Alzheimer Disease: Boada M

Blesa R, Aguilar M, Casanova JP, Boada M, Martínez S, Alom J, de la Hoz CH, Sancho J, Fernández O, Gil-Neciga E, Massó JF. · Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Alzheimer Dis Assoc Disord. · Pubmed #17132969 No free full text.

Abstract: Alzheimer disease is the most common form of dementia in Western countries and the leading cause of disability in the over-65 population. Apolipoprotein E (APOE) is a multifunctional protein implied in lipid metabolism and neurobiology. Polymorphisms of the APOE gene have been associated with a variety of medical disorders, from arteriosclerosis to AD. A high frequency of the APOE epsilon4 allele has been found in patients with AD and they seem to have a higher risk of developing the disease. Various authors have suggested a possible relationship between the efficacy of cholinesterase inhibitors and the presence of the APOE epsilon4 allele. The purpose of the present study was to compare prospectively the efficacy of rivastigmine in patients with mild to moderately severe AD presenting different polymorphisms of the APOE gene on chromosome 19 and to determine if there was a difference in the response to rivastigmine treatment in AD patients with the APOE epsilon4 allele (heterozygous or homozygous) versus patients who had other forms of APOE, such as epsilon2 and epsilon3. This was an open-label, nonrandomized, multicenter study in patients over 50 years of age diagnosed with mild to moderately severe AD. The results of the analysis of this study indicate that the presence of at least one APOE epsilon4 allele does not determine a difference in the response to treatment with rivastigmine. The data indicate that knowledge of the patient's genotype is not necessary for treatment with rivastigmine. It would be interesting in the future to analyze the interaction between these 2 factors using other available anticholinesterase drugs.

Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C. · Federation of Neurology, CHU Pellegrin, Bordeaux, France. · Neurology. · Pubmed #12847155 No free full text.

Abstract: BACKGROUND: AD is characterized by cerebral deposition of beta-amyloid plaques with amyloid beta-peptide (Abeta) 42 as the major peptide constituent, along with neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Abeta42 removes these plaques and improves cognitive function. A Phase I study in AD patients demonstrated good safety and tolerability of multiple injections of aggregated Abeta42 (AN1792) with QS-21 as adjuvant. METHODS: Three hundred seventy-two patients with mild to moderate AD were randomized to receive IM injections of AN1792 or placebo (4:1) at baseline and at months 1, 3, 6, 9, and 12 in a multicenter Phase II safety, tolerability, and pilot efficacy study. Dosing was terminated after four early reports of meningoencephalitis, but follow-up continued. The study remains blinded, and further results will be reported after its termination. RESULTS: Symptoms and laboratory findings consistent with meningoencephalitis occurred in 18 of 298 (6%) patients treated with AN1792 compared with 0 of 74 on placebo (p = 0.020). Sixteen of the 18 had received two doses, one had received one dose, and one had received three doses of the study drug before symptoms occurred. The median latency from the first and last injections to symptoms was 75 and 40 days. No case occurred later than 6 months after the first immunization. Anti-Abeta42 antibody titers were not correlated with the occurrence or severity of symptoms or relapses. Twelve patients recovered to or close to baseline within weeks, whereas six remain with disabling cognitive or neurologic sequelae. All 18 patients remain alive to date (December 31, 2002), 6 months to >1 year after symptom onset. CONCLUSIONS: Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD.

Visser PJ, Verhey FR, Boada M, Bullock R, De Deyn PP, Frisoni GB, Frolich L, Hampel H, Jolles J, Jones R, Minthon L, Nobili F, Olde Rikkert M, Ousset PJ, Rigaud AS, Scheltens P, Soininen H, Spiru L, Touchon J, Tsolaki M, Vellas B, Wahlund LO, Wilcock G, Winblad B. · Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands. · Neuroepidemiology. · Pubmed #18515975 No free full text.

Abstract: BACKGROUND: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. METHODS: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2-3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. RESULTS: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.

