Whipple's Disease With Neurological Manifestations: Case Report

Whipple's disease (WD) is an uncommon multisystem condition caused by the bacillus Tropheryma whipplei. Central nervous system involvement is a classical feature of the disease observed in 20 to 40% of the patients. We report the case of a 62 yeards old man with WD that developed neurological manifestations during its course, and discuss the most usual signs and symptoms focusing on recent diagnostic criteria and novel treatment regimens.622 A342346Whipple, G.H., A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues (1907) Johns Hopkins Hosp Bull, 18, pp. 382-391Marth, T., Raoult, D., Whipple's disease (2003) Lancet, 36, pp. 239-246Gerard, A., Sarrot-Reynauld, F., Liozon, E., Neurologic presentation of Whipple disease: Report of 12 cases and review of the literature (2002) Medicine (Baltimore), 81, pp. 443-457Brown, A.P., Lane, J.C., Murayama, S., Vollmer, D.G., Whipple's disease presenting with isolated neurological symptoms: Case report (1990) J Neurosurg, 73, pp. 623-627Bostwick, D.G., Bensch, K.G., Burke, J.S., Whipple's disease presenting as aortic insufficiency (1981) N Engl J Med, 305, pp. 995-998Raoult, D., A febrile, blood culture-negative endocarditis (1999) Ann Intern Med, 131, pp. 144-146Chan, R.Y., Yannuzzi, L.A., Foster, C.S., Ocular Whipple's disease: Earlier definitive diagnosis (2001) Ophthalmology, 108, pp. 2225-2231Louis, E.D., Lynch, T., Kaufmann, P., Fahn, S., Odel, J., Diagnostic guidelines in central nervous system Whipple's disease (1996) Ann Neurol, 40, pp. 561-568Sieracki, J.C., Whipple's disease: Observations on systemic involvement (1958) Amer Med Asso Arch Pathol, 66, pp. 464-467Anderson, M., Neurology of Whipple's disease (2000) J Neurol Neurosurg Psychiatry, 68, pp. 2-5De Coene, B., Gilliard, C., Indekeu, P., Whipple's disease confined to the central nervous system (1996) Neuroradiology, 38, pp. 325-327Verhagen, W.I.M., Huygen, P.L.M., Dalman, J.E., Schuurmans, M.M.J., Whipple's disease and the central nervous system: A case report and a review of the literature (1996) Clin Neurol Neurosurg, 98, pp. 299-304Feldman, M., Hendler, R.S., Morrison, E.B., Acute meningoencephalitis after withdrawal of antibiotics in Whipple's disease (1980) Ann Intern Med, 93, pp. 709-711Schwartz, M.A., Selhorst, J.B., Ochs, A.L., Oculomasticatory myorhythmia: A unique movement disorder occurring in Whipple's disease (1986) Ann Neurol, 20, pp. 677-683Manzel, K., Tranel, D., Cooper, G., Cognitive and behavioral abnormalities in a case of central nervous system Whipple disease (2000) Arch Neurol, 57, pp. 399-403Halperin, J.J., Landis, D.M., Kleinman, G.M., Whipple's disease of the nervous system (1982) Neurology, 32, pp. 612-617Feurle, G.E., Volk, B., Waldherr, R., Cerebral Whipple's disease with negative jejunal histology (1979) N Engl J Med, 300, pp. 907-908Madoule, P., Ciaudio-Lacroix, C., Halimi, P., Osteoarticular lesions in Whipple's disease, a propos of a destructive form and review of the literature (1985) J Radiol, 66, pp. 345-350Brändle, M., Ammann, P., Spinas, G.A., Relapsing Whipple's disease presenting with hypopituitarism (1999) Clin Endocrinol, 50, pp. 399-403Topper, R., Gartung, C., Block, F., Neurologic complications in inflammatory bowel diseases (2002) Nervenarzt, 73, pp. 489-499Clarke, C.E., Falope, Z.F., Abdelhadi, H.A., Cervical myelopathy caused by Whipple's disease (1998) Neurology, 50, pp. 1505-1506Ramzan, N.N., Loftus, E., Burgart, L.J., Diagnosis and monitoring of Whipple disease by polymerase chain reaction (1997) Ann Intern Med, 126, pp. 520-527Von Herbay, A., Ditton, H.J., Scuhmacher, F., Whipple's disease: Staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid (1997) Gastroenterology, 113, pp. 434-441Kremer, S., Besson, G., Bonaz, B., Pasquier, B., Le Bas, J.F., Grand, S., Diffuse lesions in the CNS revealed by MR imaging in a case of Whipple disease (2001) Am J Neuroradiol, 22, pp. 493-495Romanul, F.C., Radvany, J., Rosales, R.K., Whipple's disease confined to the brain: A case studied clinically and pathologically (1977) J Neurol Neurosurg Psychiatry, 40, pp. 901-909Thompson, D.G., Leidingham, J.M., Howard, A.J., Brown, C.L., Meningitis in Whipple's disease (1978) BMJ, 2, pp. 14-15Feurle, G.E., Marth, T., An evaluation of antimicrobial treatment for Whipple's disease: Tetracycline versus trimethoprim-sulfamethoxazole (1994) Dig Dis Sci, 39, pp. 1642-1648Misbah, S.A., Mapstone, N.P., Whipple's disease revisited (2000) J Clin Pathol, 53, pp. 750-755Schnider, P.J., Reisinger, E.C., Berger, T., Krejs, G.J., Auff, E., Treatment guidelines in central nervous system Whipple's disease (1997) Ann Neurol, 41, pp. 561-56

Dementias [demências]

Dementias are clinical conditions increasingly prevalent in our society and doctors from different specialties should be able to diagnose and treat these diseases. In this article, we discuss mainly the clinical and therapeutic aspects of the most common forms of neurodegenerative dementias, with emphasis on Alzheimer's disease. © Copyright Moreira Jr. Editora.686183193Dugué, M., Neugroschl, J., Sewell, M., Marin, D., Review of dementia (2003) Mt Sinai J Med, 70 (1), pp. 45-53. , JanPfeffer, R.I., Kurosaki, T.T., Harrah Jr., C.H., Measurement of functional activities in older adults in the community (1982) Journals of Gerontology, 37 (3), pp. 323-329(1994) Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, , American Psychiatric Association., American Psychiatric Association. Task Force on DSM-IV. 4th ed. Washington, DC: American Psychiatric AssociationPalmer, K., Fratiglioni, L., Winblad, B., What is mild cognitive impairment? Variations in definitions and evolution of nondemented persons with cognitive impairment (2003) Acta Neurol Scand Suppl, 179, pp. 14-20Kelley, B.J., Petersen, R.C., Alzheimer's Disease and Mild Cognitive Impairment (2007) Neurologic Clinics, 25 (3), pp. 577-609. , DOI 10.1016/j.ncl.2007.03.008, PII S0733861907000540, DementiaDevanand, D.P., Pradhaban, G., Liu, X., Khandji, A., De Santi, S., Segal, S., Rusinek, H., De Leon, M.J., Hippocampal and entorhinal atrophy in mild cognitive impairment: Prediction of Alzheimer disease (2007) Neurology, 68 (11), pp. 828-836. , DOI 10.1212/01.wnl.0000256697.20968.d7, PII 0000611420070313000009Jack Jr., C.R., Petersen, R.C., Xu, Y.C., O'Brien, P.C., Smith, G.E., Ivnik, R.J., Boeve, B.F., Kokmen, E., Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment (1999) Neurology, 52 (7), pp. 1397-1403Cummings, J.L., Alzheimer's Disease (2003) The Neuropsychiatry of Alzheimer's Disease and Related Dementias, pp. 57-116. , Cummings JL. London: Martin Dunitz EdCummings, J.L., Cole, G., Alzheimer Disease (2002) JAMA, 18, pp. 2335-2338Herrera Jr., E., Caramelli, P., Silveira, A.S., Nitrini, R., Epidemiologic Survey of Dementia in a Community-Dwelling Brazilian Population (2002) Alzheimer Disease and Associated Disorders, 16 (2), pp. 103-108Wilmo, A., Jonsson, L., Winblad, B., An estimate of the worldwide prevalence and direct costs of dementia in 2003 (2006) Dement Geriatr Cogn Disord, 21 (3), pp. 175-181Eckman, C.B., Eckman, E.A., An update on the amyloid hypothesis (2007) Neurol Clin, 25, pp. 669-682Morris, J.C., Dementia update 2005 (2005) Alzheimer Dis Assoc Disord, 19, pp. 100-117Nitrini, R., Caramelli, P., Bottino, C.M., Damasceno, B.P., Brucki, S.M., Anghinah, R., Diagnosis of Alzheimer's disease in Brazil: Diagnostic criteria and auxiliary tests. