Abstracts
Oral infections may play a role in Alzheimer's disease (AD).
Objective
To describe the orofacial pain, dental characteristics and associated factors in patients with Alzheimer's Disease that underwent dental treatment.
Method
29 patients with mild AD diagnosed by a neurologist were included. They fulfilled the Mini Mental State Exam and Pfeffer's questionnaire. A dentist performed a complete evaluation: clinical questionnaire; research diagnostic criteria for temporomandibular disorders; McGill pain questionnaire; oral health impact profile; decayed, missing and filled teeth index; and complete periodontal investigation. The protocol was applied before and after the dental treatment. Periodontal treatments (scaling), extractions and topic nystatin were the most frequent.
Results
There was a reduction in pain frequency (p=0.014), mandibular functional limitations (p=0.011) and periodontal indexes (p<0.05), and an improvement in quality of life (p=0.009) and functional impairment due to cognitive compromise (p<0.001) after the dental treatment. Orofacial complaints and intensity of pain also diminished.
Conclusion
The dental treatment contributed to reduce co-morbidities associated with AD and should be routinely included in the assessment of these patients.
Alzheimer's disease; oral infections; orofacial pain; periodontal disease; dental treatment
Infecções orais podem ter um papel na doença de Alzheimer (DA).
Objetivo
Descrever as características orofaciais, dor, odontológicas e fatores associados em doentes com DA submetidos a tratamento dentário.
Método
29 doentes diagnosticados com DA por neurologista foram avaliados através do Mini Exame do Estado Mental e questionário Pfeffer. O exame odontológico foi realizado antes e depois do tratamento dentário e incluiu: questionário clínico; critérios diagnósticos de pesquisa para disfunção temporomandibular; questionário de dor McGill; protocolo de impacto de saúde oral; dentes cariados, perdidos e obturados; e avaliação periodontal. Os procedimentos mais frequentes foram raspagem periodontal, exodontias e prescrição de nistatina tópica.
Resultados
Houve uma redução na frequência de dor (p=0,014), limitações mandibulares (p=0,011), índices periodontais (p<0.05), e melhora na qualidade de vida (p=0,009) e no comprometimento funcional e cognitivo (p<0,001) após o tratamento dentário. Queixas orofaciais e intensidade de dor também diminuíram.
Conclusão
O tratamento dentário contribuiu para reduzir comorbidades associadas à DA e deveria ser incluído na rotina de avaliação desses pacientes.
doença de Alzheimer; infecções orais; dor orofacial; doença periodontal; tratamento dentário
In the last century the world population got older, and since then there has been a growing interest in maintaining health and an active and functional life in the third age. The frequency of elderly people with chronic diseases is high (20%-35%), and many of them are fragile (2%-10%)11 Freedman GM. Chronic pain: clinical management of common causes of geriatric pain. Geriatrics. 2002;57(5):36-41.. Neurodegenerative diseases cause severe morbidity, and among them Alzheimer's Disease (AD) are progressive and still do not have an effective treatment; therefore, there is an interest in preventing it, improving the quality of life of these patients and reducing the speed of progression22 David R, Piano J, Robert P. Treatment of behavioral disorders in Alzheimer's diseases. Rev Prat. 2011;61(7):939-44..
AD is the most common degenerative cerebral disease and the main cause of dementia in
Western countries (50%-66%)33 Scheltens PH, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P
et al. Atropht of medial temporal lobes on MRI in “probable”
Alzheimer’s disease an normal aging: diagnostics value and
neuropsychological correlates. J Neurol Neurosurg Psychiat. 1992;55(10):967-72.
http://dx.doi.org/10.1136/jnnp.55.10.967
https://doi.org/10.1136/jnnp.55.10.967...
. It
seriously interferes in personal, social and work activities of the patients44 Almeida OP, Nitrini R. Demência. São Paulo: Fundo
editorial BYK; 1995.. Its pathophysiology includes chronic
neuronal and inflammatory abnormalities55 Schwarz MJ, Chiang S, Müller N, Ackenheil M. T-helper-1 and
T-helper-2 responses in psychiatric disorders. Brain Behav Immun.
2001;15(4):340-70. http://dx.doi.org/10.1006/brbi.2001.0647
https://doi.org/10.1006/brbi.2001.0647...