Gómez-Isla T, Blesa R, Boada M, Clarimón J, Del Ser T, Domenech G, Ferro JM, Gómez-Ansón B, Manubens JM, Martínez-Lage JM, Muñoz D, Peña-Casanova J, Torres F, Anonymous00218. · Neurology Department, Hospital Santa Cruz y San Pablo and Centro de Investigación Biomédica en Red (CIBERNED), Lisboa, Spain. · Alzheimer Dis Assoc Disord. · Pubmed #18317243 No free full text.

Abstract: BACKGROUND: Amnestic mild cognitive impairment represents, in many cases, the earliest clinical phases of Alzheimer disease. Anti-inflammatory agents have epidemiologic support as drugs potentially beneficial in Alzheimer disease. In vivo studies have shown that Triflusal and its active metabolite 2-hydroxy-4-trifluoromethyl-benzoic acid have potent anti-inflammatory actions in the central nervous system. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of Triflusal in patients with amnestic mild cognitive impairment. Subjects were randomly assigned to receive 900 mg of Triflusal or placebo for 18 months. The primary outcome was a change in Cognitive subscale of the Alzheimer Disease Assessment Scale; conversion to dementia was a secondary outcome. RESULTS: A slow rate of recruitment forced a premature cessation of the study. Two hundred and fifty-seven subjects were enrolled and followed-up for an average of 13 months. The significance level was not reached for the primary outcome even though a trend in favor of Triflusal was observed. However, there was a significant difference in the probability of progression to dementia of Alzheimer's type with a lower risk in the Triflusal compared with the placebo group (hazard ratio, 2.10; 95% confidence interval, 1.10-4.01; P=0.024). CONCLUSIONS: In this study, Triflusal therapy was associated with a significant lower rate of conversion to dementia that is likely to be clinically relevant. Because the trial was prematurely halted, these results should be interpreted with caution and require further confirmation.

Unzeta M, Solé M, Boada M, Hernández M. · Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain. · J Neural Transm. · Pubmed #17393059 No free full text.

Abstract: One of the key pathological features of the progressive neurodegenerative disorder Alzheimer's disease (AD) is cerebral amyloid angiopathy (CAA). CAA is present in most cases of AD, and it is characterized by the deposition of beta-amyloid (Abeta) in brain vessels, inducing the degeneration of vascular smooth muscle cells and endothelial cells. Herein we report that semicarbazide-sensitive amine oxidase (SSAO) is overexpressed in cerebrovascular tissue of patients with AD-CAA, and that it colocalizes with beta-amyloid deposits. This over-expression correlates with high SSAO activity in plasma of severe AD patients. In addition, we have observed that the catalytic activity of SSAO is able to induce apoptosis in smooth muscle cells in vitro. Taken together, these results allow us to postulate that SSAO may contribute to the vascular damage associated to AD.

Pérez E, Barrachina M, Rodríguez A, Torrejón-Escribano B, Boada M, Hernández I, Sánchez M, Ferrer I. · Institut de Neuropatologia, Servei Anatomia Patològica, Hospital Universitari de Bellvitge, carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain. · Brain Res. · Pubmed #17123487 No free full text.

Abstract: Abnormalities in the cerebral microvasculature are common in Alzheimer disease (AD). Expression levels of the water channels aquaporin 1 and aquaporin 4 (AQP1, AQP4) were examined in AD cases by gel electrophoresis and Western blotting, and densitometric values normalized with beta-actin were compared with corresponding values in age-matched controls processed in parallel. In addition, samples of cases with Pick disease (PiD) were examined for comparative purposes. A significant increase in the expression levels of AQP1 was observed in AD stage II (following Braak and Braak classification). Individual variations were seen in advanced stages which resulted in non-significant differences between AD stages V-VI and age-matched controls. No differences in AQP1 levels were observed between familial AD cases (FAD, all of them at advanced stages) and corresponding age-matched controls. Immunohistochemistry showed increased AQP1 in astrocytes at early stages of AD. Double-labelling immunofluorescence and confocal microscopy disclosed AQP1 immunoreactivity at the cell surface of astrocytes which were recognized with anti-glial fibrillary acidic protein antibodies. No differences in the levels of AQP4 were observed in AD, FAD and PiD when compared with corresponding controls. These results indicate abnormal expression of AQP1 in astrocytes in AD, and they add support to the idea that abnormal regulation of mechanisms involved in the control of water fluxes occurs at early stages in AD.