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2005) Arq Neuropsiquiatr, 63 (3 A), pp. 713-719. , SepScahill, R.I., Frost, C., Jenkins, R., Whitwell, J.L., Rossor, M.N., Fox, N.C., A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging (2003) Archives of Neurology, 60 (7), pp. 989-994. , DOI 10.1001/archneur.60.7.989Chantal, S., Labelle, M., Bouchard, R.W., Braun, C.M.J., Boulanger, Y., Correlation of regional proton magnetic resonance spectroscopic metabolic changes with cognitive deficits in mild Alzheimer disease (2002) Archives of Neurology, 59 (6), pp. 955-962Hansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., Minthon, L., Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: A follow-up study (2006) Lancet Neurology, 5 (3), pp. 228-234. , DOI 10.1016/S1474-4422(06)70355-6, PII S1474442206703556Engelhardt, E., Brucki, S.M., Cavalcanti, J.L., Forlenza, O.V., Laks, J., Vale, F.A., Treatment of Alzheimer's disease: Recommendations and suggestions of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2005) Arq Neuropsiquiatr, 63 (4), pp. 1104-1112. , DecMayeux, R., Clinical practice. Early Alzheimer's disease (2010) N Engl J Med, 362 (23), pp. 2194-2201. , Jun 10Reisberg, B., Doody, R., Stöffler, A., A randomized, placebo-controlled study of memantine, an uncompetitive NMDAantagonist, in patients with moderate to severe Alzheimer's disease (2003) N Engl J Med, 348, pp. 1333-1341Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P., Kivipelto, M., Alzheimer's disease: Clinical trials and drug development (2010) Lancet Neurol, 9 (7), pp. 702-716. , JulCaixeta, L., Chaves, M., Sintomas psicologicos e comportamentais na demência e seu tratamento farmacológico (2006) Demência: Abordagem Multidisciplinar, pp. 519-530. , Caixeta L. São Paulo: Ed. AtheneuRoman, G.C., Tatemichi, T.K., Erkinjuntti, T., Cummings, J.L., Masdeu, J.C., Garcia, J.H., Amaducci, L., Kokmen, E., Vascular dementia: Diagnostic criteria for research studies: Report of the NINDS-AIREN International Workshop (1993) Neurology, 43 (2), pp. 250-260Assal, F., Bogousslavsky, J., Clinical and therapeutic aspects of vascular dementia (2008) Handbook of Clinical Neurology, 89, pp. 659-670. , Duyckaerts C, Litvan I. Dementias. Amsterdan: Eiservier EdEngelhardt, E., Caramelli, P., Bottino, C.M., Vale, F.A., Barbosa, M.T., Brucki, S.M., Doença de Alzheimer com doença cerebrovascular e demência mista: Atualização diagnóstica e terapêutica (2010) CoBEAI, 2 (1), pp. 49-72Serby, M., Samuels, S.C., Diagnostic criteria for dementia with lewy bodies reconsidered (2001) American Journal of Geriatric Psychiatry, 9 (3), pp. 212-216. , DOI 10.1176/appi.ajgp.9.3.212McKeith, I., Clinical aspects of Dementia with Lewy bodies (2008) Handbook of Clinical Neurology, 89, pp. 307-311. , Duyckaerts C, Litvan I. Dementias. Amsterdan: Eiservier EdRabinovic, G.D., Rascovsky, K., Miller, B.L., Frontotemporal lobar degeneration: Clinical and pathological overview (2008) Handbook of Clinical Neurology, 89, pp. 343-364. , Duyckaerts C, Litvan I. Dementias. Amsterdan: Eiservier EdGrossman, M., Primary progressive aphasia: Clinicopathological correlations (2010) Nat Rev Neurol, 6 (2), pp. 88-97. , FebSilverberg, G.D., Normal pressure hydrocephalus (NPH): Ischaemia, CSF stagnation or both (2004) Brain, 127 (5), pp. 947-948. , DOI 10.1093/brain/awh178Miyati, T., Mase, M., Kasai, H., Hara, M., Yamada, K., Shibamoto, Y., Soellinger, M., Luechinger, R., Noninvasive MRI assessment of intracranial compliance in idiopathic normal pressure hydrocephalus (2007) Journal of Magnetic Resonance Imaging, 26 (2), pp. 274-278. , DOI 10.1002/jmri.20999Albeck, M.J., Skak, C., Nielsen, P.R., Olsen, K.S., Borgesen, S.E., Gjerris, F., Age dependency of resistance to cerebrospinal fluid outflow (1998) Journal of Neurosurgery, 89 (2), pp. 275-278Damasceno, B.P., Carelli, E.F., Honorato, D.C., Facure, J.J., The predictive value of cerebrospinal fluid tap-test in normal pressure hydrocephalus (1997) Arquivos de Neuro-Psiquiatria, 55 (2), pp. 179-185Caixeta, L., Demência na hidrocefalia de pressão normal (2006) Demência: Abordagem Multidisciplinar, pp. 463-470. , Caixeta L. São Paulo: Ed. Atheneu;Brucki, S.M., Nitrini, R., Caramelli, P., Bertolucci, P.H., Okamoto, I.H., Suggestions for utilization of the mini-mental state examination in Brazil (2003) Arq Neuropsiquiatr, 61 (3 B), pp. 777-781. , SepBrucki, S.M.D., Rocha, M.S.G., Category fluency test: Effects of age, gender and education on total scores, clustering and switching in Brazilian Portuguese-speaking subjects (2004) Brazilian Journal of Medical and Biological Research, 37 (12), pp. 1771-1777Aprahamian, I., Martinelli, J.E., Neri, A.L., Yassuda, M.S., The Clock Drawing Test: Review of its accuracy in screening for dementia (2009) Dem Neuropsy, 3 (2), pp. 74-8

Neural Correlates Of Lexical-semantic Memory: A Voxel-based Morphometry Study In Mild Ad, Amci And Normal Aging [correlatos Neurais Da Memória Lexical-semântica: Um Estudo De Morfometria Baseada Em Voxel Na Doença De Alzheimer, Comprometimento Cognitivo Leve Amnéstico E Envelhecimento Normal]

Neuroanatomical correlations of naming and lexical-semantic memory are not yet fully understood. The most influential approaches share the view that semantic representations reflect the manner in which information has been acquired through perception and action, and that each brain area processes different modalities of semantic representations. Despite these anatomical differences in semantic processing, generalization across different features that have similar semantic significance is one of the main characteristics of human cognition. Methods: We evaluated the brain regions related to naming, and to the semantic generalization, of visually presented drawings of objects from the Boston Naming Test (BNT), which comprises different categories, such as animals, vegetables, tools, food, and furniture. In order to create a model of lesion method, a sample of 48 subjects presenting with a continuous decline both in cognitive functions, including naming skills, and in grey matter density (GMD) was compared to normal young adults with normal aging, amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). Semantic errors on the BNT, as well as naming performance, were correlated with whole brain GMD as measured by voxel-based morphometry (VBM). Results: The areas most strongly related to naming and to semantic errors were the medial temporal structures, thalami, superior and inferior temporal gyri, especially their anterior parts, as well as prefrontal cortices (inferior and superior frontal gyri). Conclusion: The possible role of each of these areas in the lexical-semantic networks was discussed, along with their contribution to the models of semantic memory organization.526977Luria, A.R., (1986) The Word and Its Semantic Structure. 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The representation of semantic knowledge in the human brain (2007) Nat Rev Neurosci, 8, pp. 976-987Martin, A., Chao, L.L., Semantic memory and the brain: Structure and processes (2001) Curr Opin Neurobiol, 11, pp. 194-201Albert, M.S., Heller, H.S., Milberg, W., Changes in naming ability with age (1988) Psychol Aging, 3, pp. 173-178Labarge, E., Edwards, D., Knesevich, J.W., Performance of normal elderly on the Boston Naming Test (1986) Brain Lang, 27, pp. 380-384Zec, R.F., Markwell, S.J., Burkett, N.R., Larsen, D.L., A longitudinal study of confrontation naming in the "normal" elderly (2005) J Int Neuropsychol Soc, 11, pp. 716-726Adlam, A.L., Bozeat, S., Arnold, R., Watson, P., Hodges, J.R., Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease (2006) Cortex, 42, pp. 675-684Dudas, R.B., Clague, F., Thompson, S.A., Graham, K.S., Hodges, J.R., Episodic and semantic memory in mild cognitive impairment (2005) Neuropsychologia, 43, pp. 1266-1276Winblad, B., Palmer, K., Kivipelto, M., Mild cognitive impairment--beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment (2004) J Int Med, 256, pp. 240-246Kaplan, E.F., Goodglass, H., Weintraub, S., (1983) The Boston Naming Test, , 2nd edition. 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"Mini-mental state": A practical method for grading the cognitive state of patients for the clinician (1975) J Psychiatr Res, 12, pp. 189-198Brucki, S.M., Nitrini, R., Caramelli, P., Bertolucci, P.H., Okamoto, I.H., Suggestions for utilization of the mini-mental state examination in Brazil (2003) Arq Neuropsiquiatr, 61, pp. 777-781Rey, A., (1964) Clinical Examination In Psychology, , Paris: Press Universitaire de FranceRoth, M., Huppert, F.A., Tym, E., Mountjoy, C.Q., (1988) CAMDEX: The Cambridge Examination For Mental Disorders of the Elderly, , Cambridge: Cambridge University PressChristensen, A.