Antonieta Nieto

Brain atrophy as a marker of cognitive impairment in mildly disabling relapsing–remitting multiple sclerosis

Background and purpose:  We have studied the relationship between neuropsychological impairment and magnetic resonance imaging (MRI) measures in mildly disabling relapsing–remitting multiple sclerosis (RRMS).

Neuropsychological test performance of patients with Friedreich's ataxia.

Although recognized as one of the most common hereditary diseases of the nervous system, the neuropsychological deficits in Friedreichs ataxia (FA) have rarely been studied. A protocol was constructed to assess the major cognitive areas in patients with FA and pair-matched normal controls. Motor difficulties, dysarthria and fatigability were taken into account. Neuropsychological assessment showed decreased motor and mental reaction times, reduced verbal span, deficits in letter fluency, impaired acquisition and consolidation of verbal information, proactive interference effect, and alterations in complex visuoperceptual and visuoconstructive abilities, in comparison with the control group. Magnetic resonance images showing cerebellar atrophy in the majority of patients suggest that cerebellar degeneration and the interruption of afferent and efferent cerebellar connections could be related to the cognitive deficits shown by our patients.

Differential impairment in semantic, phonemic, and action fluency performance in Friedreich's ataxia: possible evidence of prefrontal dysfunction.

This study examined phonemic (letters), semantic (animals) and action verbal fluency cues in twenty-four patients with FRDA, and twenty matched healthy control subjects. The Action Fluency Test (AFT) is a newly-developed verbal fluency cue that consists in asking the subject to rapidly generate verbs. Given the high presence of dysarthria and cognitive slowness in FRDA patients, control tasks were administered in order to dissociate motor/articulatory impairment and cognitive slowness from verbal fluency deficit. Results showed that patients and control subjects performed similarly on the semantic fluency task. In contrast, patients performed significantly poorer on phonemic and action fluency tests. Correlational analyses showed that the deficits cannot be attributed to dysarthria or cognitive slowness. Although executive processes are necessary for initiating and monitoring all verbal fluency tasks, phonemic and action fluency may place a greater burden on strategic processes, given that they require a more unusual type of lexicon search. Thus, the deficits found occur in tasks that require greater executive/prefrontal control. This impairment might be the result of an affectation of cerebellum-prefrontal cortex connections, although the possibility of a primary prefrontal dysfunction remains to be investigated.

Cognition in Friedreich Ataxia

Friedreich ataxia (FRDA) is the most frequent of the inherited ataxias. However, very few studies have examined the cognitive status of patients with genetically defined FRDA. Our aim was to study cognitive performance of FRDA patients taking into account the motor problems characteristic of this clinical population. Thirty-six FRDA patients were administered a comprehensive neuropsychological battery measuring multiple domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions, and language. Thirty-one gender, age, years of education, and estimated IQ-matched healthy participants served as control subjects. All participants were native Spanish speakers. Patients showed decreased motor and mental speed, problems in conceptual thinking, a diminished verbal fluency, deficits in acquisition of verbal information and use of semantic strategies in retrieval, visuoperceptive and visuoconstructive problems, and poor action naming. Scores on the depression inventory were significantly higher in patients than controls, but depression did not account for group differences in cognitive performance. The observed pattern of neuropsychological impairment is indicative of executive problems and parieto-temporal dysfunction. Neuropathological and neuroimaging studies with FRDA patients have reported only mild anomalies in cerebral hemispheres. Thus, cognitive impairment in FRDA is probably caused by the interruption of the cerebro-cerebellar circuits that have been proposed as the anatomical substrate of the cerebellar involvement in cognition.

Hemispheric asymmetry in lexical decisions : The effects of grammatical class and imageability

It has been suggested that neural systems for lexical processing of nouns and verbs are anatomically distinct. The aim of the present study was to investigate if brain asymmetry for the processing of these two grammatical classes is also different. Neurologically intact adults performed a lateralized lexical decision task with grammatically unambiguous words of high, medium, and low degrees of imagery. For error scores a right visual field (RVF) advantage and an overall effect of imageability were obtained. For latency scores grammatical class and imageability modified visual field differences: in the noun class a RVF advantage was obtained only for low imagery nouns, while for the verbs the RVF advantage was present for both medium and low imagery verbs. These results suggest that the participation of right hemisphere neural systems in the processing of verbs is more limited than in the processing of nouns.