Tárraga L, Boada M, Modinos G, Espinosa A, Diego S, Morera A, Guitart M, Balcells J, López OL, Becker JT. · Fundació ACE, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 35-37, 08014 Barcelona, Spain. · J Neurol Neurosurg Psychiatry. · Pubmed #16820420 No free full text.

Abstract: OBJECTIVE: To determine the usefulness of an interactive multimedia internet-based system (IMIS) for the cognitive stimulation of Alzheimer's disease. METHODS: This is a 24-week, single-blind, randomised pilot study conducted on 46 mildly impaired patients suspected of having Alzheimer's disease receiving stable treatment with cholinesterase inhibitors (ChEIs). The patients were divided into three groups: (1) those who received 3 weekly, 20-min sessions of IMIS in addition to 8 h/day of an integrated psychostimulation program (IPP); (2) those who received only IPP sessions; and (3) those who received only ChEI treatment. The primary outcome measure was the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Secondary outcome measures were: Mini-Mental State Examination (MMSE), Syndrom Kurztest, Boston Naming Test, Verbal Fluency, and the Rivermead Behavioral Memory Test story recall subtest. RESULTS: After 12 weeks, the patients treated with both IMIS and IPP had improved outcome scores on the ADAS-Cog and MMSE, which was maintained through 24 weeks of follow-up. The patients treated with IPP alone had better outcome than those treated with ChEIs alone, but the effects were attenuated after 24 weeks. All patients had improved scores in all of the IMIS individual tasks, attaining higher levels of difficulty in all cases. CONCLUSION: Although both the IPP and IMIS improved cognition in patients with Alzheimer's disease, the IMIS program provided an improvement above and beyond that seen with IPP alone, which lasted for 24 weeks.

Boada M, Tárraga L, Modinos G, Diego S, Reisberg B. · Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona. · Neurologia. · Pubmed #16525922 links to  free full text

Abstract: INTRODUCTION: The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a screening instrument for the evaluation of behavioral disturbances in Alzheimer's patients. Our aim was to validate the BEHAVE-AD test in Spanish, intended for use in routine clinical practice. METHOD: We assessed the validity of the BEHAVEAD in 79 nursing-home patients with diagnosis criteria of dementia, scoring 4 or higher on the Global Deterioration Scale (GDS) scale, by developing a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and BEHAVE-AD tests. Both instruments were rated by an expert clinician. In order to study the concurrent validity of some of the BEHAVE-AD subscales, we compared the Cohen-Mansfield Agitation Inventory (CMAI) and the Hamilton Depression Rating Scale (HDRS) tests. RESULTS: The Pearson correlation index between the BEHAVE-AD test and the NPI-Q, was significant but moderate (r=0.694). Pearson's correlation between BEHAVEAD's symptoms scale and NPI-Q's severity scale was r=0.698. When comparing BEHAVE-AD's global evaluation scale (caregiver's disturbance) and NPI-Q's distress scale, the correlation index was 0.535. CONCLUSIONS: The BEHAVE-AD Spanish version offers the possibility to use a screening tool for the detection of neuropsychiatric symptoms in dementia patients, also applicable to nursing home residents, administered by an expert clinician.

del Mar Hernandez M, Esteban M, Szabo P, Boada M, Unzeta M. · Departament de Bioquímica i Biología Molecular, Institut de Neurociencies, Facultat de Medicina, Universitat Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. · Neurosci Lett. · Pubmed #15894424 No free full text.