-L., (1979) Luria's Neuropsychological Investigation, p. 203. , Copenhagen: MunksgaardWechsler, D., (1987) Manual For the Wechsler Memory Scale-Revised (WMS-R), , San Antonio: The Psychological CorporationAlexopoulos, G.S., Abrams, R.C., Young, R.C., Shamoian, C.A., Cornell Scale for Depression in Dementia (1988) Biological Psychiatry, 23, pp. 271-284Carthery-Goulart, M.T., Areza-Fegyveres, R., Schultz, R.R., Brazilian version of the Cornell depression scale in dementia (2007) Arq Neuropsiquiatr, 65, pp. 912-915Ashburner, J., Friston, K.J., Unified segmentation (2005) NeuroImage, 26, pp. 839-851Bergougnian, L., Chupin, M., Czechowska, Y., Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression? (2009) Neuroimage, 45, pp. 29-37Rorden, C., Fridriksson, J., Karnath, H.O., An evaluation of traditional and novel tools for lesion behavior mapping (2009) Neuroimage, 44, pp. 1355-1362Balthazar, M.L., Cendes, F., Damasceno, B.P., Semantic error patterns on the Boston Naming Test in normal aging, amnestic mild cognitive impairment and mild Alzheimer's disease: Is there semantic disruption? 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Whole Cortical And Default Mode Network Mean Functional Connectivity As Potential Biomarkers For Mild Alzheimer's Disease

The search for an Alzheimer's disease (AD) biomarker is one of the most relevant contemporary research topics due to the high prevalence and social costs of the disease. Functional connectivity (FC) of the default mode network (DMN) is a plausible candidate for such a biomarker. We evaluated 22 patients with mild AD and 26 age- and gender-matched healthy controls. All subjects underwent resting functional magnetic resonance imaging (fMRI) in a 3.0. T scanner. To identify the DMN, seed-based FC of the posterior cingulate was calculated. We also measured the sensitivity/specificity of the method, and verified a correlation with cognitive performance. We found a significant difference between patients with mild AD and controls in average z-scores: DMN, whole cortical positive (WCP) and absolute values. DMN individual values showed a sensitivity of 77.3% and specificity of 70%. DMN and WCP values were correlated to global cognition and episodic memory performance. We showed that individual measures of DMN connectivity could be considered a promising method to differentiate AD, even at an early phase, from normal aging. Further studies with larger numbers of participants, as well as validation of normal values, are needed for more definitive conclusions. © 2013 Elsevier Ireland Ltd.22113742Adriaanse, S.M., Sanz-Arigita, E.J., Binnewijzend, M.A., Ossenkoppele, R., Tolboom, N., van Assema, D.M., Wink, A.M., van Berckel, B.N., Amyloid and its association with default network integrity in Alzheimer's disease (2012) Human Brain Mapping, electronic publication 14 December;, , (Online)Balthazar, M.L., Pereira, F.R., Lopes, T.M., da Silva, E.L., Coan, A.C., Campos, B.M., Duncan, N.W., Cendes, F., Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network (2013) Human Brain Mapping, electronic publication 18 February;, , (Online)Binnewijzend, M.A., Schoonheim, M.M., Sanz-Arigita, E., Wink, A.M., van der Flier, W.M., Tolboom, N., Adriaanse, S.M., Barkhof, F., Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment (2012) Neurobiology of Aging, 33, pp. 2018-2028Boyacioglu, R., Barth, M., Generalized iNverse imaging (GIN): ultrafast fMRI with physiological noise correction (2012) Magnetic Resonance in Medicine, electronic publication 24 October;, , (Online)Brucki, S.M., Nitrini, R., Caramelli, P., Bertolucci, P.H., Okamoto, I.H., Suggestions for utilization of the Mini-Mental State Examination in Brazil (2003) Arquivos de Neuro-psiquiatria, 61, pp. 777-781Buckner, R.L., Andrews-Hanna, J.R., Schacter, D.L., The brain's default network: anatomy, function, and relevance to disease (2008) Annals of the New York Academy of Sciences, 1124, pp. 1-38Celone, K.A., Calhoun, V.D., Dickerson, B.C., Atri, A., Chua, E.F., Miller, S.L., DePeau, K., Sperling, R., Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis (2006) Journal of Neuroscience, 26, pp. 10222-10231Christensen, A.-L., (1975), Luria's Neuropsychological Investigation, Manual and Test Material. Ed. Munksgaard, CopenhagenDaselaar, S.M., Prince, S.E., Dennis, N.A., Hayes, S.M., Kim, H., Cabeza, R., Posterior midline and ventral parietal activity is associated with retrieval success and encoding failure (2009) Frontiers in Human Neuroscience, 3, pp. 1-10De Martino, F., Esposito, F., van de Moortele, P.F., Harel, N., Formisano, E., Goebel, R., Ugurbil, K., Yacoub, E., Whole brain high-resolution functional imaging at ultra high magnetic fields: an application to the analysis of resting state networks (2011) NeuroImage, 57, pp. 1031-1044Drzezga, A., Becker, J.A., Van Dijk, K.R., Sreenivasan, A., Talukdar, T., Sullivan, C., Schultz, A.P., Sperling, R.A., Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden (2011) Brain, 134, pp. 1635-1646Folstein, M.F., Folstein, S.E., McHugh, P.R., "Mini-mental state". 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Structural Connectivity Of The Default Mode Network And Cognition In Alzheimer's Disease

Disconnectivity between the Default Mode Network (DMN) nodes can cause clinical symptoms and cognitive deficits in Alzheimer's disease (AD). We aimed to examine the structural connectivity between DMN nodes, to verify the extent in which white matter disconnection affects cognitive performance. MRI data of 76 subjects (25 mild AD, 21 amnestic Mild Cognitive Impairment subjects and 30 controls) were acquired on a 3.0. T scanner. ExploreDTI software (fractional Anisotropy threshold=0.25 and the angular threshold=60°) calculated axial, radial, and mean diffusivities, fractional anisotropy and streamline count. AD patients showed lower fractional anisotropy (P=0.01) and streamline count (P=0.029), and higher radial diffusivity (P=0.014) than controls in the cingulum. After correction for white matter atrophy, only fractional anisotropy and radial diffusivity remained significantly lower in AD compared to controls (P=0.003 and P=0.05). In the parahippocampal bundle, AD patients had lower mean and radial diffusivities (P=0.048 and P=0.013) compared to controls, from which only radial diffusivity survived for white matter adjustment (P=0.05). Regression models revealed that cognitive performance is also accounted for by white matter microstructural values. 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Treatment Of Alzheimer's Disease [tratamento Da Doença De Alzheimer]

[No abstract available]5SUPPL. 13448Engelhardt, E., Brucki, S.M., Cavalcanti, J.L., Forlenza, O.V., Laks, J., Vale, F.A., Treatment of Alzheimer's disease: Recommendations and suggestions of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2005) Arq Neuropsiquiatr, 63, pp. 1104-1112. , Departamento de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de NeurologiaGronseth, G., French, J., Practice parameters and technology assessments: What they are, what they are not, and why you should care (2008) Neurology, 71, pp. 1639-643French, J., Gronseth, G., Lost in a jungle of evidence: We need a compass (2008) Neurology, 71, pp. 1634-1638McKhann, G.M., Knopman, D.S., Chertkow, H., The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup (2011) Alzheimers Dement, 7, pp. 263-269McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., Stadlan, E.M., Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease (1984) Neurology, 34, pp. 939-944Albert, M.S., Dekosky, S.T., Dickson, D., Dubois, B., Feldman, H.H., Fox, N.C., (2011) The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging and Alzheimer's Association workgroup, , Alzheimers Dement Apr 20Sperling, R.A., Aisen, P.S., Beckett, L.A., Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup (2011) Alzheimers Dement, 7, pp. 280-292Nordberg, A., Nicotinic receptor abnormalities of Alzheimer's disease: Therapeutic implications (2001) Biol Psychiatry, 49, pp. 200-210Peters, B.H., Levin, H.S., Effects of physostigmine and lecitin on memory in Alzheimer's disease (1979) Ann Neurol, 6, pp. 219-221Summers, W.K., Majovski, L.V., Marsh, G.M., Tachiki, K., Kling, A., Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type (1986) N Engl J Med, 315, pp. 1241-1245Corey-Bloom, J., Anand, R., Veach, J., A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetyl-chonesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease (1998) Int. J Geriatr Psychopharmacol, 1, pp. 55-65Rogers, S.L., Farlow, M.R., Doody, R.S., Mohs, R., Friedhoff, L.T., A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group (1998) Neurology, 50, pp. 136-145Raskind, M.A., Peskind, E.R., Wessel, T., Yuan, W., Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. 