Biomedical subjects

Dina Zekry

Publications and source records attributed to Dina Zekry.

9 recordsLinked to original sources

PubMed2005

[The economical impact of dementia].

An epidemiology closely linked with the increase in life span. In most countries, the prevalence of dementia varies between 6 and 8% for individuals aged 65 years or more. It then dramatically increases with each subsequent decade, reaching around 30% of the population aged over 85. The costs associated with dementia are correlated with the increase in age and are of increasing concern for politicians, healthcare professionals and family members of demented patients. Current estimations are approximate, but dementia appears to be the most costly disease for society after the age of 65 years in France, the Netherlands, Sweden, or the United States. Detailed cost analyses have distinguished the direct medical,direct non-medical and intangible costs. The most important contribution in costs for society is the long-term care by health care professionals (institutionalization corresponding to 2/3 of the total costs for society!), but the care provided by the helpers and the families is even greater, even though difficult to quantify. The current question is to know whether present and future medical treatments will be able to reduce the tremendous financial costs of this chronic disease.

Activities of Daily Living↗

PubMed2005

[Mixed dementia: a neuropathologic point od view].

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of dementia in the elderly. Although AD can be diagnosed with a very high degree of accuracy, the distinction between pure AD, VaD and mixed dementia (MD), where both pathologies co-exist in the same patient, remains a controversial issue and one of the most difficult diagnostic challenges. MD represents a very frequent pathology, especially in the elderly, as underlined by the neuropathological studies. However, the respective importance of degenerative and vascular lesions, their interaction in the genesis of dementia and the mere existence of mixed dementia are still debated. Accurate diagnosis of MD is of crucial significance for epidemiologic purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure diseases, either AD or VaD, and have provided little data on the best therapeutic approach to MD. This review will provide an overview of neuropathological aspects of MD in the elderly, which appears to be one of the most common forms of dementia.

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PubMed2003

Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia.

Abeta peptide deposits are observed in brain cortical and leptomeningeal microvessels in a few families, in patients with Alzheimer's disease and in cognitively normal elderly subjects. These deposits, which cause Abeta amyloid angiopathy, are usually associated with other lesions induced by Abeta peptide and tau pathologies. To investigate the consequences of cerebral amyloid angiopathy on arterial morphology and search for correlations with the degree of cognitive impairment, we carried out a prospective clinicopathological and morphometric study in 29 institutionalized elderly patients cognitively normal or affected with sporadic dementia associated with Alzheimer-type lesions, cerebral infarcts or both. We measured the external and internal diameters of arteries 40-120 microm wide, containing moderate or severe Abeta deposits, and of unaffected arteries in the temporal and frontal lobes. We found no differences in the mean external diameters. In contrast, the mean internal diameters of vessels with moderate Abeta deposits were smaller than those of unaffected vessels. Conversely, the internal diameters of severely affected vessels were larger than those of unaffected vessels. This suggests that arterial walls become thicker during the early stages of amyloid angiopathy, and the diameter of the lumen decreases, whereas during advanced stages, the walls become thinner and the lumen becomes larger. In addition, we assessed the overall severity of amyloid angiopathy. This showed that thinner arterial walls and the severity of amyloid angiopathy were correlated to dementia. In a multivariate model that integrates the other macroscopic and microscopic lesions that may be implied in the mechanism of cognitive impairment, the severity of amyloid angiopathy per se explained 10% of the variability in the cognitive impairment.

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PubMed2003

A role for NOX NADPH oxidases in Alzheimer's disease and other types of dementia?

Because of population ageing, dementias are likely to become a major scourge of the 21st century. Causes of dementia include Alzheimer's disease, cerebrovascular disease, and lesser known entities such as frontotemporal dementia or dementia with Lewy bodies. Neuroinflammation is likely to play an important role in the pathogenesis of dementia by the killing of neurons through inflammatory mechanisms. Such a role of neuroinflammation is well documented for Alzheimer's disease, and it is likely to play a role in other types of dementia as well. Reactive oxygen species (ROS) play a key role in inflammatory tissue destruction. The phagocyte NADPH oxidase NOX2 is the best studied ROS-generating system. In the central nervous system, it is expressed in microglia and--to a lesser extent--in neurons. Indeed, there is emerging experimental evidence for a role of NOX2 in Alzheimer's and cerebrovascular disease. Recently, six novel ROS-generating NADPH oxidases with homology to NOX2 have been discovered. Several of them are also expressed in the central nervous system. In this article, we hypothesize a role of NOX-type NADPH oxidases in inflammatory neuronal loss. We review presently available evidence and suggest that NOX-type NADPH oxidases may become promising pharmacological targets for the treatment and prevention of dementia.

Alzheimer Disease↗

PubMed2002

Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly.

The relative importance of vascular and Alzheimer's disease (AD) lesions, their interaction in the development of cognitive impairment and the very existence of mixed dementia induced by the potentiation of both mechanisms remain controversial. The aim of this study was to assess whether the patients with infarcts and lacunes have fewer plaques and tangles than those without vascular lesions, for similar severity of clinical dementia. We performed a prospective clinicopathological study in elderly patients of a long-stay care unit. The severity of clinical dementia was assessed by psychometry performed according to standardized methods less than 6 months before death. A volumetric study of cerebral vascular lesions was performed at post-mortem study of the brain. The density of neuritic plaques (SP), Amyloid beta focal deposits (A beta FD), and neurofibrillary tangles (NFT) in the temporal and frontal isocortex was quantified. According to DSM III criteria, 28 of the 33 patients for whom autopsies were performed had dementia. Twenty-four of the included patients had degenerative or vascular lesions, or both. The volume of infarcts and lacunes was significantly correlated with the severity of cognitive impairment. The density of SP, A beta FD and NFT in the temporal and frontal isocortex was significantly lower when vascular lesions were present. For similar clinical severity of dementia, there were fewer AD lesions in patients with vascular lesions than in those without vascular lesions.

