Teresa Moreno-Ramos

Retinal Nerve Fiber Layer Thinning in Dementia Associated with Parkinson's Disease, Dementia with Lewy Bodies, and Alzheimer's Disease

Optical coherence tomography is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL). Previous studies have shown that degenerative changes occur in optic nerve fibers and are manifested as thinning of RNLF in patients with Alzheimers disease (AD). However, there are no studies on the thickness of the RNLF in other types of dementia, such as dementia with Lewy bodies and dementia associated with Parkinsons disease. In this study, patients fulfilling diagnostic for AD (n = 10), dementia with Lewy bodies (n = 10), dementia associated with Parkinsons disease (n = 10), and cognitively normal age-matched controls (n = 10) underwent optical coherence tomography examinations to measure RNLF thickness. There was a significant decrease in RNLF thickness in each type of dementia compared to the control group (Mann-Whitney test, all p < 0.001). Although patients with dementia with Lewy bodies may have a greater thinning than both patients with AD and dementia associated with Parkinsons disease, the differences were statistically nonsignificant (Kruskal-Wallis test, p = 0.525). The thickness of the RNLF correlated significantly (p < 0.001) with both the Mini-Mental State Examination and the Mattis Dementia Rating Scale scores in all types of dementia; that is to say, the greater the cognitive deterioration, the greater the reduction of thickness of the RNLF. The findings from this study show that retinal involvement measured by optical coherence tomography may also be present in non-AD dementias.

Mirrored-self misidentification in a patient without dementia: evidence for right hemispheric and bifrontal damage

Mirrored-self misidentification, often referred as the ‘mirror sign’, is a delusion characterized by the inability to recognize ones own reflected image, often associated with the intact capacity to recognize others in the mirror. It has been described mainly in moderate or severe dementia, especially Alzheimers disease. In the few reported cases without global cognitive impairment, right hemispheric and frontal dysfunctions have been described. We report a 90-year-old man with abrupt onset of the mirror sign after a minor right hemispheric ischemic stroke. Neuropsychological testing revealed preserved cognitive capacities, except for mild to moderate impairment of visuospatial skills, suggesting right hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal infarct, and bifrontal encephalomalacia, consistent with a past history of head trauma. Scattered ischemic white matter lesions in posterior periventricular regions were also seen. It seems that the mirror sign is a multifactorial phenomenon that usually requires right hemispheric dysfunction (perceptual abnormalities, loss of familiarity) and frontal damage (loss of judgement and inability to correct wrong beliefs). The right frontal dorsolateral prefrontal cortex seems to have a crucial role in self-recognition.

Validación de la versión española del test Addenbrooke's Cognitive Examination III para el diagnóstico de demencia

INTRODUCTION Addenbrookes Cognitive Examination is a screening test used to diagnose dementia. The third edition of this test (ACE-III) was recently developed. The aim of this study was to translate and validate the ACE-III in Spanish. METHODS The ACE-III was translated and adapted to Spanish. It was then administered to a group of healthy subjects as well as a group of patients with different types of mild dementia treated in 2 hospitals in Spain. RESULTS Internal reliability (Cronbachs alpha = 0.927), inter-rater reliability (intraclass correlation coefficient = 0.976) and test-retest reliability (kappa 0.995) were excellent. Age (r = -0.512) and education (r = 0.659) showed a significant correlation with total test scores. The diagnostic accuracy of ACE-III was higher than that of the Mini-Mental State Examination, particularly for the group with the highest educational level. Researchers obtained normative data and cut-off points for the diagnosis of dementia. CONCLUSIONS The Spanish version of the ACE-III is a reliable and valid test for diagnosing dementia. Its diagnostic accuracy is high, especially in patients with a higher level of education.

Amyloid Proteins and Their Role in Multiple Sclerosis. Considerations in the Use of Amyloid-PeT imaging

Thioflavin T derivatives are used in positron-emission tomography (PET) studies to detect amyloid protein deposits in patients with Alzheimer disease. These tracers bind extensively to white matter, which suggests that they may be useful in studies of multiple sclerosis (MS), and that proteins resulting from proteolytic processing of the amyloid precursor protein (APP) may contribute to MS. This article reviews data from both clinical and preclinical studies addressing the role of these proteins, whether they are detected in CSF studies or using PET imaging. APP is widely expressed in demyelinated axons and may have a protective effect in MS and in experimental allergic encephalomyelitis in animals. Several mechanisms associated with this increased expression may affect the degree of remyelination in MS. Amyloid-PET imaging may help determine the degree of demyelination and provide information on the molecular changes linked to APP proteolytic processing experienced by patients with MS.

Evaluation of the new consensus criteria for the diagnosis of primary progressive aphasia using fluorodeoxyglucose positron emission tomography.