Abstract: Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines. The final products of its catalysis, ammonia, hydrogen peroxide (H2O2) and the corresponding aldehyde, may contribute to diseases involving vascular degeneration. SSAO is selectively expressed in blood vessels in the brain, but is also present in blood plasma. We have previously reported that membrane-bound SSAO is overexpressed in the cerebrovascular tissue of Alzheimer's disease (AD) patients. The aim of the present work is to study whether the circulating SSAO is also altered in this neurodegenerative disease. SSAO activity was determined in plasma of control cases (n = 23) and patients suffering sporadic Alzheimer dementia, distributed according to the Global Deterioration Scale (GDS): mild (n = 33), moderate (n = 14), moderate-severe (n = 15) and severe dementia (n = 19). Results show a clear increase of plasma SSAO activity (p < 0.001) in moderate-severe and severe AD patients, with patient age being an independent correlative factor. However, plasma SSAO activity was not altered in AD patients with mild or moderate dementia compared to controls. beta-Amyloid (Abeta) (40-42) immunoreactivity in plasma samples was also determined, and no correlation was observed between Abeta 40-42 levels and the severity of the dementia or the plasma SSAO activity. Our results suggest that an increase in circulating SSAO activity could contribute to oxidative stress and vascular damage in advanced Alzheimer's disease.

Armstrong J, Boada M, Rey MJ, Vidal N, Ferrer I. · Institut de Neuropatologia, Servei d'Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, 08907 Hospitalet de Llobregat, Spain. · Neurosci Lett. · Pubmed #15488330 No free full text.

Abstract: Mutations in APP are associated with familial early-onset Alzheimer disease (FAD). Examination of the genomic sequence in one patient with FAD revealed a change located in the axon 17 of the APP gene at position 275329G>A (GenBank accession number: D87675; GI: 2429080); cDNA sequence 2137G>A (GenBank accession number: X06989; GI: 28720). This corresponds to the mutation A713T in APP. AD stage VI of neurofibrillary degeneration and stage C of Abeta-amyloid burden was found at the post-mortem neuropathological examination. Previous studies have suggested that the mutation A713T in APP is a silent mutation or polymorphism. However, we have not found this change in APP in a control population analyzed by the amplification-refractory mutation system (ARMS). It is concluded that A713T in APP is implicated in the pathogenesis of AD. Since the immunohistochemical study indicates that A713T mutation is not likely to relate with Abeta-amyloid processing, the causative role of this rare mutation remains to be warranted.

Planas M, Conde M, Audivert S, Pérez-Portabella C, Burgos R, Chacón P, Rossello J, Boada M, Tàrraga LL. · Nutritional Support Unit, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain. · Clin Nutr. · Pubmed #15030967 No free full text.

Abstract: OBJECTIVE: To evaluate if nutritional supplementation with or without micronutrient enhancement prevent weight loss and the progression of the disease in mild Alzheimer's Disease (AD) patients. DESIGN: Mild AD patients were recruited from an Alzheimer Day Centre. Subjects received oral liquid supplements with (Study-group: S) or without (Control-group: C) micronutrient enhancement. Intake assessment, nutritional status, biochemical parameters, cognitive function, and eating behaviour disorders were determined at baseline and at 6 months of treatment. RESULTS: At baseline both groups were not different in any variable measured. They were norm nourished, with normal biochemical parameters. Blandford scale demonstrated a mild alteration of feeding behaviour, the cognitive scale classified the patients as impaired and there was presence of memory complaints. After 6 months of nutritional supplements, a similar increase in energy consumption was observed in both groups of patients (P<0.05). In the within-group analysis, we found a trend (P=0.05) to increase body mass index; a significant increase in triceps skin fold thickness, mid-upper-arm circumference and serum magnesium, zinc and selenium, and a significant reduction in serum vitamin E (P<0.001, each). Serum cholesterol decreased substantially only in the S-group (P=0.025). No significant differences at baseline, within-group, neither between-group analysis in feeding behaviour nor in cognitive function were observed. CONCLUSIONS: According to our results no benefits in the progression of the disease was observed with micronutrient enhancement supplements. Effectiveness of nutritional supplements in preventing weight loss in mild AD patients showed a similar behaviour as observed in other populations. Due to the beneficial evolution of serum cholesterol in the S-group, this intervention deserves further investigation.