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PubMed2002

Alzheimer's disease and brain infarcts in the elderly. Agreement with neuropathology.

Clarifying the etiology of dementia is one of the most difficult diagnostic challenges, especially in the elderly. We examined the accuracy of clinical criteria to distinguish Alzheimer's disease (AD) and dementia associated with infarcts of the brain, either isolated (vascular dementia) or associated with degenerative lesions (mixed dementia). We carried out a prospective clinico-neuropathological study in a selected series of hospitalized patients. We evaluated the clinical aspects of 33 patients aged over 75 years by use of the criteria and scores of DSMIII, NINCDS-ADRDA, Loeb and Gandolfo, ADDTC and NINDS-AIREN and the Hachinski Ischemic Score. The neuropathological diagnosis was considered to be the gold standard. When comparing clinical criteria and neuropathology, the agreement was moderate for Hachinski's score (0.50) and Loeb's score (0.43) and substantial for the ADDTC (0.63) and the NINDS-AIREN (0.67). When mixed dementias were excluded, the agreement between all clinical criteria and scores and the pathological diagnosis rose to 0.88. Hachinski's score was the most sensitive (0.89) and the NINDS-AIREN the most specific (0.86) for the diagnosis of vascular dementia. In conclusion, all sets of clinical criteria distinguished pure AD from vascular dementia with a high accuracy whereas mixed dementia was clinically under-recognized. The NINDS-AIREN criteria were the most discriminating for the accurate identification of patients with mixed dementia.

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PubMed2002

Mixed dementia: epidemiology, diagnosis, and treatment.

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of dementia in older people. Although AD can be diagnosed with a considerable degree of accuracy, the distinction between isolated AD, VaD, and mixed dementia (MD), where both pathologies coexist in the same patient, remains a controversial issue and one of the most difficult diagnostic challenges. Although MD represents a very frequent pathology, especially in older people, as reported in neuropathological studies, the respective importance of degenerative and vascular lesions, their interaction in the genesis of dementia, and the mere existence of MD are still debated. Accurate diagnosis of MD is of crucial significance for epidemiological purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure disease, AD or VaD, and have provided little information on the best therapeutic approach to MD. This article provides an overview of MD in older people. A retrospective review of the recent literature on prevalence, incidence, course, risk factors, diagnosis, and treatment of MD was performed. The article also emphasizes the need for further studies, including neuropsychological and functional evaluations, and neuroimaging and clinicopathological correlations to develop a better understanding of MD, which appears to be one of the most common forms of dementia.

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PubMed2002

End-of-life care of persons with dementia.

Many clinicians with different training and practice are involved in the care of persons with dementia. Whereas neurologists and psychiatrists focus their attention on the early phase of dementia, geriatricians and palliative care specialists are particularly involved at the end of demented patients' lives. To summarize the progress of knowledge in this field, it seems possible to answer four fundamental questions. When? Several longitudinal studies of cohorts of demented and nondemented patients showed clearly that dementia is a risk factor for early death. There are no survival differences between Alzheimer's and Lewy body disease patients. Patients with vascular dementia have the worst prognosis. These results need to be analyzed with consideration of associated comorbidity, types and intensity of care, and dementia treatment. Why? Studies conducted on the basis of death certificates appear to be biased. A large autopsy study performed in the geriatric department of Geneva University Hospital showed no difference existed in immediate causes of death between demented and nondemented hospitalized old patients. On the other hand, cardiac causes are significantly more frequent in vascular dementia than in Alzheimer's disease or mixed dementia patients. How? Deaths of demented patients raise a lot of ethical considerations. It is always difficult to know demented patients' awareness of the end of life. It is really difficult to accompany these patients, with whom communication is essentially nonverbal. During this delicate phase of the end of life, how can formal health professionals help the family members who are afraid of both death and dementia? And after? Suffering of family members and caregivers has to be strongly considered. This goal includes the improvement of our communication skills with the patient, and the facilitation of interdisciplinary exchanges with the caregiver's team and with the family members to allow acceptance of the death.

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PubMedDate not supplied

The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy.

Vascular dementia appears rarer than previously thought, but the contribution of vascular lesions to cognitive impairment in Alzheimer's disease (AD) affected patients (mixed dementias) is now recognized as frequent. The role of strategic areas of the brain involved in the cognitive decline induced by vascular lesions and their relative contributions to the severity of the dementing process remain poorly understood. We determined the relationship between the severity of clinical dementia and the volume of different brain areas affected by infarcts in a prospective clinicopathological study in elderly patients. A volumetric study of the functional zones of Mesulam's human brain map affected by vascular lesions was made and correlations between quantified neuropathological data and the severity of dementia were performed in cases with large vascular lesions only, pure AD, and both lesions. The severity of cognitive impairment was significantly correlated with the total volume of infarcts but in a multi-variate model the volume destroyed in the limbic and heteromodal association areas, including the frontal cortex and in the white matter explained 50% of the variability in MMSE and GDS. The total volume of ischemic lesions explained only 0.1-5% of the variability in MMSE and GDS. Age only explained an extra of 0.1-1.6%. This study confirms that infarcts located in strategic areas have a role in the mechanism of cognitive impairment and brings a key for their quantification. It may be useful for developing neuropathological criteria in multi-infarct and mixed dementias.

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