Background: New consensus criteria have been proposed to classify primary progressive aphasia (PPA) into three variants: agrammatic, semantic, and logopenic. Some studies have subsequently addressed the usefulness of these criteria, with controversial results. We aimed to determine the correlation between the clinical diagnosis according to the new criteria and brain topography in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Patients meeting the PPA criteria were prospectively recruited in a single center during a period of 18 months. They were clinically classified according to the new criteria and underwent FDG-PET. The cerebral metabolism of each patient was compared to a healthy control group using statistical parametric mapping. The expected variant according to the analysis of PET imaging was compared with the clinical diagnosis using the consensus criteria. Results: 32 patients were included. 90% of them fulfilled the consensus criteria and could be classified into one of the three clinical variants. The correlation with the cerebral metabolism was high: the kappa index was 0.91 in the agrammatic variant, 0.71 in the semantic variant, and 0.74 in the logopenic variant. Conclusions: A high correlation with the diagnosis obtained using FDG-PET was found. However, an overdiagnosis of the logopenic variant was observed. These results support the use of the new criteria, but some modifications or complementary studies may still be necessary.

Normative Data for the Spanish Version of the Addenbrooke's Cognitive Examination III

Background: Addenbrookes Cognitive Examination III (ACE-III) is a cognitive test that has been validated for the diagnosis of cognitive disorders. The aim of this study was to provide normative data for the ACE-III for age, education and gender. Methods: The Spanish version of the ACE-III was administered to a group of 273 healthy subjects in a multicenter study in Spain. Correlation and determination coefficients for age, education and gender were estimated. The overlapping interval strategy and linear regression analyses were used to provide adjusted norms for demographic factors and to explore the potential influence of these factors in the performance of the test. Results: Age and education correlated significantly with the total score and with all the domains. Gender correlated only with the domains of attention and visuospatial skills. Norms for the total score and for cognitive domains (attention, memory, fluency, language, and visuospatial skills) are provided. Conclusion: This study confirms the influence of demographic factors (especially age and education) on the performance in the ACE-III and provides normative data for the Spanish version of the ACE-III.

Demencia frontotemporal variante conductual: biomarcadores, una aproximación a la enfermedad

INTRODUCTION Lobar frontotemporal degeneration (FTLD) encompasses a group of molecular disease defined by the deposition of an abnormal protein in the central nervous system. Behavioural variant frontotemporal dementia (bvFTD) is the most frequent clinical presentation of FTLD. The past two decades of research have contributed to a better understanding of this entity, which may be the first manifestation in many different neurodegenerative disorders. DEVELOPMENT We reviewed correlations between clinical, pathological, and genetic findings and the main disease biomarkers of FTLD, with particular interest in bvFTD. Anatomical pathology findings in FTLD are heterogeneous and the syndrome is not associated with any one specific histopathological type. Promising available biomarkers include structural and functional neuroimaging techniques and biochemical and genetic biomarkers. Disease-modifying drugs designed for specific molecular targets that are implicated in FTLD pathogenesis are being developed. CONCLUSIONS BvFTD is a frequent cause of dementia. Of all the clinical variants of FTLD, behavioural variant is the one in which establishing a correlation between clinical and pathological signs is the most problematic. A biomarker evaluation may help predict the underlying pathology; this approach, in conjunction with the development of disease-modifying drugs, offers new therapeutic possibilities.

The Hayling Test: Development and Normalization of the Spanish Version

OBJECTIVE The Hayling Sentence Completion Test evaluates the ability to inhibit an automatic response. It has also been suggested for the assessment of orbitofrontal cortex function. The aim of the study was to develop a Spanish version of the Hayling test and to obtain normative data. METHOD Responses to 60 sentences from 50 healthy controls were used to develop the task. Additionally, 185 healthy controls aged between 18 and 99 years were examined with the test in order to obtain normative data. The overlapping interval strategy was used to maximize the sample size. Age- and education-adjusted scores were obtained using linear regression analysis. RESULTS Age and educational level had a significant effect on the different scores. Good internal reliability and inter-rater variability were observed. CONCLUSIONS We provide normative data adjusted for age and education. Our results enable the use of this test for clinical and research purposes in the field of neuropsychological assessment.

Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease

Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18F fluorodeoxyglucose (FDG‐PET).

Demencia frontotemporal variante conductual: aproximación clínica y terapéutica

INTRODUCTION Behavioural variant frontotemporal dementia (bvFTD) is the most frequent presentation in the clinical spectrum of frontotemporal dementia (FTD) and it is characterised by progressive changes in personality and conduct. Major breakthroughs in molecular biology and genetics made during the last two decades have lent us a better understanding of this syndrome, which may be the first manifestation in many different neurodegenerative diseases. DEVELOPMENT We reviewed the main epidemiological, clinical, diagnostic and therapeutic aspects of bvFTD. Most cases manifest sporadically and the average age of onset is 58 years. Current criteria for bvFTD propose three levels of diagnostic certainty: possible, probable, and definite. Clinical diagnosis is based on a detailed medical history provided by family members and caregivers, in conjunction with neuropsychological testing. Treatments which have been used in bvFDT to date are all symptomatic and their effectiveness is debatable. New drugs designed for specific molecular targets that are implicated in frontotemporal lobar degeneration are being developed. CONCLUSIONS BvFDT is a frequent cause of dementia. It is a non-specific syndrome associated with heterogeneous histopathological and biomolecular findings. The definition of clinical subtypes complemented by biomarker identification may help predict the underlying pathology. This knowledge, along with the development of drugs designed for molecular targets, will offer new treatment possibilities.