Cognitive decline is mediated by gray matter changes during middle age

The present theoretical framework of Alzheimers disease proposes that pathophysiological changes occur 10-20 years before the diagnosis of dementia. We addressed the question of how age-related changes in gray matter mediate the cognitive performance during middle age. Eighty-two participants (40-50 years, ±2) were assessed with a comprehensive neuropsychological battery covering a broad spectrum of cognitive domains and components. Mediation effects were studied with hierarchical regression and bootstrapping analysis. Results showed that more vulnerable cognitive components were related to executive functioning and in a lesser degree to processing speed. Age-related differences in gray matter mainly involved the frontal lobes. Moreover, age-related differences in visuoconstructive, visuospatial functions, reaction time, and mental flexibility and executive control were mediated by several gray matter regions. It is important to increase the knowledge of the impact of brain changes on cognitive function during middle age. To define the early stages of the aging process may allow early detection of pathologic changes and therapeutic interventions.

Semantic capabilities of the left and right cerebral hemispheres in categorization tasks: Effects of verbal-pictorial presentation

Two lateral tachistoscopic experiments were carried out to test semantic capabilities of the left and right cerebral hemispheres through categorization tasks with verbal and pictorial presentations. RVF advantages were obtained for verbal presentations in both category-membership and category-matching tasks. However, no significant visual-field differences were found for any pictorial presentation. We also found a higher degree of sensitiveness of the positive judgements for the detection of hemispheric differences and sex differences in patterns of functional asymmetries with a greater lateralization in males.

Hemispheric specialization for word classes with visual presentations and lexical decision task

In the present paper we study the possible RH capabilities for the processing of adjectives and verbs of high frequency and medium imagery using a lexical decision task and a horizontal display. In the analysis of both RTs and mean errors, a RVF advantage is obtained. The interaction VF x Word Class did not reach significance. Therefore, we did not find evidence of differences in the visual-field effect for any syntactic class. These results support a LH superiority for the processing of both adjectives and verbs. For the nonword conditions (pseudoverbs and pseudoadjectives), no visual field differences were observed in either group. Methodological aspects are also discussed.

Cognitive decline before the age of 50 can be detected with sensitive cognitive measures

BACKGROUND To define the profile of age-related differences in cognition in healthy middle-aged adults in order to identify the most sensitive measures of early cognitive decline. To study whether these differences precede cognitive decline in the elderly. METHOD 141 cognitively normal participants (101 middle-aged adults with age 40-50±2; and 40 elderly individuals with age 65±2) were assessed with a comprehensive neuropsychological protocol covering processing speed, attention, executive functions, verbal and visual episodic memory, procedural memory, visuoconstructive, visuoperceptive and visuospatial functions, and language. RESULTS Age-related differences were detected before the age of 50 in cognitive reaction time, executive control, initial learning in verbal episodic memory, complex visuoconstructive and visuospatial functions, and lexical access. These differences preceded more extensive cognitive decline present at the age of 65. CONCLUSIONS Our findings suggest subtle executive dysfunction before the age of 50, together with slowing in processing speed later on in the transition to old age. This profile could be explained by changes in the frontal lobe and its connections, starting at middle-age. These findings, together with future research, may be important for the diagnosis, prognosis, and prevention of pathological aging at a very early level.

Mild cognitive impairment in Parkinson’s disease: Diagnosis and progression to dementia

ABSTRACT Introduction: Mild cognitive impairment is common in nondemented Parkinson disease patients (PD-MCI) and is considered as a risk factor for dementia (PDD). Recently, the Movement Disorder Society (MDS) published guidelines for PD-MCI, although the studies available are still limited. The aim of this work was to characterize PD-MCI and its progression to dementia. Moreover, the study variables could be considered as predictors for the progression of cognitive impairment. Method: The study included 43 patients with idiopathic PD (mean age = 59.19 years, SD = 9.64) and 20 healthy and neurologically normal controls (mean age = 60.85 years, SD = 12.26). The criteria proposed by the MDS Task Force were applied for the PD-MCI diagnosis. Follow-up assessments were conducted within six to eight years after the diagnosis of PD-MCI. Results: The results showed that 60.5% of the patients were diagnosed with PD-MCI when a comprehensive assessment was performed (MDS criteria Level 2), while 23.3% of the patients met MCI criteria when a brief assessment was used (MDS criteria Level 1). Multiple domain impairment was the most frequent impairment (96.2%). A total of 42.3% of PD-MCI patients had dementia in the follow-up study. Logistic regression showed that the Hoehn and Yahr stage and education significantly contributed to the prediction of PD-MCI. Moreover, the Hoehn and Yahr stage and memory domain significantly contributed to the prediction of dementia. Conclusions: The results of the study: (a) provide relevant data about the process of validation of the MDS PD-MCI criteria, (b) reinforce the hypothesis that PD-MCI is more frequent than previous studies showed without applying MDS criteria, and (c) confirm that PD-MCI is a risk factor for the onset of dementia. Finally, the study shows that neurological impairment, educational level and memory impairment were predictors for the progression of cognitive impairment.