Clarimón J, Bertranpetit J, Boada M, Tàrraga L, Comas D. · Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain. · J Geriatr Psychiatry Neurol. · Pubmed #12967056 No free full text.

Abstract: Neuropsychiatric manifestations are common in Alzheimer's disease (AD) and their phenotypic expression might be related to physiopathological and genetic causes. Multiple studies have implicated oxidative stress to the pathogenesis and possible etiology of AD. One of the mechanisms to protect cells from oxidative stress is the expression of heat-shock proteins (HSP). HSPA1B (alternatively known as HSP70-2) has been related to AD pathophysiology. In the present analysis, 77 AD patients were classified according to their cognitive status with the Neuropsychiatric Inventory and were genotyped for an insertion/deletion (A1/A2) polymorphism. The A2 allele conferred a significant increase of psychiatric morbidity in an allele-dose manner (P < .05). This pattern can be attributed to all AD stages and the severity of the behavioral disturbances was higher for those patients carrying one or two A2 alleles. These results indicate a possible association between the A2 allele and an overexpression of noncognitive symptoms in AD.

Clarimón J, Bertranpetit J, Calafell F, Boada M, Tàrraga L, Comas D. · Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Doctor Aiguader 80, 08003 Barcelona, Spain. · J Neurol. · Pubmed #12928915 No free full text.

Abstract: BACKGROUND: Amyloid beta-peptide (Abeta) biosynthesis, aggregation and degradation constitute three important steps to consider in the study of pathological mechanisms involved in Alzheimer's disease (AD). Several proteins have been suggested as involved in each of these processes: proteolytic cleavage of the amyloid precursor protein by the beta-site APP cleaving enzyme (BACE), increased amyloid fibril formation by the activity of the acetylcholinesterase (ACHE gene), and degradation of Abeta aggregates by the plasmin system have been exhaustively documented. METHODS: A case-control design was used to evaluate the possible association between candidate genes involved in these three processes and AD. We analysed three polymorphisms located at the BACE1 gene, one polymorphism at the ACHE gene, and two variants located at the tissue plasminogen activator and plasminogen activator inhibitor-1 (genes TPA and PAI- 1, respectively), both part of the plasmin system. RESULTS: We found an association between BACE1 exon 5 GG genotype and AD (age-and gender-adjusted odds ratio = 2.14, P =0.014). Although a similar association was reported previously by Nowotny and collaborators only in subjects carrying the epsilon4-allele of the apolipoprotein E gene (APOE), we did not detect this effect. However,when we combined our results with those previously reported, a clear increase of the risk to develop AD appeared in subjects carrying both the BACE1 exon 5 GG genotype and the APOE epsilon4-allele (crude OR = 2.2, P = 0.004). CONCLUSION: These data suggest a possible genetic relation between BACE1 and AD.

Clarimón J, Bertranpetit J, Calafell F, Boada M, Tàrraga L, Comas D. · Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain. · Psychiatr Genet. · Pubmed #12782964 No free full text.

Abstract: BACKGROUND: Besides the repeated association between the epsilon 4 allele of the apolipoprotein E and Alzheimer's disease, several candidate genes have been analysed with inconsistent results. Most of these studies have examined only one or two polymorphisms in a defined population, which provides a lack of a general view of the Alzheimer's disease genetic component. OBJECTIVE: To overcome this limitation, nine polymorphisms in seven different candidate genes (A2M, ACT, APOE, APP, BH, HSP70-2, and IL1-A) were genotyped. METHODS: The sample comprised 112 Alzheimer's disease patients and 89 controls from Spain. Since haplotype reconstruction may add power to association studies, we also tested for linkage disequilibrium within the A2M and APOE genes. RESULTS: Except for the APOE gene, allele and genotype frequencies were not different between cases and controls, even when stratifying for the APOE genotype. CONCLUSION: The present results suggest that future association studies should be performed using a battery of polymorphisms in different and new candidate genes, taking into account the linkage disequilibrium in the region.

