Alzheimer Disease: Bonnefoy M

Krolak-Salmon P, Seguin J, Perret-Liaudet A, Desestret V, Vighetto A, Bonnefoy M. · Service de médecine gériatrique, centre hospitalier Lyon-Sud, hospices civils de Lyon, Pierre-Bénite cedex, France. · Rev Med Interne. · Pubmed #18584921 No free full text.

Abstract: PURPOSE: To review the current concepts in the biological diagnosis of Alzheimer's disease (AD) and related disorders. CURRENT KNOWLEDGE AND KEY POINTS: As new therapeutics specific of AD may be available soon, early diagnosis of AD in the context of mild cognitive impairment (MCI) or dementia appears to be challenging. The high amount of atypical clinical forms of AD leads to develop new tools allowing in vivo diagnosis. New CerebroSpinal Fluid (CSF) biomarkers seem to reflect specific aspects of deep neuropathological changes observed in AD, i.e. amyloid deposits and neurofibrillary tangles. Amyloid beta-peptide 1-42 (Abeta(1-42)) and hyperphosphorylated tubulin associated unit (tau) isoforms appear to be the most sensitive and specific CSF biomarkers, the combination of these biomarkers depicting the best diagnosis value for AD. These molecules are also efficient in the prediction of the conversion from the MCI state to the dementia state of AD. Combined to clinical and neuro-imaging information, CSF biomarkers appear thus to be highly relevant in improving the early etiological diagnosis of dementia. FUTURE PROSPECTS AND PROJECTS: The current research focalises on the development of new molecules coming from Abeta and tau protein families, in the CSF and in the serum, as well as molecules reflecting other pathological metabolism changes, as alpha-synuclein in Lewy Body Disease. The diagnosis value of CSF biological markers is so promising that they have been recently included in the research diagnosis criteria of AD.

Petitot C, Perrot X, Collet L, Bonnefoy M. · Service de médecine gériatrique, Centre hospitalier Lyon-Sud. · Psychol Neuropsychiatr Vieil. · Pubmed #17556218 No free full text.

Abstract: Alzheimer's disease has major social and family consequences. However, therapeutic strategies are still limited. Non-pharmacological therapeutic approaches are known to be useful to protect the intellectual abilities of the patients, or at least, to slow down their decline. Therefore, it is important to pay attention to the consequences of sensory impairment in these old patients. Indeed, sensory troubles, mainly concerning hearing, may have an impact on the cognitive and behavioral symptoms. Several studies showed that the management of hearing impairment could afford cognitive and behavioral benefits in demented subjects as well as for the non-demented people. These results are encouraging, and suggest that hearing management should be applied to all hearing impaired patients with Alzheimer's disease.

Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M, Dartigues JF, de Groot L, Ferry M, Galan P, Hercberg S, Jeandel C, Morris MC, Nourhashemi F, Payette H, Poulain JP, Portet F, Roussel AM, Ritz P, Rolland Y, Vellas B. · Service de Medecine Interne et de Gerontologie Clinique, Pavillon J.P. Junod, Centre Hospitalier Universitaire La Grave-Casselardit, Toulouse cedex 9, France. · J Nutr Health Aging. · Pubmed #17435956 No free full text.

Abstract: Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta analyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.

Gillette Guyonnet S, Abellan Van Kan G, Alix E, Andrieu S, Belmin J, Berrut G, Bonnefoy M, Brocker P, Constans T, Ferry M, Ghisolfi-Marque A, Girard L, Gonthier R, Guerin O, Hervy MP, Jouanny P, Laurain MC, Lechowski L, Nourhashemi F, Raynaud-Simon A, Ritz P, Roche J, Rolland Y, Salva T, Vellas B, Anonymous00256. · No affiliation provided · J Nutr Health Aging. · Pubmed #17315079 No free full text.

Abstract: Weight loss, together with psychological and behavioural symptoms and problems of mobility, is one of the principal manifestations of Alzheimer's disease (AD). Weight loss may be associated with protein and energy malnutrition leading to severe complications (alteration of the immune system, muscular atrophy, loss of independence). Various explanations have been proposed such as atrophy of the mesial temporal cortex, biological disturbances, or feeding behaviours; however, none has been proven. Prevention of weight loss in AD is a major issue. It requires regular follow-up and must be an integral part of the care plan. The aim of this article is to review the present state of scientific knowledge on weight loss associated with AD. We will consider four points: the natural history of weight loss, its known etiological factors, its consequences and the various management options.

Bonnefoy M, Drai J, Kostka T. · Service de médecine gériatrique, Pavillon Michel Perret. CH. Lyon-Sud, 69495 Pierre-Bénite. · Presse Med. · Pubmed #12192730 No free full text.