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[Epub ahead of print]Winblad, B., Black, S.E., Homma, A., Donepezil treatment in severe Alzheimer's disease: A pooled analysis of three clinical trials (2009) Curr Med Res Opin, 25, pp. 2577-2587Jarvis, B., Figgitt, D.P., Memantine (2003) Drugs Aging, 20 (6), pp. 465-76. , discussion 477-8Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S., Möbius, H.J., Memantine in moderate-to-severe Alzheimer's disease (2003) N Engl J Med, 348, pp. 1333-1341. , Memantine Study GroupTariot, P.N., Farlow, M.R., Grossberg, G.T., Graham, S.M., McDonald, S., Gergel, I., Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial (2004) JAMA, 291, pp. 317-324. , Memantine Study GroupWinblad, B., Jones, R.W., Wirth, Y., Stoffler, A., Mobius, H.J., Memantine in moderate to severe Alzheimer's disease: A meta-analysis of randomised clinical trials (2007) Dement Geriatr Cogn Disord, 24, pp. 20-27Atri, A., Shaughnessy, L.W., Locascio, J.J., Growdon, J.H., Long-term course and effectiveness of combination therapy in Alzheimer disease (2008) Alzheimer Dis Assoc Disord, 22, pp. 209-221Shua-Haim, J., Smith, J., Picard, F., Steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer's disease not affected by co-administration of memantine: An open-label, crossover, single-centre study (2008) Clin Drug Investig, 28, pp. 361-374Grossberg, G.T., Edwards, K.R., Zhao, Q., Rationale for combination therapy with galantamine and memantine in Alzheimer's disease (2006) J Clin Pharmacol, 46 (7 SUPPL. 1), pp. S17-S26Zhu, C.W., Livote, E.E., Kahle-Wrobleski, K., (2010) Longitudinal medication usage in Alzheimer disease patients, , Alzheimer Dis Assoc Disord Jul 9McShane, R., Areosa, S.A.N.M., Memantine for dementia (2011) Cochrane Database of Systematic Reviews, p. 003154Peskind, E.R., Potkin, S.G., Pomara, N., Memantine treatment in mild to moderate Alzheimer disease: A 24-week randomized, controlled trial (2006) Am J Geriatr Psychiatry, 14, pp. 704-715Porsteinsson, A.P., Grossberg, G.T., Mintzer, J., Olin, J.T., Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: A randomized, double-blind, placebo-controlled trial (2008) Curr Alzheimer Res, 5, pp. 83-89. , Memantine MEM-MD-12 Study GroupDoody, R.S., Tariot, P.N., Pfeiffer, E., Olin, J.T., Graham, S.M., Meta-analysis of six-month memantine trials in Alzheimer's disease (2007) Alzheimers Dement, 3, pp. 7-17Schneider, L.S., Commentary on "Meta-analysis of six-month memantine trials in Alzheimer's disease. " Wuthering forest plots: Distinguishing the forest from the plots (2007) Alzheimers Dement, 3, pp. 18-20Knopman, D.S., Commentary on "Meta-analysis of six-month memantine trials in Alzheimer's disease. " Memantine has negligible benefits in mild to moderate Alzheimer's disease (2007) Alzheimers Dement, 3, pp. 21-22Schneider, L.S., Insel, P.S., Weiner, M.W., Treatment with cholinesterase inhibitors and memantine of patients in the Alzheimer's Disease Neuroimaging Initiative (2011) Arch Neurol, 68, pp. 58-66. , Alzheimer's Disease Neuroimaging InitiativeLuo, Y., Smith, J.V., Paramasivam, V., Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761 (2002) Proc Natl Acad Sci U S A, 99, pp. 12197-202Smith, J.V., Luo, Y., Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761 (2003) J Alzheimers Dis, 5, pp. 287-300Mix, J.A., Crews Jr., W.D., A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: Neuropsychological findings (2002) Hum Psychopharmacol, 17, pp. 267-277Birks, J., Evans, G., Ginkgo biloba for cognitive impairment and dementia (2009) Cochrane Database Syst Rev, (1), pp. CD003120Dodge, H.H., Zitzelberger, T., Oken, B.S., Howieson, D., Kaye, J., A randomized placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline (2008) Neurology, 70, pp. 1809-1817de Kosky, S.T., Williamson, J.D., Fitzpatrick, A.L., Ginkgo biloba for prevention of dementia: A randomized controlled trial (2008) JAMA, 300, pp. 2253-2262. , Ginkgo Evaluation of Memory (GEM) Study InvestigatorsSnitz, B.E., O'Meara, E.S., Carlson, M.C., Ginkgo biloba for preventing cognitive decline in older adults: A randomized trial (2009) JAMA, 302, pp. 2663-2670. , Ginkgo Evaluation of Memory (GEM) Study InvestigatorsBerman, K., Brodaty, H., Tocopherol (vitamin E) in Alzheimer's disease and other neurodegenerative disorders (2004) CNS Drugs, 18, pp. 807-825Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Wilson, R.S., Vitamin E and cognitive decline in older persons (2002) Arch Neurol, 59, pp. 1125-1132Sano, M., Ernesto, C., Thomas, R.G., A controlled trial of selegiline, alphatocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's disease Cooperative Study (1997) N Engl J Med, 336, pp. 1216-1222Petersen, R.C., Thomas, R.G., Grundman, M., Vitamin E and donepezil for the treatment of mild cognitive impairment (2005) N Engl J Med, 352, pp. 2379-2388. , Alzheimer's Disease Cooperative Study GroupIsaac, M.G., Quinn, R., Tabet, N., Vitamin E for Alzheimer disease and mild cognitive impairment (2008) Cochrane Database Syst Rev, (3), pp. CD002854Miller III, E.R., Pastor-Barriuso, R., Dalal, D., Riemersma, R.A., Appel, L.J., Guallar, E., Meta-analysis: High dosage vitamin E supplemention may increase all-cause mortality (2005) Ann Intern Med, 142, pp. 37-46Dysken, M.W., Kirk, L.N., Kuskowski, M., Changes in vitamin E prescribing for Alzheimer patients (2009) Am J Geriatr Psychiatry, 17, pp. 621-624Birks, J., Flicker, L., Selegiline for Alzheimer's disease (2003) Cochrane Database Syst Rev, (1). , CD000442Irving, G.F., Freund-Levi, Y., Eriksdotter-Jönhagen, M., Omega-3 Fatty Acid Supplementation Effects on Weight and Appetite in Patients with Alzheimer's Disease: The omega-3 Alzheimer's Disease Study (2009) J Am Geriatr Soc, 57, pp. 11-17Lim, W.S., Gammack, J.K., van Niekerk, J., Dangour, A.D., Omega 3 fatty acid for the prevention of dementia (2006) Cochrane Database Syst Rev, (1). , CD005379Freund-Levi, Y., Basun, H., Cederholm, T., Omega-3 supplementation in mild to moderate Alzheimer's disease: Effects on neuropsychiatric symptoms (2008) Int J Geriatr Psychiatry, 23, pp. 161-169Dangour, A.D., Whitehouse, P.J., Rafferty, K., B-vitamins and fatty acids in the prevention and treatment of Alzheimer's disease and dementia: A systematic review (2010) J Alzheimers Dis, 22, pp. 205-224Aisen, P.S., Schneider, L.S., Sano, M., High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial (2008) JAMA, 300, pp. 1774-1783. , Alzheimer Disease Cooperative StudyFord, A.H., Flicker, L., Alfonso, H., Vitamins B(12), B(6), and folic acid for cognition in older men (2010) Neurology, 75, pp. 1540-1547Malouf, R., Grimley Evans, J., Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people (2008) Cochrane Database Syst Rev, (4). , CD004514Henderson, V.W., Paganini-Hill, A., Miller, B.L., Estrogen for Alzheimer's disease in women: Randomized, double-blind, placebo-controlled trial (2000) Neurology, 54, pp. 295-301Mulnard, R.A., Cotman, C.W., Kawas, C., Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: A randomized controlled trial. Alzheimer's disease Cooperative Study (2000) JAMA, 283, pp. 1007-1015Shumaker, S.A., Legault, C., Rapp, S.R., Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: The Women's Health Initiative Memory Study: A randomized controlled trial (2003) JAMA, 