Emilie Beaufils

Precuneus and Cingulate Cortex Atrophy and Hypometabolism in Patients with Alzheimer’s Disease and Mild Cognitive Impairment: MRI and 18F-FDG PET Quantitative Analysis Using FreeSurfer

Objective. The objective of this study was to compare glucose metabolism and atrophy, in the precuneus and cingulate cortex, in patients with Alzheimers disease (AD) and mild cognitive impairment (MCI), using FreeSurfer. Methods. 47 individuals (17 patients with AD, 17 patients with amnestic MCI, and 13 healthy controls (HC)) were included. MRI and PET images using 18F-FDG (mean injected dose of 185 MBq) were acquired and analyzed using FreeSurfer to define regions of interest in the hippocampus, amygdala, precuneus, and anterior and posterior cingulate cortex. Regional volumes were generated. PET images were registered to the T1-weighted MRI images and regional uptake normalized by cerebellum uptake (SUVr) was measured. Results. Mean posterior cingulate volume was reduced in MCI and AD. SUVr were different between the three groups: mean precuneus SUVr was 1.02 for AD, 1.09 for MCI, and 1.26 for controls (p < 0.05); mean posterior cingulate SUVr was 0.96, 1.06, and 1.22 for AD, MCI, and controls, respectively (p < 0.05). Conclusion. We found graduated hypometabolism in the posterior cingulate cortex and the precuneus in prodromal AD (MCI) and AD, whereas atrophy was not significant. This suggests that the use of 18F-FDG in these two regions could be a neurodegenerative biomarker.

Brain [18F]FDDNP binding and glucose metabolism in advanced elderly healthy subjects and Alzheimer's disease patients.

BACKGROUND Positron emission tomography (PET) imaging of brain amyloid (Aβ) and neurofibrillary tangle (NFT) load is a candidate biomarker of Alzheimers disease (AD). OBJECTIVES To compare brain Aβ and NFT load and glucose metabolism in advanced elderly (70 years and older) patients with AD and healthy controls (HCs) by PET with [18F]FDDNP and [18F]FDG. METHODS Seven AD patients (mean ± SD age 79.3 ± 3.6 y, Mini-Mental State Examination (MMSE) score 22.1 ± 2.5) and eight HCs (mean age ± SD, 75.7 ± 3.9 y; MMSE score 29.0 ± 1.2) underwent PET with [18F]FDDNP and [18F]FDG. RESULTS Global [18F]FDDNP uptake was significantly higher (p < 0.05) in AD patients (1.15 ± 0.04) than in HCs (1.10 ± 0.06), while global brain metabolism was lower in AD patients than in HCs (AD patients 0.96 ± 0.09; HCs 1.13 ± 0.11; p < 0.05). In HCs, brain glucose metabolism was correlated with age for both the global [18F]FDG SUVr and in the parietal and posterior cingulate regions, while no correlation was found between age and [18F]FDDNP uptake. In AD patients, global [18F]FDDNP uptake and uptake in the frontal and anterior cingulate regions of interest were correlated with MMSE score, while no correlation was observed with brain glucose metabolism. CONCLUSION Imaging Aβ load and NFT with [18F]FDDNP can distinguish AD patients from HCs in an advanced elderly population. It seems to be less sensitive than [18F]FDG to the brain changes observed with normal aging, but more sensitive to cognitive decline in advanced elderly AD patients.

Confirmation of the Amyloidogenic Process in Posterior Cortical Atrophy: Value of the Aβ42/Aβ40 Ratio

Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuo-perceptual dysfunction and praxis declines. This syndrome is related to several underlying diseases, including Alzheimers disease (AD), sometimes involving an amyloidogenic process. The aims of the study were to 1) define cerebrospinal fluid (CSF) biomarker profiles in PCA patients compared to AD patients and 2) explore the amyloidogenic process through the Aβ(42)/Aβ(40) ratio in PCA patients to elucidate the underlying disease in vivo. CSF biomarker analysis (t-tau, p-tau, Aβ(42), and Aβ(42)/Aβ(40) ratio) and neuropsychological examination were performed in 22 PCA patients and compared with those of age-matched AD patients. Associated clinical neurological signs were investigated (e.g., extrapyramidal motor signs, myoclonus). CSF biomarker profiles did not differ significantly between the PCA and AD groups; 82% of patients with PCA fulfilled the biological criteria for typical AD with abnormal levels of the three markers and 18% of PCA patients presented atypical CSF profiles. All PCA patients with associated clinical neurological signs presented typical AD CSF profiles. The clinical presentations of these patients were similar to other PCA subjects. The Aβ(42)/Aβ(40) ratio for all PCA patients, including those with atypical CSF profiles, was decreased. Most PCA syndromes were associated with CSF biomarkers suggestive of AD, even in cases with associated clinical neurological signs. The amyloidogenic process was confirmed by the decreased Aβ(42)/Aβ(40) ratio for all patients. This analysis avoids misdiagnosis in the presence of physiologically high or low amyloid peptide production rates and provides information in vivo to improve understanding of the underlying disease in PCA.

