Dina Selma Zekry

Frailty syndrome: a transitional state in a dynamic process.

Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.

Mixed Dementia: Epidemiology, Diagnosis, and Treatment

Alzheimers 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.

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 Alzheimers 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 Alzheimers 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 Alzheimers 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. IUBMB Life, 55: 307‐313, 2003

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 Alzheimers 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 Mesulams 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.

Does dementia predict adverse hospitalization outcomes? A prospective study in aged inpatients

Dementia is often considered a predictor of adverse hospitalization outcomes. However, the relative contributions of dementia and other risk factors remain unclear.

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

Aβ peptide deposits are observed in brain cortical and leptomeningeal microvessels in a few families, in patients with Alzheimers disease and in cognitively normal elderly subjects. These deposits, which cause Aβ amyloid angiopathy, are usually associated with other lesions induced by Aβ 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 μm wide, containing moderate or severe Aβ 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 Aβ 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.

Arterial Spin Labeling May Contribute to the Prediction of Cognitive Deterioration in Healthy Elderly Individuals

PURPOSE To explore whether arterial spin labeling (ASL) imaging in cognitively intact elderly individuals may be used to predict subsequent early neuropsychological decline. MATERIALS AND METHODS The local ethics committee approved this prospective study, and written informed consent was obtained from all participants. A total of 148 consecutive control subjects were included, 75 of whom had stable cognitive function (sCON) (mean age, 75.9 years ± 3.4 [standard deviation]; 43 female) and 73 of whom had deteriorated cognitive function (dCON) at 18-month clinical follow-up (mean age, 76.8 years ± 4.1; 44 female). An additional 65 patients with mild cognitive impairment (MCI) (mean age, 76.2 years ± 6.1; 25 female) were also included. Two-dimensional pulsed ASL was performed at the baseline visit. Statistical analysis included whole-brain voxelwise analysis of the ASL relative cerebral blood flow (CBF) data, receiver operating characteristic (ROC) curve analysis of the posterior cingulate cortex (PCC), and voxel-based morphometry analysis of gray matter. RESULTS The voxelwise comparison of ASL revealed decreased relative CBF in the dCON group compared with that in the sCON group and slightly more pronounced relative CBF in the MCI group compared with that in the sCON group, most notably in the PCC (P < .05 corrected). Comparison of the dCON group with the MCI group revealed no significant differences. ROC analysis of relative CBF in the PCC enabled discrimination of dCON (P < .001; area under the ROC curve, 0.66). There was no confounding focal gray matter atrophy. CONCLUSION Reduced ASL in the PCC at baseline is associated with the development of subsequent subtle neuropsychological deficits in healthy elderly control subjects. At a group level, ASL patterns in subjects with dCON are similar to those in patients with MCI at baseline, indicating that these subjects may initially maintain their cognitive status via mobilization of their neurocognitive reserve at baseline; however, they are likely to develop subsequent subtle cognitive deficits.

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

Abstract. 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 Alzheimers 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 Hachinskis score (0.50) and Loebs 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. Hachinskis 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.

Efficiency and applicability of comprehensive geriatric assessment in the Emergency Department: a systematic review

Background and aims: Comprehensive geriatric assessment (CGA) may benefit frail or chronically ill patients in the emergency department (ED), but take too much time to be performed routinely in ED. An alternative approach is to use first a screening tool to detect high-risk patients and then perform CGA in these patients only. This systematic review focuses on the use and value of CGA in ED for evaluation of older patients and its influence on adverse outcomes. This approach is compared with an alternative one using existing screening tools, validated in ED, to detect high-risk patients needing subsequent CGA. This review ends by suggesting a short assessment of CGA to be used in ED and ways to improve home discharge management from ED. Methods: A systematic English Medline literature search was conducted in December 2009, with no date limit with the following Medical Subject Heading (MeSH) terms: “Frail Elderly”, “Health Services for Aged”, “Community Health Nursing”, “Emergency Service, Hospital”, “Geriatric Assessment”, “Patient Discharge”, “Risk Assessment” and “Triage”. Results: We selected 8 studies on CGA efficiency and 14 on screening tools. CGA in ED is efficient for decreasing functional decline, ED readmission and possibly nursing home admission in high-risk patients. As CGA takes too much time to be performed routinely in ED, validated screening tools can be applied to detect high-risk patients who will benefit most from CGA. Conclusions: The selected studies demonstrated that screening of high-risk patients is more efficient than age-based screening, and that CGA performed in ED, followed by appropriate interventions, improves outcomes.

Geriatrics index of comorbidity was the most accurate predictor of death in geriatric hospital among six comorbidity scores.

OBJECTIVES To compare the abilities of six validated comorbidity indices (Charlson index, cumulative illness rating scale [CIRS], index of coexistent diseases, Kaplan scale, geriatrics index of comorbidity [GIC], and chronic disease score) to predict adverse hospitalization outcomes (death during hospitalization, length of stay, and institutionalization). STUDY DESIGN AND SETTING Prospective cohort of 444 elderly inpatients (mean age 85.3) was randomly selected from Geneva geriatric hospital. RESULTS In univariate analyses, GIC was the best predictor for all outcomes. The risk of death was 30 times higher and the risk of prolonged hospitalization and being institutionalized was eight to nine times higher in patients with scores of class 3 or 4. In adjusted logistic regression models, GIC remained the best predictor of death during hospitalization. Higher GIC scores accounted for 25% of the variance of this outcome, with mortality rates differing by a factor of four between the highest and the lowest scores. CIRS was a strong predictor of a prolonged hospital stay and institutionalization, accounting for 10% of the variance of these outcomes. CONCLUSION GIC was the most accurate predictor of death during hospitalization. CIRS could be used to select elderly patients at admission as an indicator of improvement at discharge.