289, pp. 2651-2662. , WHIMS InvestigatorsShumaker, S.A., Legault, C., Kuller, L., Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study (2004) JAMA, 291, pp. 2947-2958. , Women's Health Initiative Memory StudyHenderson, V.W., Estrogen-containing hormone therapy and Alzheimer's disease risk: Understanding discrepant inferences from observational and experimental research (2006) Neuroscience, 138, pp. 1031-1039Sano, M., Jacobs, D., Andrews, H., A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer's disease and loss of memory in women: Design and baseline characteristics (2008) Clin Trials, 5, pp. 523-533Veld, B.A., Ruitenberg, A., Hofman, A., Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease (2001) N Engl J Med, 345, pp. 1515-1521Aisen, P.S., Schafer, K.A., Grundman, M., Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: A randomized controlled trial (2003) JAMA, 289, pp. 2819-2826. , Alzheimer's Disease Cooperative StudyTabet, N., Feldmand, H., Ibuprofen for Alzheimer's disease (2003) Cochrane Database Syst Rev, (2). , CD004031de Jong, D., Jansen, R., Hoefnagels, W., No effect of one-year treatment with indomethacin on Alzheimer's disease progression: A randomized controlled trial (2008) PLoS One, 3, pp. e1475Martin, B.K., Szekely, C., Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a randomized, controlled trial of naproxen and celecoxib (2008) Arch Neurol, 65, pp. 896-905. , ADAPT Research GroupLi, G., Higdon, R., Kukull, W.A., Statin therapy and risk of dementia in the elderly: A community-based prospective cohort study (2004) Neurology, 63, pp. 1624-1628Zamrini, E., McGwin, G., Roseman, J.M., Association between statin use and Alzheimer's disease (2004) Neuroepidemiology, 23, pp. 94-98Zhou, B., Teramukai, S., Fukushima, M., Prevention and treatment of dementia or Alzheimer's disease by statins: A meta-analysis (2007) Dement Geriatr Cogn Disord, 23, pp. 194-201Feldman, H.H., Doody, R.S., Kivipelto, M., Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe (2010) Neurology, 74, pp. 956-964. , LEADe InvestigatorsMcGuinness, B., O'Hare, J., Craig, D., Bullock, R., Malouf, R., Passmore, P., Statins for the treatment of dementia (2010) Cochrane Database Syst Rev, (8). , CD007514van Paasschen, J., Clare, L., Woods, R.T., Linden, D.E., Can we change brain functioning with cognition-focused interventions in Alzheimer's disease? 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(2006) Neuropsychol Rehabil, 16, pp. 505-536Rothi, L.J., Fuller, R., Leon, S.A., Errorless practice as a possible adjuvant to donepezil in Alzheimer's disease (2009) J Int Neuropsychol Soc, 15, pp. 311-322Yu, F., Rose, K.M., Burgener, S.C., Cognitive training for early-stage Alzheimer's disease and dementia (2009) J Gerontol Nurs, 35, pp. 23-29Hogan, D.B., Bailey, P., Black, S., Diagnosis and treatment of dementia: Nonpharmacologic and pharmacologic therapy for mild to moderate dementia (2008) CMAJ, 179, pp. 1019-1026Heyn, P., Abreu, B.C., Ottenbacher, K.J., The effects of exercise training on elderly persons with cognitive impairment and dementia: A meta-analysis (2004) Arch Phys Med Rehabil, 85, pp. 1694-1704Lautenschlager, N.T., Cox, K., Kurz, A.F., Physical activity and mild cognitive impairment and Alzheimer's disease (2010) Curr Neurol Neurosci Rep, 10, pp. 352-358Forbes, D., Forbes, S., Morgan, D.G., Markle-Reid, M., Wood, J., Culum, I., Physical activity programs for persons with dementia (2008) Cochrane Database Syst Rev, (3). , CD006489Rolland, Y., Pillard, F., Klapouszczak, A., Exercise program for nursing home residents with Alzheimer's disease: A 1-year randomized, controlled trial (2007) J Am Geriatr Soc, 55, pp. 158-165Apostolova, L.G., Cummings, J.L., Neuropsychiatric manifestations in mild cognitive impairment: A systematic review of the literature (2008) Dement Geriatr Cogn Disord, 25, pp. 115-126Fillit, H.M., The pharmacoeconomics of Alzheimer's disease (2000) Am J Manag Care, 6 (22 SUPPL.), pp. S1139-S1144Buhr, G.T., White, H.K., Difficult behaviors in long-term care patients with dementia (2006) J Am Med Dir Assoc, 7, pp. 180-192(2007) Interpretive guidelines for long-term care facilities, , Department of Health and Human Services, State Operations Manual, Appendix PP-Guidance to Surveyors for Long Term Care Facilities, Accessed August 21 cms.hhs.gov/manuals/downloads/som107_pp_guidelines_ltcf.pdfShekelle, P., Maglione, M., Bagley, S., (2007) Comparative effectiveness of off-label use of atypical antipsychotics. 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Treatment Of Alzheimer's Disease In Brazil: I. Cognitive Disorders [tratamento Da Doença De Alzheimer No Brasil: I. Dos Transtornos Cognitivos]

This article reports the recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the treatment of Alzheimer's disease (AD) in Brazil, with special focus on cognitive disorders. It constitutes a revision and broadening of the 2005 guidelines based on a consensus involving researchers (physicians and non-physicians) in the field. The authors carried out a search of articles published since 2005 on the MEDLINE, LILACS and Cochrane Library databases. The search criteria were pharmacological and non-pharmacological treatment of cognitive disorders in AD. Studies retrieved were categorized into four classes, and evidence into four levels, based on the 2008 recommendations of the American Academy of Neurology. The recommendations on therapy are pertinent to the dementia phase of AD. Recommendations are proposed for the treatment of cognitive disorders encompassing both pharmacological (including acetyl-cholinesterase inhibitors, memantine and other drugs and substances) and non-pharmacological (including cognitive rehabilitation, physical activity, occupational therapy, and music therapy) approaches. Recommendations for the treatment of behavioral and psychological symptoms of dementia due to Alzheimer's disease are included in a separate article of this edition.53178188Engelhardt, E., Brucki, S.M., Cavalcanti, J.L., Forlenza, O.V., Laks, J., Vale, F.A., Treatment of Alzheimer's disease: Recommendations and suggestions of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2005) Arq Neuropsiquiatr., 63, pp. 1104-1112Gronseth, G., French, J., Practice parameters and technology assessments: What they are, what they are not, and why you should care (2008) Neurology, 71, pp. 1639-1643French, J., Gronseth, G., Lost in a jungle of evidence: We need a compass (2008) Neurology, 71, pp. 1634-1638McKhann, G.M., Knopman, D.S., Chertkow, H., The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup (2011) Alzheimers Dement, 7, pp. 263-269McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., Stadlan, E.M., Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDAWork Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease (1984) Neurology, 34, pp. 939-944Albert, M.S., Dekosky, S.T., Dickson, D., The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging and Alzheimer's Association workgroup (2011) Alzheimers Dement, 7, pp. 270-279Sperling, R.A., Aisen, P.S., Beckett, L.A., Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup (2011) Alzheimers Dement., 7, pp. 280-292Nordberg, A., Nicotinic receptor abnormalities of Alzheimer's disease: Therapeutic implications (2001) Biol Psychiatry, 49, pp. 200-210Peters, B.H., Levin, H.S., Effects of physostigmine and lecitin on memory in Alzheimer's disease (1979) Ann Neurol, 6, pp. 219-221Sumers, W.K., Majovski, L.V., Marsh, G.M., Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type (1986) N Eng J Med, 315, pp. 1241-1245Corey-Bloom, J., Anand, R., Veach, J., A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetyl-chonesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease (1998) Int. J Geriatr Psychopharmacol, 1, pp. 55-65Rogers, S.L., Farlow, M., Mohs, R., A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease (1998) Neurology, 50, pp. 136-145Raskind, M.A., Perskind, E.R., Wessel, T., Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension (2000) Neurology, 554, pp. 