Occurrence of eye movement disorders in motor neuron disease

Abstract The diagnosis of amyotrophic lateral sclerosis (ALS) relies on symptoms and signs related to upper and lower motor neuron injury. Preservation of normal ocular motor movements is an important criterion for making this diagnosis as oculomotility pathways are classically spared in ALS. However, some authors report eye disturbances resulting from nuclear and supranuclear ophthalmoplegia in autopsy-proven ALS. Here, we report a case in which eye movement disorders were an early sign associated with a bulbar-onset ALS. The association of progressive ophthalmoplegia, dysexecutive syndrome and automatico-voluntary dissociation of eyelid occlusion suggested a ‘progressive supranuclear palsy variant’ of ALS caused by a disturbance in the descending frontal projections, even though morphological imaging was normal. Motor neuron disease with eye movement disorders must not be considered as a distinct clinical entity and must not exclude a diagnosis of ALS.

Total Protein Level in Cerebrospinal Fluid is Stable in Elderly Adults

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The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using (18)F-AV45: Is Amyloid the Principal Actor in the Disease?

Background: Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimers disease (AD). The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET) between PCA and AD subjects. Methods: We performed 18F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results: The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion: This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution.

Idiopathic Parkinson’s disease phenotype related to C9ORF72 repeat expansions: contribution of the neuropsychological assessment

BackgroundExpanded GGGGCC hexanucleotide repeats in the non-coding region of the C9ORF72 gene was recently identified as being responsible for over 40% of the cases of amyotrophic lateral sclerosis associated with frontotemporal lobar degeneration, in various extrapyramidal syndromes including supranuclear gaze palsy and corticobasal degeneration, and in addition, has been found to be a rare genetic cause of isolated Parkinsonism. To our knowledge, there is no published data concerning the neuropsychological evaluation of patients diagnosed with idiopathic Parkinson’s disease related with C9ORF72 repeat expansions.Case presentationWe report the results of the comprehensive neuropsychological evaluation in a newly described case in the literature (the sixth) of a patient presenting isolated idiopathic Parkinson’s disease associated with C9ORF72 repeat expansions.The decrease in the patient’s prefrontal functions resulted in a slight decrease in global efficiency. These abnormalities did not appear to be different, with respect to the deficit observed and the intensity of the cognitive impairment, from those classically observed in cases of sporadic idiopathic Parkinson’s disease. Our patient also exhibited a significant impairment in visual gnosis.ConclusionsIf confirmed in other patients, visuoperceptive deficits in idiopathic Parkinson’s disease could represent a red flag that should prompt the clinician to perform addition diagnostic procedures. A thorough neuropsychological assessment may prove to be useful for detecting idiopathic Parkinson’s disease in patients who are suspected of having repeat abnormalities of C9ORF72 expansions.

First Manic Episode Revealing Cerebellar Stroke

An 81-year-old man was admitted to the Geriatric Medicine Unit because of a behavioral disorder that had appeared 2 weeks earlier. His past medical history included arterial hypertension, sleep apnea syndrome, and atrial fibrillation. He was currently medicated with warfarin, amiodarone, alfuzosin, omeprazole, and nicardipine. When he was 57 years old, he had presented with depression after he retired from his job. His family described him as a clever and thoughtful individual without any evident cognitive abnormality, and he had never had any manic symptoms. He suddenly exhibited elevated mood, flight of ideas, distractibility, loquacity, decreased sleep, and graphorrhea. He had no spatial or temporal disorientation or language disorder. His physical examination, especially neurological examination, was normal. According to the symptoms, a manic episode was hypothesized. Laboratory testing (blood cell counts, serum electrolytes, liver function) was normal. Thyroid-stimulating hormone level was normal, syphilis serology was negative, and electroencephalogram was normal. A computed tomography scan without contrast revealed a right cerebellar lesion, suggesting an ischemic stroke. Lithium was initiated (400 mg/d). Seven days later, he progressively recovered a stable mood. Brain magnetic resonance imaging (MRI) (Figure 1) showed a right paramedial cerebellar signal abnormality evocative of an ischemic origin.

[Perception of taste and smell in normal and pathological aging: an update].

The physiological and pathological aging on sense organs is widely studied in the visual and hearing modalities. By contrast, taste and smell changes are widely overlooked. These symptoms are rarely evoked in the elderly and often neglected in clinical practice. Studies in this population are rare and show contradictory results. In this update, we describe the perception of taste and smell in aging. In a first part, we present studies about the aging of smell and taste senses. While taste is remarkably spared during aging, olfaction decreases dramatically since 5th decade of life, frequently resulting in anosmia after 90 years. Numerous causes are evoked: acute conditions (mouth health, medications…) and chronic diseases frequently observed during aging (Alzheimer or Parkinsons diseases) may be responsible of such decline. In the last part, we approach the consequences on geriatric practice, as regards the nutrition of old subjects, including a cognitive approach regarding to perceptual functions and environmental determinants of nutrition. Taste and olfaction disorders should be considered as a geriatric syndrome that geriatricians have to be aware in clinical practice.

A case report of exhibitionist behaviour revealing unsuspected Huntington's disease: a pitfall in forensic medicine.

We present the case of a patient who was recently convicted for exhibitionism whose clinical assessment suggested undiagnosed Huntingtons disease. We summarise the clinical characteristics, the genetics involved and the diagnostic difficulties which can be encountered. Finally, we discuss the implications of this diagnosis in forensic medicine.