, and dental infections are common in these patients66 Friedlander AH, Norman DC, Mahler ME, Norman KM, Yagiela JA.
Alzheimer's disease: psychopathology, medical management and dental
implications. J Am Dent Assoc. 2006;137(9):1240-51.
http://dx.doi.org/10.14219/jada.archive.2006.0381
https://doi.org/10.14219/jada.archive.20...
. These infections are not often
assessed during the treatment of AD but they need to be considered due to the risk of
dissemination and the severe complications that they might cause77 Aderhold l, Knothe; Frenkel G. The bacteriology of dentogenous
pyogenic infections. Oral Surg Oral Med Oral Pathol. 1981;52(6):583-7.
10.1016/0030-4220(81)90072-4
https://doi.org/10.1016/0030-4220(81)900...
. Besides, dental infections are a cause of orofacial
pain, which is a frequent complaint among the elderly. Despite recent evidence that oral
infections such as periodontitis may be associated with AD, to our knowledge no study
prior to this investigated the effects of dental treatment to patients with AD88 Kamer AR. Systemic inflammation and disease progression in Alzheimer
dsease. Neurology. 2010;74(14):1157-8.
http://dx.doi.org/10.1212/WNL.0b013e3181d5df7f
https://doi.org/10.1212/WNL.0b013e3181d5...
.
Thus, the objective of this study was to evaluate patients with AD before and after dental treatment about their orofacial characteristics, as well as emotional, functional and cognitive aspects.
METHOD
In this descriptive not controlled open study, 29 (twenty-nine) patients with mild AD
according to the diagnostic criteria of the National Institute for Communicative
Disorders and Stroke – Alzheimer’s Disease and Related Disorders
Association (NINCDS-ADRDA)99 Mckhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM.
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. Neurology. 1984;34(7):939-44.
http://dx.doi.org/10.1212/wnl.34.7.939
https://doi.org/10.1212/wnl.34.7.939...
were
evaluated. They had been observed by the Grupo de Neurologia Cognitiva e do
Comportamento (Hospital das Clínicas, Faculdade de Medicina, Universidade de
São Paulo). All patients / relatives / guardians were informed about the
purposes of the study and all signed the informed consent. The protocol was approved
by the local Ethics Committee. This study was supported by FAPESP (Foundation for
Research of the State of Sao Paulo – 2007/04930-1 and 2007/06852-8).
Exclusion criteria: moderate or severe dementia according to the NINCDS-ADRDA criteria. Diagnosis of other neurodegenerative or neuroendocrine diseases, neuroinfections.
Inclusion criteria: diagnosis of AD according to the
NINCDS-ADRDA99 Mckhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM.
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. Neurology. 1984;34(7):939-44.
http://dx.doi.org/10.1212/wnl.34.7.939
https://doi.org/10.1212/wnl.34.7.939...
, score between 18
and 26 by the Mini Mental State Exam (MMSE) characterizing mild AD1010 Brucki SMD, Nitrini R, Carameli P, Bertolucci PHF, Okamoto IH.
Sugestões para o uso do Mini Exame do Estado Mental no Brasil. Arq
Neuropsiquiatr. 2003;61(3B):777-81.
http://dx.doi.org/10.1590/s0004-282x2003000500014
https://doi.org/10.1590/s0004-282x200300...
. The diagnosis was performed by a
trained neurologist.