Clarimón J, Muñoz FJ, Boada M, Tàrraga L, Sunyer J, Bertranpetit J, Comas D. · Unitat de Biologia Evolutiva, Universitat Pompeu Fabra, Barcelona, Spain. · J Neural Transm. · Pubmed #12768360 No free full text.

Abstract: Neprilysin has recently been reported to be the major physiological Abeta-degradating enzyme. In this study we describe a new biallelic polymorphism in the 3'UTR of the neprilysin gene in a representative population sample. The (*)159C/C genotype was found to be associated with an increased risk for Alzheimer's disease in an age-dependent manner. Adjusting for sex and APOE status, an odds ratio of 2.74 (p < 0.05) was observed among patients under 75 years old.

Boada M, Cejudo JC, Tàrraga L, López OL, Kaufer D. · Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain. · Neurologia. · Pubmed #12084358 links to  free full text

Abstract: BACKGROUND: The Neuropsychiatric Inventory (NPI) is a validated clinical instrument for the evaluation of psychopathology in dementia. OBJECTIVE: To validate a brief questionnaire form of the NPI (NPI-Q) in Spanish from NPI-Q original version, intended for use in routine clinical practice. PATIENTS AND METHOD: We have developed a crossed validated form between NPI and NPI-Q in 120 Alzheimer's disease patients. RESULTS: Test-retest reliability of the NPI-Q, using Pearson correlation index was r = 0.89 for total symptom scale and r = 0.90 for distress scale. The prevalence of analogous symptom ratings differed by less than 6.7%. Convergent validity between NPI-Q and NPI, using Pearson correlation index was r = 0.879 for total symptom and r = 0.92 for distress scale. CONCLUSIONS: The NPI-Q Spanish version offers the possibility to use a reliable and brief instrument that can be used as a screening in the evaluation of neuropsychiatric symptoms in dementia and associated caregiver distress. It may be suitable for use in general clinical practice and it could be used as a brief neuropsychiatric interview.

Boada M, Peña-Casanova J, Bermejo F, Guillén F, Hart WM, Espinosa C, Rovira J. · Servico de Neurología, Hospital de la Vall d'Hebron, Barcelona. · Med Clin (Barc). · Pubmed #10650570 No free full text.

Abstract: BACKGROUND: The annual consumption and costs of the health care resources used by ambulatory Alzheimer's disease patients were estimated. Patients were classified according to the degree of severity of the disease using Folstein's Mini Mental State Examination scale. The sociodemographic characteristics of both patients and their careers were described. PATIENTS AND METHODS: Patients with an established diagnosis of Alzheimer's disease according to NINCDS/ADRDA criteria were included in the study. Information on the use of health and non-health care resources consumed during the last 12 months was recorded. The following scales were administered: MMSE, Global Deterioration Scale, Rapid Disability Rating Scale and Hachinski's scale modified by Rosen. Finally, the time dedicated by careers to look after the Alzheimer's disease patients was recorded. RESULTS: A total of 337 patients were considered to be valid for the analysis with an average of 72 (8.4) years and with an average duration of the disease of 48.3 (35.7) months. The average annual cost per patient was 3,194,664 ptas. The average cost per patient in the group with MMSE > 18 was 2,119,889 ptas; 2,723,159 ptas. in those with MMSE 12-18 and 3,676,707 ptas. in the MMSE < 12 group. CONCLUSIONS: In patients with Alzheimer's disease an increase in cost directly related to functional cognition state was observed. The most important cost component was that imputed to value time dedicated by principal career.