2261-2268Hansen, R.A., Gartlehner, G., Webb, A.P., Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: A systematic review and meta-analysis (2008) Clin Interv Aging, 3, pp. 211-225Lockhart, I.A., Mitchell, S.A., Kelly, S., Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer's disease: Systematic review of the "real-world" (2009) Dem Geriat Cog Dis, 28, pp. 389-403Winblad, B., Gauthier, S., Scinto, L., Safety and efficacy of galantamine in subjects with mild cognitive impairment (2008) Neurology, 70, pp. 2024-2035Burns, A., Bernabei, R., Bullock, R., Safety and efficacy of galantamine (Reminyl) in severe Alzheimer's disease (the CERAD study): A randomized, placebo-controlled, double-blind trial (2009) Lancet Neurol, 8, pp. 39-47Farlow, M., Grossberg, G.T., Meng, X., Rivastigmine transdermal patch and capsule in Alzheimer's disease: Influence of disease stage on response to therapy (2010) Int J Geriatr Psychiatry, , Dec;23. [Epub ahead of print]Winblad, B., Black, S.E., Homma, A., Donepezil treatment in severe Alzheimer's disease: A pooled analysis of three clinical trials (2009) Curr Med Res Opin, 25, pp. 2577-2587Jarvis, B., Figgitt, D.P., Memantine (2003) Drugs Aging, 20, pp. 465-476. , discussion 77-78Reisberg, B., Doody, R., Stoffler, A., Schmitt, F., Ferris, S., Mobius, H.J., Memantine in moderate-to-severe Alzheimer's disease (2003) N Engl J Med., 348, pp. 1333-1341Tariot, P.N., Farlow, M.R., Grossberg, G.T., Graham, S.M., McDonald, S., Gergel, I., Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial (2004) JAMA, 291, pp. 317-324Winblad, B., Jones, R.W., Wirth, Y., Stoffler, A., Mobius, H.J., Memantine in moderate to severe Alzheimer's disease: A meta-analysis of randomised clinical trials (2007) Dement Geriatr Cogn Disord, 24, pp. 20-27Atri, A., Shaughnessy, L.W., Locascio, J.J., Growdon, J.H., Long-term course and effectiveness of combination therapy in Alzheimer disease (2008) Alzheimer Dis Assoc Disord, 22, pp. 209-221Shua-Haim, J., Smith, J., Picard, F., Steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer's disease not affected by co-administration of memantine: An open-label, crossover, single-centre study (2008) Clin Drug Investig., 28, pp. 361-374Grossberg, G.T., Edwards, K.R., Zhao, Q., Rationale for combination therapy with galantamine and memantine in Alzheimer's disease (2006) J Clin Pharmacol, 46 (7 SUPPL. 1), pp. 17S-26SZhu, C.W., Livote, E.E., Kahle-Wrobleski, K., Longitudinal Medication Usage in Alzheimer Disease Patients (2010) Alzheimer Dis Assoc Disord., , Jul 9. [Epub ahead of print]McShane, R., Areosa, S.A., N. M. Memantine for dementia (2011) Cochrane Database of Systematic Reviews, (3), pp. CD003154Peskind, E.R., Potkin, S.G., Pomara, N., Memantine treatment in mild to moderate Alzheimer disease: A 24-week randomized, controlled trial (2006) Am J Geriatr Psychiatry., 14, pp. 704-715Porsteinsson, A.P., Grossberg, G.T., Mintzer, J., Olin, J.T., Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: A randomized, double-blind, placebo-controlled trial (2008) Curr Alzheimer Res, 5, pp. 83-89Doody, R.S., Tariot, P.N., Pfeiffer, E., Olin, J.T., Graham, S.M., Meta-analysis of six-month memantine trials in Alzheimer's disease (2007) Alzheimers Dement, 3, pp. 7-17Schneider, L.S., Commentary on "Meta-analysis of six-month memantine trials in Alzheimer's disease. " Wuthering forest plots: Distinguishing the forest from the plots (2007) Alzheimers Dement, 3, pp. 18-20Knopman, D.S., Commentary on "Meta-analysis of six-month memantine trials in Alzheimer's disease. " Memantine has negligible benefits in mild to moderate Alzheimer's disease (2007) Alzheimers Dement, 3, pp. 21-22Schneider, L.S., Insel, P.S., Weiner, M.W., Treatment with cholinesterase inhibitors and memantine of patients in the Alzheimer's Disease Neuroimaging Initiative (2011) Arch Neurol, 68, pp. 58-66Luo, Y., Smith, J.V., Paramasivam, V., Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761 (2002) Proc Natl Acad Sci, 99, pp. 12197-12202Smith, J.V., Luo, Y., Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761 (2003) J Alzheimer's Dis, 5, pp. 287-300Mix, J.A., Crews Jr., W.D., A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: Neuropsychological findings (2002) Hum Psychopharmacol, 17, pp. 267-277Birks, J., Evans, G., Ginkgo biloba for cognitive impairment and dementia (2009) Cochrane Database Syst Rev, (1), pp. CD003120. , Jan 21Dodge, H.H., Zitzelberger, T., Oken, B.S., A randomized placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline (2008) Neurology, 70, pp. 1809-1817DeKosky, S.T., Williamson, J.D., Annette, L., Ginkgo biloba for Prevention of Dementia: A Randomized Controlled Trial (2008) JAMA, 300, pp. 2253-2262Snitz, B.E., O'Meara, E.S., Carlson, M.C., Ginkgo biloba for Preventing Cognitive Decline in Older Adults: A Randomized Trial (2009) JAMA, 302, pp. 2663-2670Berman, K., Brodaty, H., Tocopherol (vitamin E) in Alzheimer's disease and other neurodegenerative disorders (2004) CNS Drugs, 18, pp. 807-825Morris, M.C., Evans, D.A., Bienias, J.L., Vitamin E and cognitive decline in older persons (2002) Arch Neurol, 59, pp. 1125-1132Sano, M., Ernesto, C., Thomas, R.G., A controlled trial of selegiline, alphatocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study (1997) N Engl J Med, 336, pp. 1216-1222Petersen, R.C., Thomas, R.G., Grundman, Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment (2005) N Engl J Med, 352, pp. 2379-2388Isaac, M.G., Quinn, R., Tabet, N., Vitamin E for Alzheimer disease and mild cognitive impairment (2008) Cochrane Database Syst Rev, 3, pp. CD002854Miller III, E.R., Pastor-Barriuso, R., Dalal, D., Meta-analysis: High dosage vitamin E supplemention may increase all-cause mortality (2005) Ann Intern Med, 142, pp. 37-46Dysken, M.W., Kirk, L.N., Kuskowski, M., Changes in vitamin E prescribing for Alzheimer patients (2009) Am J Geriatr Psychiatry., 17, pp. 621-624Birks, J., Flicker, L., Selegiline for Alzheimer's disease (2003) Cochrane Database Syst Rev, 1, pp. CD000442Faxén-Irving, G., Freund-Levi, Y., Eriksdotter-Jönhagen, M., Basun, H., Omega-3 Fatty Acid Supplementation Effects on Weight and Appetite in Patients with Alzheimer's Disease: The Omega-3 Alzheimer's Disease Study (2009) J Am Geriatr Soc, 57, pp. 11-17Lim, W.S., Gammack, J.K., van Niekerk, J.K., Dangour, A., Omega 3 fatty acid for the prevention of dementia (2006) Cochrane Database Syst Rev, 1, pp. CD005379Freund-Levi, Y., Basun, H., Cederholm, T., Faxén-Irving, G., Omega-3 supplementation in mild to moderate Alzheimer's disease: Effects on neuropsychiatric symptoms (2008) Int J Geriatr Psychiatry, 23, pp. 161-169Dangour, A.D., Whitehouse, P.J., Rafferty, K., B-vitamins and fatty acids in the prevention and treatment of Alzheimer's disease and dementia: A systematic review (2010) J Alzheimers Dis, 22, pp. 205-224Aisen, P.S., Schneider, L.S., Sano, M., Alzheimer Disease Cooperative Study. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial (2008) JAMA, 300, pp. 1774-1783Ford, A.H., Flicker, L., Alfonso, H., Vitamins B(12), B(6), and folic acid for cognition in older men (2010) Neurology, 75, pp. 1540-1547Malouf, R., Grimley Evans, J., Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people (2008) Cochrane Database Syst Rev, 4, pp. CD004514Henderson, V.W., Paganini-Hill, A., Miller, B.L., Estrogen for Alzheimer's disease in women: Randomized, double-blind, placebo-controlled trial (2000) Neurology, 54, pp. 295-301Mulnard, R.A., Cotman, C.W., Kawas, C., Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: A randomized controlled trial. Alzheimer's Disease Cooperative Study (2000) JAMA, 283, pp. 1007-1015Shumaker, S.A., Legault, C., Rapp, S.R., Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: The Women's Health Initiative Memory Study: A randomized controlled trial (2003) JAMA, 289, pp. 2651-2662Shumaker, S.A., Legault, C., Kuller, L., Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study (2004) JAMA, 291, pp. 2947-2958Henderson, V.W., Estrogen-containing hormone therapy and Alzheimer's disease risk: Understanding discrepant inferences from observational and experimental research (2006) Neuroscience., 138, pp. 1031-1039Sano, M., Jacobs, D., Andrews, H., A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer's disease and loss of memory in women: Design and baseline characteristics (2008) Clin Trials, 5, pp. 523-533Veld, B.A., Ruitenberg, A., Hofman, A., Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease (2001) N Engl J Med, 345, pp. 1515-1521Aisen, P.S., Schafer, K.A., Grundman, M., Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: A randomized controlled trial (2003) JAMA, 289, pp. 2819-2826Tabet, N., Feldmand, H., Ibuprofen for Alzheimer's disease (2003) Cochrane Database Syst Rev, 2, pp. CD004031de Jong, D., Jansen, R., Hoefnagels, W., No effect of one-year treatment with indomethacin on Alzheimer's disease progression: A randomized controlled trial (2008) PLoS One., 3, pp. e1475Martin, B.K., Szekely, C., Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a randomized, controlled trial of naproxen and celecoxib (2008) Arch Neurol., 65, pp. 896-905. , ADAPT Research GroupLi, G., Higdon, R., Kukull, W.A., Statin therapy and risk of dementia in the elderly: A community-based prospective cohort study (2004) Neurology, 63, pp. 1624-1628Zamrini, E., McGwin, G., Roseman, J.M., Association between statin use and Alzheimer's disease (2004) Neuroepidemiology, 23, pp. 94-98Zhou, B., Teramukai, S., Fukushima, M., Prevention and treatment of dementia or Alzheimer's disease by statins: A meta-analysis (2007) Dement Geriatr Cogn Disord, 23, pp. 194-201Feldman, H.H., Doody, R.S., Kivipelto, M., Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe (2010) Neurology, 74, pp. 956-964McGuinness, B., O'Hare, J., Craig, D., Bullock, R., Malouf, R., Passmore, P., Statins for the treatment of dementia (2010) Cochrane Database Syst Rev., (8), pp. CD007514. , Aug 4van Paasschen, J., Clare, L., Woods, R.T., Linden, D.E., Can we change brain functioning with cognition-focused interventions in Alzheimer's disease? The role of functional neuroimaging (2009) Restor Neurol Neurosci, 27, pp. 473-491Chapman, S.B., Weiner, M.F., Rackley, A., Hynan, L.S., Zientz, J., Effects of cognitive-communication stimulation for Alzheimer's disease patients treated with donepezil (2004) J Speech Lang Hear Res, 47, pp. 1149-1163Requena, C., Maestú, F., Campo, P., Fernández, A., Ortiz, T., Effects of cholinergic drugs and cognitive training on dementia: 2-year follow-up (2006) Dement Geriatr Cogn Disord, 22, pp. 339-345Olazarán, J., Reisberg, B., Clare, L., Nonpharmacological Therapies in Alzheimer's Disease: A Systematic Review of Efficacy (2010) Dement Geriatr Cogn Disord, 30, pp. 161-178Cotelli, M., Calabria, M., Zanetti, O., Cognitive rehabilitation in Alzheimer's disease (2006) Aging Clin Exp Res, 18, pp. 141-143Onder, G., Zanetti, O., Giacobini, E., Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease: Randomised controlled trial (2005) Br J Psychiatry, 187, pp. 450-455Yamaguchi, H., Maki, Y., Yamagami, T., Overview of non-pharmacological intervention for dementia and principles of brain-activating rehabilitation (2010) Psychogeriatrics, 10, pp. 206-213Haslam, C., Gilroy, D., Black, S., Beesley, T., How successful is errorless learning in supporting memory for high and low-level knowledge in dementia? 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Treatment Of Alzheimer's Disease In Brazil: Ii. Behavioral And Psychological Symptoms Of Dementia [tratamento Da Doença De Alzheimer No Brasil: Ii. Dos Sintomas Comportamentais E Psicológicos Da Demência]

This article reports the recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the treatment of Alzheimer's disease (AD) in Brazil, with special focus on behavioral and psychological symptoms of dementia (BPSD). It constitutes a revision and broadening of the 2005 guidelines based on a consensus involving researchers (physicians and non-physicians) in the field. The authors carried out a search of articles published since 2005 on the MEDLINE, LILACS and Cochrane Library databases. The search criteria were pharmacological and non-pharmacological treatment of the behavioral and psychological symptoms of AD. Studies retrieved were categorized into four classes, and evidence into four levels, based on the 2008 recommendations of the American Academy of Neurology. The recommendations on therapy are pertinent to the dementia phase of AD. Recommendations are proposed for the treatment of BPSD encompassing both pharmacological (including acetyl-cholinesterase inhibitors, memantine, neuroleptics, anti-depressives, benzodiazepines, anti-convulsants plus other drugs and substances) and non-pharmacological (including education-based interventions, physiotherapy, occupational therapy, music therapy, therapy using light, massage and art therapy) approaches. Recommendations for the treatment of cognitive disorders of AD symptoms are included in a separate article of this edition.53189197Engelhardt, E., Brucki, S.M., Cavalcanti, J.L., Forlenza, O.V., Laks, J., Vale, F.A., Treatment of Alzheimer's disease: Recommendations and suggestions of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2005) Arq Neuropsiquiatr, 63, pp. 1104-1112Gronseth, G., French, J., Practice parameters and technology assessments: What they are, what they are not, and why you should care (2008) Neurology, 71, pp. 1639-1643French, J., Gronseth, G., Lost in a jungle of evidence: We need a compass (2008) Neurology, 71, pp. 1634-1638McKhann, G.M., Knopman, D.S., Chertkow, H., The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup (2011) Alzheimers Dement, 7, pp. 263-269McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., Stadlan, E.M., Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDAWork Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease (1984) Neurology, 34, pp. 939-944Albert, M.S., Dekosky, S.T., Dickson, D., The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging and Alzheimer's Association workgroup (2011) Alzheimers Dement, 7, pp. 270-279Sperling, R.A., Aisen, P.S., Beckett, L.A., Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup (2011) Alzheimers Dement, 7, pp. 1-13Apostolova, L.G., Cummings, J.L., Neuropsychiatric manifestations in mild cognitive impairment: A systematic review of the literature (2008) Dement Geriatr Cogn Disord, 25, pp. 115-126Fillit, H.M., The pharmacoeconomics of Alzheimer's disease (2000) Am J Manag Care., 6 (22 SUPPL.), pp. S1139-S1144Buhr, G.T., White, H.K., Difficult behaviors in long-term care patients with dementia (2006) J Am Med Dir Assoc, 7, pp. 180-192Interpretive guidelines for long-term care facilities, , cms.hhs.gov/manuals/downloads/som107_pp_guidelines_ltcf.pdf, Department of Health and Human Services, State Operations Manual, Appendix PP-Guidance to Surveyors for Long Term Care Facilities, Accessed August 21, 2007Shekelle, P., Maglione, M., Bagley, S., Comparative effectiveness of off-label use of atypical antipsychotics (2007) Comparative Effectiveness Review, , Effectivehealthcare.ahrq.gov/repFiles/Atypical_Antipsychotics_Final_Report.pdf, No. 6. 