A dentist performed a complete orofacial assessment which included:
-
(i) Clinical questionnaire of orofacial pain, for the diagnosis of orofacial pain and oral infections, including a complete dental exam and the evaluation of the oral mucosa, tongue, and pain characteristics (location, intensity by the visual analogue scale – VAS, associated factors including tinnitus, bruxism, alleviating and worsening factors)1111 Siqueira SRDT, Nóbrega JCM, Valle LBS, Teixeira MJ, Siqueira JTT. Idiopathic trigeminal neuralgia: characteristics and dental procedures. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98(3):311-5. http://dx.doi.org/10.1016/S1079210404003191
https://doi.org/10.1016/S107921040400319... ; -
(ii) Research diagnostic criteria for temporomandibular disorders (RDC/TMD): diagnosis of TMD and evaluation of emotional and functional aspects related to the mandibular function1212 Lucena LB, Komisnky M, Costa LJ, Goes PS. Validation of the Portuguese version of the RDC/TMD Axis II questionnaire. Braz Oral Res. 2006;20(4):312-7. http://dx.doi.org/10.1590/s1806-83242006000400006
https://doi.org/10.1590/s1806-8324200600... ; -
(iii) McGill pain questionnaire for the assessment of the quality of pain1313 Pimenta CAM, Teixeira MJ. Considerações iniciais sobre a dor no câncer e seu controle. Rev Med (São Paulo). 1997;76(1):3-6.;
-
(iv) Dental and periodontal evaluation: DMFT (decayed, missing and filled teeth), plaque and gingival bleeding indexes (PI, BI), probing pocket depth (PPD), cementoenamel junction (CEJ) and clinical attachment level (CAL). The PI evaluated the oral hygiene, which was calculated according to the number of dental surfaces stained by a dental plaque disclosing agent multiplied by 100 and divided by the total number of surfaces, with reference value of ≤30%1414 American Academy of Periodontology. Parameter on chronic periodontitis with slight to moderate loss of periodontal support. J Periodontol. 2000;71(5 Suppl):853-5. http://dx.doi.org/10.1902/jop.2000.71.5-s.853
https://doi.org/10.1902/jop.2000.71.5-s.... . BI evaluated gingival inflammation, and was expressed by the number of bleeding surfaces after probing with a periodontal probe, multiplied by 100 and divided by the total number of surfaces, the reference value of which was ≤20%. The PPD was determined by the distance from the bottom of the pocket to the gingival margin, with reference value of >3 mm. By the periodontal evaluation, gingival hyperplasia or recession was identified. The CAL is calculated by the sum of PPD and CEJ, and its reference value is ≤3 mm (The American Academy of Periodontology, 1999)1414 American Academy of Periodontology. Parameter on chronic periodontitis with slight to moderate loss of periodontal support. J Periodontol. 2000;71(5 Suppl):853-5. http://dx.doi.org/10.1902/jop.2000.71.5-s.853
https://doi.org/10.1902/jop.2000.71.5-s.... ,1515 American Academy of Periodontology. Parameter on chronic periodontitis with advanced loss of periodontal support. J Periodontol. 2000;71(5 Suppl):856-8. http://dx.doi.org/10.1902/jop.2000.71.5-s.856
https://doi.org/10.1902/jop.2000.71.5-s.... ; -
(v) Oral health impact profile (OHIP): validated questionnaire to investigate the impact of oral health on quality of life1616 Barros VM, Seraidarian PI, Cortes MI, Paula LV. The impact of orofacial pain on the quality of life of patients with temporomanibular disorder. J Orofac Pain. 2009;23(1):28-37..
The cognitive evaluation by the neurologist included the Mini Mental State Exam
(cognitive deficit)1010 Brucki SMD, Nitrini R, Carameli P, Bertolucci PHF, Okamoto IH.
Sugestões para o uso do Mini Exame do Estado Mental no Brasil. Arq
Neuropsiquiatr. 2003;61(3B):777-81.
http://dx.doi.org/10.1590/s0004-282x2003000500014
https://doi.org/10.1590/s0004-282x200300...
and the
Questionnaire of Pfeffer for Functional Activity (performed by the caregiver to
determine functionality)1717 Pfeffer RI, Kurosaki TT, Harrah CH, Chance JM, Filos S. Measurement
of functional activities in older adults in the community. J Gerontol.
1982;37(3):323-9. http://dx.doi.org/10.1093/geronj/37.3.323
https://doi.org/10.1093/geronj/37.3.323...
. These
questionnaires are part of the protocol of periodic evaluation of these patients to
investigate respectively the progression of cognitive impairment and its impact on
daily functional activities.
All patients were evaluated at three distinct stages:
1) First evaluation: before the dental treatment;
2) Second evaluation: after one month of the dental treatment;
3) Third evaluation: after 6 months of the second evaluation.
For ethical reasons, in the post-treatment evaluations the patients received further dental treatment if it was necessary.
