The added value of MRI measures of atrophy in the diagnosis of AD.
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Biomedical subjects
Publications and source records attributed to A Bianchetti.
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Fibroblasts from Alzheimer's disease (AD) patients displayed decreased cytochrome c oxidase (complex IV) activity (P < 0.05). The basal oxygen consumption rate (QO2) and the response to an uncoupler of oxidative phosphorylation did not differ between AD and control fibroblasts. The QO2 of AD fibroblasts was more susceptible (P < 0.05) to inhibition by azide in the range 0.5-5 mM. The basal intracellular pH (pHi) in AD fibroblasts was significantly more acidic than in control ones. The results support the hypothesis that subtle dysfunctions of oxidative energy-producing processes are present in fibroblasts from sporadic AD patients. The alterations observed scantly influence the fibroblasts functioning even in stressful conditions; however in tissues, such as the brain, that rely heavily on oxidative metabolism for their function, similar alterations may trigger molecular mechanisms leading to cell damage.
The present study investigates the influence of energy related metabolic stress on amyloid precursor protein (APP) non-amyloidogenic secretory processing in COS cells. The effect of glucose deprivation on soluble APP (sAPP) secretion has been evaluated: incubation of COS cells with 50 mM 2-deoxy-D-glucose (2-DG) in glucose free medium was able to reduce sAPP secretion (-26%). Sodium azide (NaN3), an inhibitor of cytochrome c oxidase (complex IV of the mitochondrial electron transfer chain) decreased sAPP release in a concentration dependent way (maximum -75%). Treatment of COS cells with the antioxidant glutathione (GSH) fully antagonized the inhibitory effect of azide (1 mM) and elicited sAPP release over basal level. These results suggest that the inhibition of energy metabolism can influence APP processing leading to a decreased secretion of non-amyloidogenic fragments of APP.
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Interleukin 2 (IL-2) is a cytokine produced by activated T cells that plays a crucial role in the immune response and exerts multiple functions in different tissues including the nervous system. The present study was carried out to investigate the effect of recombinant human IL-2 (rhIL-2) on the survival of differnet glial cells type and of cortical neurons in culture. The results demonstrate that rhIL-2 is selectively cytotoxic to oligodendrocytes only if preincubated in aqueous solution (1200 U/ml) for at least two days before being added to the culture. Other glial and neuronal cells were unaffected. The cytotoxic effect was temperature- and concentration-dependent occurring only when rhIL-2 was reincubated at 37 degrees C and was dose-dependently neutralized by antibodies raised against IL-2 indicating that an immunoreactive IL-2 like compound is the active principle. Polyacrilamide gel electrophoresis under native (PAGE) and denaturing (SDS-PAGE) conditions and gel filtration analysis of the rhIL-2 incubated solution suggest that rhIL-2 is cytotoxic to oligodendrocytes only after association into soluble high weight molecular aggregates.
A small feasibility study was performed in Italy to evaluate whether the special care unit (SCU) model could minimize behavioral disturbances in demented patients. In a nursing home an area was selected to provide an appropriate environment for individuals with dementia. The physical environment was adapted, and the staff was trained to meet the needs of demented patients. Sixteen residents were transferred from traditional wards to the SCU. Functional status, cognitive performance, behavioral symptoms, and use of psychotropic drugs or physical restraints were assessed before and 6 months after admission to the SCU. Our findings show that transferring demented persons from traditional nursing home wards to an SCU significantly lessens behavioral problems but does not improve functional abilities or cognitive status after a short period of follow-up. Changes in caring strategies (in particular the use of physical restraints) seem to be important in reducing behavioral problems. The regional government of Lombardia (8.5 million inhabitants) decided to open small (20-bed) SCUs in 60 nursing homes (corresponding to 3.5% of the total nursing home beds in our region) and to reserve these units for demented patients with a high level of behavioral disturbances.
We evaluated the floor effect and convergent, discriminant, and known-group validity of the Bedford Alzheimer Nursing Severity scale (BANS-s), a rating scale comprising cognitive and functional items recently developed for grading severe dementia. Ninety-nine demented patients (81 females and 18 males aged 55-100 years) in two nursing homes were assessed with the BANS-s, established cognitive and functional scales [Mini Mental State Examination, the extended version of the Clinical Dementia Rating (CDR), Katz's basic activities of daily living, Tinetti balance and gait, and Crichton scales], a behavioral scale (UCLA Neuropsychiatric Inventory), and indicators of malnutrition (Prognostic Nutritional Index). A relevant proportion (40%) of patients scored close to the floor of all scales except BANS-s and CDR, which showed a more uniform distribution of scores throughout the possible range. Convergent validity of BANS-s with the other cognitive and functional scales was good, with Pearson's r ranging from 0.62 to 0.79. Discriminant validity analysis of BANS-s versus the UCLA Neuropsychiatric Inventory showed that the two scales measure different domains (Pearson's r = 0.36). To test known-group validity, all patients were divided into two groups of different severity as defined by the Prognostic Nutritional Index. BANS-s and CDR were the scales with the best ability to discriminate malnourished from nonmalnourished patients. As a further validity test, the 37 patients reaching the floor on other cognitive and functional scales were divided into two subgroups of different dementia severity as defined by the Tinetti scale. BANS-s but not CDR was able to differentiate the two groups.
