentences that especially challenged syntax-semantics integration. As expected, the aMCI group also performed significantly below the HY and HA groups on the ACE-R. Neither the ACE-R Memory subtest nor the BP total scores predicted performance on the psycholinguistic task for either the aMCI or the HA group. However, the ACE-R total score significantly predicted psycholinguistic task performance, with increased ACE-R performance predicting increased psycholinguistic task performance only for the HA group, not for the aMCI group. Conclusions Results suggest a selective deterioration in language in aMCI, specifically a weakening of syntax-semantics integration in complex sentence processing, and a general independence of this language deficit and memory decline. Results cohere with previous assessments of the nature of difficulty in complex sentence formation in aMCI. We argue that clinical screening for prodromal AD can be strengthened by supplementary testing of language, as well as memory, and extended evaluation of strength of their relation.

Representing orientation: A coordinate-system hypothesis and evidence from developmental deficits.

This article concerns how the orientations of objects are represented in the human brain. We propose a coordinate-system hypothesis of orientation representation (COR) and show that the hypothesis provides an explicit basis for interpreting orientation errors. Next, we report results from three studies of individuals with developmental deficits in the processing of orientation information, demonstrating that the COR hypothesis can interpret the error patterns in each study. We conclude by discussing several issues concerning the interpretation of our results, the COR hypothesis, and the use of developmental deficits as a basis for inferences about normal cognition.

Neurocognitive function in HIV-infected patients with low weight and weight loss.

OBJECTIVE: To determine neurocognitive function in HIV-infected subjects with low weight and weight loss. DESIGN: Cross-sectional cohort. METHODS: Baseline data from male and female participants in longitudinal treatment studies of AIDS wasting were analyzed. Fifty-seven HIV-infected women (age: 38 +/- 5 years, education level: 12.3 +/- 2.3 years) and 24 HIV-infected men (age: 37 +/- 5 years, education level: 13.5 +/- 2.9 years) with weight <90% IBW or loss of >10% of preillness weight maximum underwent standardized neurocognitive testing to measure intellectual functioning, attention, memory, and fine motor dexterity. The z scores were determined using age- and gender-specific normative data. RESULTS: Among women, IQ (87 +/- 13, z score: -0.8 +/- 0.8 SD) and executive functioning scores (-0.7 +/- 1.2 SD) were below average but within normal limits. In contrast, performance (z scores) on measures of verbal learning (-2.5 +/- 1.5 SD), visuospatial abilities (-2.5 +/- 2.0 SD), and motor coordination (-2.3 +/- 3.3 SD) fell significantly below normal limits. Among men, IQ score was 96 +/- 13 SD (z score: -0.3 +/- 0.8 SD). Performance was below average on measures of verbal learning (-1.0 +/- 1.7 SD) and visual construction (-1.6 +/- 1.7 SD) but within normal limits on executive functioning (-0.1 +/- 1.0 SD). CONCLUSIONS: HIV-infected women at low weight demonstrate significantly reduced verbal learning, memory, and motor function, whereas HIV-infected men at low weight demonstrate more moderate impairment in verbal learning and other measures of neurocognitive function.