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Boston, MA: Butterworth-HeinemannLyketsos, C.G., Colenda, C.C., Beck, C., Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer disease (2006) Am J Geriatr Psychiatry, 14, pp. 561-572Ballard, C.G., Thomas, A., Fossey, J., A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: The neuropsychiatric inventory median cutoff is a predictor of clinical outcome (2004) J Clin Psychiatry, 65, pp. 114-119Ballard, C., Lana, M.M., Theodoulou, M., A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial) (2008) PLoS Med, 5, pp. e76Sink, K.M., Holden, K.F., Yaffe, K., Pharmacologic treatment of neuropsychiatric symptoms of dementia: A review of the evidence (2005) JAMA, 293, pp. 596-608de Deyn, P.P., Katz, I.R., Brodaty, H., Lyons, B., Greenspan, A., Burns, A., Management of agitation, aggression, and psychosis associated with dementia: A pooled analysis including three randomized, placebo-controlled double blind trials in nursing home residents treated with risperidone (2005) Clin Neurol Neurosurg, 107, pp. 497-508Katz, I., de Deyn, P.P., Mintzer, J., Greenspan, A., Zhu, Y., Brodaty, H., The efficacy and safety of risperidone in the treatment of psychosis of Alzheimers disease and mixed dementia: A meta-analysis of 4 placebo controlled clinical trials (2007) Int J Geriatr Psychiatry, 22, pp. 475-484Schneider, L.S., Dagerman, K.S., Insel, P., Risk of death with atypical antipsychotic drug treatment for dementia: Meta-analysis of randomized placebo-controlled trials (2005) JAMA, 294, pp. 1934-1943Sink, K.M., Holden, K.F., Yaffe, K., Pharmacological treatment of neuropsychiatric symptoms of dementia: A review of the evidence (2005) JAMA, 293, pp. 596-608Guidelines abstracted from the American Academy of Neurology's dementia guidelines for early detection, diagnosis and management of dementia (2003) J Am Geriatr Soc, 51, pp. 869-873. , AGS Clinical Practice Committee(2005) AAGP Atypical Position Statement, , http://www.aagponline.org/prof/antipsychstat_0705.asp, American Academy for Geriatric Psychiatry, Retrieved March 26, 2008, fromMadhusoodanan, S., Shah, P., Brenner, R., Gupta, S., Pharmacological treatment of the psychosis of Alzheimer's Disease: What is the best approach? (2007) CNS Drugs, 21, pp. 101-115Trinh, N., Hoblyn, J., Mohanty, S., Yaffe, K., Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease a meta-analysis (2003) JAMA, 289, pp. 210-216Loy, C., Schneider, L., Galantamine for Alzheimer's disease and mild cognitive impairment. Cochrane Database of Systematic Reviews (2011) In: The Cochrane Library, 4. , Art. No. CD001747Cummings, J.L., Schneider, L., Tariot, P.N., Kershaw, P.R., Yuan, W., Reduction of behavioral disturbances and caregivers distress by galantamine in patients with Alzheimer's disease (2004) Am J Psychiatry, 161, pp. 532-538Birks, J., Grimley, E.J., Iakovidou, V., Tsolaki, M., Rivastigmine for Alzheimer's disease. Cochrane Database of Systematic Reviews (2011) In: The Cochrane Library, 4. , Art. No. CD001191Birks, J., Harvey, R., Donepezil for dementia due to Alzheimer's disease. Cochrane Database of Systematic Reviews (2011) In: The Cochrane Library, 4. , Art. No. CD001190Gauthier, S., Feldman, H., Hecker, J., Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease (2002) Int Psychogeriatrics, 14, pp. 389-404Feldman, H., Gauthier, S., Hecker, J., Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: A subgroup analysis from a randomized, placebo-controlled trial (2005) Int J Geriatric Psychiatry, 20, pp. 559-569Holmes, C., Wilkinson, D., Dean, C., The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease (2004) Neurology, 63, pp. 214-219Howard, R.J., Juszczak, E., Ballard, C.G., Donepesil for the treatment of agitation in Alzheimer's disease (2007) N Engl J Med, 357, pp. 1382-1392McShane, R., Areosa, S.A., N. M. Memantine for dementia (2011) Cochrane Database of Systematic Reviews, (3), pp. CD003154Tariot, P.N., Farlow, M.R., Grossberg, G.T., Graham, S.M., McDonald, S., Gergel, I., Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial (2004) JAMA, 291, pp. 317-324Cummings, J.L., Schneider, E., Tariot, P.N., Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment (2006) Neurology, 67, pp. 57-63Konovalov, S., Muralle, S., Tampi, R.R., Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: A literature review (2008) Int Psychogeriatrics, 20, pp. 293-308Tariot, P.N., Erb, R., Podgorski, C.A., Efficacy and tolerability of carbamazepine for agitation and aggression in dementia (1998) Am J Psychiatry, 155, pp. 54-61Seitz, D., Adunuri, N., Gill, S.S., Antidepressants for agitation and psychosis in dementia. 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No. CD008191Weintraub, D., Rosenberg, P.B., Drye, L.T., Sertraline for the treatment of depression in Alzheimer's disease: Week-24 outcomes (2010) Am J Geriatr Psychiatry, 18, pp. 332-340Lyketsos, C.G., DelCampo, L., Steinberg, M., Treating depression in Alzheimer disease (2003) Arch Gen Psychiatry, 60, pp. 737-746Finkel, S.I., Mintzer, J.E., Dysken, M., A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil (2004) Int J Geriatric Psychiatry, 19, pp. 9-18Nyth, A.L., Gerhard, G., The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders: A Nordic multicenter study (1990) Br J Psychiatry, 157, pp. 894-901Pollock, B.G., Mulsant, B.H., Rosen, J., Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients (2002) Am J Psychiatry, 159, pp. 460-465Suktzer, D.L., Gray, K.F., Gunay, I., Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia? (2001) J Am Geriatrics Society, 49, pp. 1294-1300Barak, Y., Plopski, I., Tadger, S., Paleacu, D., Escitalopram versus risperidone for the treatment of behavioral and psychotic symptoms associated with Alzheimer's disease: A randomized double-blind pilot study (2011) Int Psychogeriatrics, 15, pp. 1-5Chibnall, J.T., Tait, R.C., Harman, B., Luebbert, R.A., Effect of acetaminophen on behavior, well-being, and psychotropic medication use in nursing home residents with moderate-to-severe dementia (2005) J Am Geriatrics Society, 53, pp. 1921-1929Lu, P.H., Masterman, D.A., Mulnard, R., Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and health elderly men (2006) Arch Neurol, 63, pp. 177-185Gehrman, P.R., Connor, D.J., Martin, J.L., Melatonin fails to improve sleep or agitation in a double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer's disease (2009) Am J Geriatr Psychiatry, 17, pp. 166-169Scripnikov, A., Khomeno, A., Napryeyenko, O., Effects of ginkgo biloba extract EGb 761 on neuropsychiatric symptoms of dementia: Findings from a randomized controlled trial (2007) Wien Med Wochenschr, 157, pp. 295-300Doody, R.S., Gavrilova, S.I., Sano, M., Effect od dimebon on cognition, activities of daily living, behavior, and global function in patients with mild-to-moderate Alzheimer's disease: A randomized, double blind, placebo-controlled study (2008) Lancet, 372, pp. 207-215Beer, C.D., Horner, B., Almeida, O.P., Dementia in residential care: Education intervention trial (DIRECT)protocol for a randomised controlled trial (2010) Trials, 11, p. 63Perry, M., Drašković, I., Achterberg, T., Can an EASYcare based dementia training programme improve diagnostic assessment and management of dementia by general practitioners and primary care nurses? 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Default Mode, Executive Function, And Language Functional Connectivity Networks Are Compromised In Mild Alzheimeŕs Disease

Alzheimer's disease (AD) is characterized by mental and cognitive problems, particularly with memory, language, visuospatial skills (VS), and executive functions (EF). Advances in the neuroimaging of AD have highlighted dysfunctions in functional connectivity networks (FCNs), especially in the memory related default mode network (DMN). However, little is known about the integrity and clinical significance of FNCs that process other cognitive functions than memory. We evaluated 22 patients with mild AD and 26 healthy controls through a resting state functional MRI scan. We aimed to identify different FCNs: the DMN, language, EF, and VS. Seed-based functional connectivity was calculated by placing a seed in the DMN (posterior cingulate cortex), language (Broca's and Wernicke's areas), EF (right and left dorsolateral prefrontal cortex), and VS networks (right and left associative visual cortex). We also performed regression analyses between individual connectivity maps for the different FCNs and the scores on cognitive tests. We found areas with significant decreases in functional connectivity in patients with mild AD in the DMN and Wernicke's area compared with controls. Increased connectivity in patients was observed in the EF network. Regarding multiple linear regression analyses, a significant correlation was only observed between the connectivity of the DMN and episodic memory (delayed recall) scores. In conclusion, functional connectivity alterations in mild AD are not restricted to the DMN. Other FCNs related to language and EF may be altered. 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