Joël Belmin

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

Abstract. The relative importance of vascular and Alzheimers 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 6xa0months 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 β focal deposits (Aβ 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, Aβ 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.

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.

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.

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.

Osler's maneuver: Absence of usefulness for the detection of pseudohypertension in an elderly population

PURPOSEnTo investigate the prevalence and clinical relevance of Oslers maneuver for detecting pseudohypertension in the elderly.nnnPATIENTS AND METHODSnOslers maneuver was performed by one investigator in 205 consecutive inpatients of a French geriatric hospital (40 men and 165 women; mean age 84.2 +/- 6.2 years). In 12 Osler-positive and 12 Osler-negative patients matched for age, sex, and presence of hypertension, the blood pressure values measured directly at the radial artery were compared to those measured indirectly with a standard mercury sphygmomanometer. Aortic and upper limb pulse wave velocities (PWV) were also measured in these 24 patients.nnnRESULTSnTwenty-three of 205 patients (11%) were Osler-positive. Age, sex ratio, and prevalence of hypertension or other cardiovascular diseases did not differ significantly in Osler-positive and Osler-negative patients. Systolic blood pressure (SBP), measured by standard mercury sphygmomanometer, was significantly greater in Osler-positive than Osler-negative patients (157 +/- 37 versus 132 +/- 28 mm Hg; P < 0.01). Diastolic blood pressure (DBP) did not differ significantly (78 +/- 18 versus 74 +/- 14 mm Hg). Interobserver agreement concerning Oslers sign, studied in 40 patients, was good (kappa = 0.72). In 12 Osler-positive and 12 Osler-negative patients, the mean differences between SBP obtained by cuff-manual indirect blood pressure and direct measurements were -3.71 +/- 22.85 mm Hg and -8.59 +/- 14.40 mm Hg (P = NS). For DBP, these differences were 18.40 +/- 15.72 and 12.01 +/- 5.80 mm Hg (P = NS). The differences between the indirect and direct blood pressure measurements were significantly correlated to upper limb PWV, but not aortic PWV, for both SBP and DBP. Pseudohypertension, defined as the indirect measurement overestimation of SBP or DBP by 10 mm Hg or more, was found in 15 of the 24 patients (63%). In these patients, upper limb PWV was significantly greater than in those with no pseudohypertension (7.0 +/- 2.2 versus 5.4 +/- 1.3 m/s; P < 0.05).nnnCONCLUSIONnThe Osler-positive maneuver is frequently found in elderly hospital inpatients, but its ability to detect pseudohypertension in clinical practice is poor. Measurement of upper limb PWV might be a more appropriate way of screening for this condition.

French healthcare workers in geriatric healthcare settings staunchly opposed to influenza vaccination: the VESTA study.

The observational diagnosis phase of the VESTA study was aimed to determine the composite profiles of vaccinated/non-vaccinated HCWs by analyzing reasons to accept/decline influenza vaccination. Between June and September 2005, 2485 HCWs (female: 82.9%; nursing auxiliaries: 42.1%; vaccination coverage: 23.4%) from 53 French geriatric HCSs were included in the study. Cluster analysis determined 3 composite profiles: HCWs for whom information programs on vaccination can be useful (59%), HCWs staunchly opposed to vaccination (36%), and skeptical HCWs (5%). Qualitative analysis provided some aspects of influenza vaccine reluctance. Effective programs would be multidimensional and target the most susceptible group.

Effect of two French nurses' strikes on mortality in a geriatric hospital

PURPOSEnTo study the influence of the 1988 French nurses strikes on mortality in a geriatric hospital.nnnMATERIALS AND METHODSnTwo nurses strikes affected the Charles Foix Hospital near Paris from June 29 to July 31 and from September 17 to October 22, 1988. Mortality was studied in nine geriatric wards of this hospital, including two rehabilitation units comprising 187 beds, and seven long-term care units comprising 1,132 beds. Monthly mortality rates were calculated from the hospitals administrative registers and expressed as deaths per 1,000 patient-days. These rates were calculated in each of the aforementioned nine units for the 36 months preceding the first strike (control period) and for the 12 months following it (study period).nnnRESULTSnOver the control period, monthly mortality was significantly higher in rehabilitation units than in long-term care units (2.46 +/- 1.21 versus 0.83 +/- 0.47, p less than 0.001), but mortality rates among rehabilitation units, as well as among long-term care units, were comparable. Also, during the control period, large seasonal fluctuations in monthly mortality rates were observed in both rehabilitation units and long-term care units (peak in winter and nadir in summer). These rates tended to decrease from year to year in rehabilitation units but not in long-term care units. A statistical model based on time-series analysis of the control period data was used to calculate the expected monthly mortality rates for the study period in rehabilitation units and in long-term care units, respectively. Three of the 12 actual monthly mortality rates exceeded the upper limit of the 95% confidence interval of the 12 expected monthly mortality rates, in the units where the more severe care disruption occurred. A detailed analysis of discharge summaries of these units failed to identify a possible link between some of these deaths and a possible absence of care.nnnCONCLUSIONSnThe nurses strikes did not induce a clear-cut increase in mortality in this population of elderly patients. However, we cannot exclude the possibility that these strikes had some negative effects on health. Our results fail to provide answers to the difficult ethical problems created by such stoppages.