An increased prevalence of celiac disease has been reported in neurological disorders of unknown etiology. A large proportion of Alzheimer's cases is still of unexplained etiology. Thirty-three Alzheimer's patients and 24 elderly controls were screened for celiac disease. IgA and IgG antigliadin antibodies were assayed in serum samples with enzyme-linked immunoassay. Confirmation of celiac disease in positive subjects was made by assaying IgA anti-endomysium antibodies by indirect immunofluorescence. Two Alzheimer's patients and 2 controls were positive for antigliadin antibodies (6 versus 8%; NS). None was positive for anti-endomysium antibodies. We conclude that the prevalence of celiac disease in Alzheimer's disease is not higher than in cognitively unimpaired elders, suggesting that the immune changes in celiac disease are unlikely to play a role in Alzheimer's disease.
The study evaluates the efficacy of a procedural memory stimulation programme in mild and mild-moderate Alzheimer's disease (AD). Twenty basic and instrumental activities of daily living have been selected, and divided into two groups, comparable for difficulty. Ten normal elderly subjects (age 68.0 +/- 4.8 years; MMSE score: 28.7 +/- 0.9; education: 7.6 +/- 3.5 years) were asked to perform the two groups of daily activities and the time required to perform the tasks of each group was recorded and used as a reference. Ten mild and mild-moderate AD patients (age 77.2 +/- 5.3 years; MMSE score: 19.8 +/- 3.5; education: 7.3 +/- 4.7 years) without major behavioural disturbances constituted the experimental group. Patients were evaluated in all 20 daily activities and the time employed was recorded at baseline and after a 3-week training (1 h/d, 5 d/week) period. Five patients were trained during the 3 weeks on half of the 20 daily activities and the other five patients were trained on the remainder. This procedure was adopted in order to detect separately the improvement in "trained" and "not trained" activities, allowing to control better the effects of the intervention. The assessment of the functional impact of the training was directly measured, through the variation of time employed to perform tasks before and after training. After 3 weeks of training a significant improvement was observed for the trained activities, from 3.6 to 1.9 standard deviations below the performance of the normal elderly controls (P < 0.05). AD patients improved also in not-trained activities from 3.5 to 2.7 standard deviations below the controls' performance (P < 0.05). The rehabilitation of activities of daily living through developing procedural memory strategies may be effective in mild and mild-moderate AD patients.
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A battery of visual and spatial perception tests (VOSP) has been administered to a sample of 25 mild Alzheimer's disease (AD) patients and 25 age- and education-matched controls in order to assess visuospatial skills in the early phase of the disease. Among visual object perception tests, AD patients were impaired only in the task where they had to name the stimulus (Silhouettes task). The score in this task significantly correlated with the Boston Naming Test score (r = .73; p < 0.0001). The performance on the Object decision task (which does not require naming), figure-ground analysis, and identification of degraded stimuli was unimpaired. Similarly there were no significant differences for any of the spatial perception tests. The results showing that the performances on most measures of visual and spatial perception is unimpaired, indicate that the "early" perceptual processes, as well as the access to structural knowledge, are not defective in early AD. On the other hand, AD patients are impaired at the level of semantic access and name retrieval. The finding of an highly significant correlation among tests requiring visual access to structural and semantic knowledge suggests that a rigid separation between perceptual and semantic mechanisms may be unwarranted.
The present study shows that cultured fibroblasts from sporadic AD patients present: a) reduced (-30%) cytosolic protein kinase C (PKC) activity; b) increased KD of phorbol ester binding (+94%) in cytosolic fractions; c) reduced (-30%) soluble protein kinase C alpha immunoreactivity; d) lower (-27.5%) basal soluble APP secretion and e) reduced soluble APP secretion in response to low phorbol ester concentrations (over threefold difference using 9 nM phorbol-12,13-dibutyrate-PdBu). Since the PKC-stimulated secretion of APP leads to the cleavage of the precursor within the amyloidogenic beta-A4 fragment, the reduced PKC activity in AD patients may lead to accumulation of potentially amyloidogenic or toxic APP fragments. A defect in the secretion of soluble amyloid beta-protein precursor is indeed suggested by literature data on familial AD fibroblasts as well as by the reported results.
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The aim of this study was to compare the performances on each item of the Mini-Mental State Examination (MMSE) of patients with Alzheimer's disease (AD) and multi-infarct dementia (MID). In order to identify the items that could better distinguish the two groups of patients, 70 AD and 31 MID patients matched for disease severity, age, and education were evaluated. The scores of the 101 patients on each of the MMSE items were entered into a principal component factor analysis using varimax rotation, and two main components were derived. Component 1 was probably representative of recently acquired information, whereas component 2 represented educational level. A score summing the items that loaded on component 1 and the recall item was calculated to generate a measure of episodic memory. Performing analysis of variance and covarying for age and education revealed that this score was statistically different in the two groups, with AD patients having lower values. The data suggest that the MMSE may demonstrate a pattern of impairment of memory that differs between AD and MID. Possible explanations of this finding should take into account the different neuroanatomical impairments and the different degrees of motivation, due to depression or attentional deficits, toward external stimuli.
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The value of functional and morphological neuroimaging in the early diagnosis of Alzheimer's disease (AD) is still debated. Described here are cerebral perfusion and linear measures of medial temporal lobe atrophy in 2 monozygotic twins discordant for AD who were investigated with technetium 99m-hexamethylpropy-leneamineoxime single-photon emission tomography (SPET) and magnetic resonance (MR) imaging. Both showed pathological cortical perfusion findings on SPET, while medical temporal lobe atrophy was present only in the affected twin. MR measures of medial temporal lobe atrophy have greater agreement with clinical data than do SPET measures of cerebral perfusion. Evaluation of atrophy may be useful in the early diagnosis of AD.