Abstract: FREE RADICALS AND THE THEORY OF AGING: Severe oxidative stress progressively leads to cell dysfunction and ultimately cell death. Oxidative stress is defined as an imbalance between pro-oxidants and/or free radicals on the one hand, and anti-oxidizing systems on the other. The oxygen required for living may indirectly be responsible for negative effects; these deleterious effects are due to the production of free radicals, which are toxic for the cells (superoxide anions, hydroxyl radicals, peroxyl radicals, hydrogen peroxide, hydroperoxides and peroxinitrite anions). Free radical attacks are responsible for cell damage and the targeted cells are represented by the cell membranes, which are particularly rich in unsaturated fatty acids, sensitive to oxidation reactions; DNA is also the target of severe attacks by these reactive oxygen species (ROS). THE DEFENCE SYSTEMS: These are represented by the enzymes and free radical captors. The latter are readily oxidizable composites. The free radical captor or neutralization systems of these ROS use a collection of mechanisms, vitamins (E and C), enzymes [superoxide dismutase (SOD), glutathion peroxidase (GPx) and others], and glutathion reductase (GSH), capable of neutralizing peroxinitrite. The efficacy of this system is dependent on the genome for the enzymatic defence systems, and on nutrition for the vitamins. Some strategies aimed at reducing oxidative stress-related alterations have been performed in animals. However, only a few can be used and are efficient in humans, such as avoidance of unfavourable environmental conditions (radiation, dietary carcinogens, smoking...) and antioxidant dietary supplementation. DIETARY SUPPLEMENTATION: Epidemiological data suggest that antioxidants may have a beneficial effect on many age-related diseases: atherosclerosis, cancer, some neurodegenerative and ocular diseases. However, the widespread use of supplements is hampered by several factors: the lack of prospective and controlled studies; insufficient knowledge on the pro-oxidant, oxidant and ant-oxidant properties of the various supplements; growing evidence that free radicals are not only by-products, but also play an important role in cell signal transduction, apoptosis and infection control. RECOMMENDATIONS: Although current data indicate that antioxidants cannot prolong maximal life span, the beneficial impact of antioxidants on various age-related degenerative diseases may forecast an improvement in life span and enhance quality of life. The current lack of sufficient data does not permit the systematic recommendation of anti-oxidants. Nevertheless, antioxidant-rich diets with fruit and vegetables should be recommended.

Bediou B, Ryff I, Mercier B, Milliery M, Hénaff MA, D'Amato T, Bonnefoy M, Vighetto A, Krolak-Salmon P. · Université de Lyon, Service de Neurologie, Centre Hospitalier Lyon Sud, Lyon, F-69003, France. · J Geriatr Psychiatry Neurol. · Pubmed #19321881 No free full text.

Abstract: Abnormal decoding of social information has been associated with the conversion from prodromal Alzheimer's disease (AD) to dementia. Since the distributed neural networks involved in face processing are differentially affected in prodromal and dementia states of AD and in Fronto-Temporal Dementia (FTD), we hypothesized a differential impairment in face processing in these populations. Facial expression, gender and gaze direction decoding abilities were examined in patients with probable amnesic Mild Cognitive Impairment (aMCI, N=10) fulfilling criteria for prodromal AD, in patients with mild and moderate AD (N=10) as well as in FTD patients (N=10) and in a group of age- and sex-matched healthy comparison subjects (N=10). Gender recognition was preserved in all groups. Compared to controls, patients with mild or moderate AD were impaired in expression recognition and FTD patients were impaired in expression and gaze direction determination, whereas MCI patients were not impaired at all.

Tarroun A, Bonnefoy M, Bouffard-Vercelli J, Gedeon C, Vallee B, Cotton F. · MRI Center, Lyon Sud Hospital, 69495, Pierre Benite, France. · Surg Radiol Anat. · Pubmed #17119857 No free full text.

Abstract: Although mild progressive specific structural brain changes are commonly associated with normal human aging, it is unclear whether automatic or manual measurements of these structures can differentiate normal brain aging in elderly persons from patients suffering from cognitive impairment. The objective of this study was primarily to define, with a standard high resolution MRI, the range of normal linear age-specific values for the hippocampal formation (HF), and secondarily to differentiate hippocampal atrophy in normal aging from that occurring in Alzheimer disease (AD). Two MRI-based linear measurements of the hippocampal formation at the level of the head and of the tail, standardized by the cranial dimensions, were obtained from coronal and sagittal T1-weighted MR images in 25 normal elderly subjects, and 26 patients with AD. In this study, dimensions of the HF have been standardized and they revealed normal distributions for each side and each sex: the width of the hippocampal head at the level of the amygdala was 16.42 +/- 1.9 mm, and its height 7.93 +/- 1.4 mm; the width of the tail at the level of the cerebral aqueduct was 8.54 +/- 1.2 mm, and the height 5.74 +/- 0.4 mm. There were no significant differences in standardized dimensions of the HF between sides, sexes, or in comparison to head dimensions in the two groups. In addition, the median inter-observer agreement index was 93%. In contrast, the dimensions of the hippocampal formation decreased gradually with increasing age, owing to physiological atrophy, but this atrophy is more significant in the group of AD.