Dental treatments
The dental diagnoses obtained after the dental evaluation previous to the treatment of the 29 patients are listed in Table 1. Twenty four patients completed the treatment and the first evaluation after the dental treatment (could not come due to sickness not related to AD or severe aggravation of cognitive status due to other reasons not related to the oral condition, and one died). At 6 months, 14 patients were re-evaluated (8 could not come due to sickness not related to AD and 2 died). The treatments performed are shown in Table 2. They were performed by the same dentist, and the most frequent were periodontal treatments (scaling, root planing and periodontal surgery), dental extractions and topic prescription of nystatin. Some of the treatments were made in the same patient or repeated in the post-treatment evaluations.
Statistical analysis
Data were tabled and initially analyzed according to the distribution of quantitative variable by the Shapiro-Wilk test and Q-Q plots. Variables with normal distribution were analyzed by the analysis of repetitive measurements. The non parametric test for the rest of the variables was the MacNemar test. Correlation among the variables with normal distribution was tested with Pearson's for the variables with normal distribution. The level of significance was 5%.
RESULTS
After the initial dental treatment, frequency of pain and its intensity reduced [p=0.014 and p=0.040 respectively, (Table 3)]. There were no differences among the evaluations in bruxism, uncomfortable bite, tinnitus, generalized pain, headache or side of mastication. There was also a reduction in the chronic pain severity index (p=0.014) and of mandibular functional limitations (p=0.011) (Table 4). The oral health impact profile (OHIP) showed quality of life improvement after the dental treatment (p=0.009). There was a positive correlation between mandibular functional limitations, depression and anxiety indexes (p<0.001), which means that higher depression and anxiety indexes were correlated to more mandibular limitations (Table 4). Improvement was also detected in relation to the plaque index (p<0.001), BI (p<0.001) and PPD (p=0.024) (Table 5). Positive correlations were found between DMFT and PI (p<0.001), plaque index and maximum CAL (p=0.004), medium PPD and medium CAL (p<0.001), medium PPD and maximum CAL (p<0.001) and medium CAL and maximum PPD (p<0.001), which means that higher PI was associated with higher DMFT, CAL and PPD.
A significant reduction in the cognitive functional parameters by Pfeffer's questionnaire occurred after the dental treatment (Table 6). There was no correlation between these cognitive and functional indexes with any specific type of dental treatment or with an specific odontologic variable in this study.
DISCUSSION
AD is a progressive and disabling disease that has profound consequences for the
lives of individuals. The aging of the global population is a factor that plays a
role in the increase in the incidence and prevalence of dementia, and supports the
need of functional improvement in the current quality of life of the patients44 Almeida OP, Nitrini R. Demência. São Paulo: Fundo
editorial BYK; 1995.. The health professionals involved
in the assessment of them are looking for strategies beyond the treatment of AD for
secondary morbidities to improve daily life activities, and in this context the oral
health of these patients is one big issue. They have severe oral infections that
cause several types of impairment66 Friedlander AH, Norman DC, Mahler ME, Norman KM, Yagiela JA.
Alzheimer's disease: psychopathology, medical management and dental
implications. J Am Dent Assoc. 2006;137(9):1240-51.
http://dx.doi.org/10.14219/jada.archive.2006.0381
https://doi.org/10.14219/jada.archive.20...
,1818 Avlund K, Holm-Pedersen P, Morse DE, Viitanen M, Winblad B. Tooth
loss and caries prevalence in very old Swedish people: the relationship to
cognitive function and functional ability. Gerodontology. 2004;21(1):17-26.
http://dx.doi.org/10.1046/j.1741-2358.2003.00003.x
https://doi.org/10.1046/j.1741-2358.2003...
,1919 Henriksen BM, Engedal K, Axéll T. Cognitive impairment is
associated with poor oral health in individuals in long-term care. Oral Health
Prev Dent. 2005;3(4):203-7.
http://dx.doi.org/10.3290/j.ohpd.a10824
https://doi.org/10.3290/j.ohpd.a10824...
,2020 Syrjälä AM, Ylöstalo P, Sulkava R, Knuuttila M.
Relationship between cognitive impairment and oral health: results of the Health
2000 Health Examination Survey in Finland. Acta Odontol Scand. 2007;65(2):103-8.
http://dx.doi.org/10.1080/00016350601083521
https://doi.org/10.1080/0001635060108352...
. Recently, evidence has shown a new path for researches,
relating periodontal infections to the perpetuation and aggravation of symptoms of
AD88 Kamer AR. Systemic inflammation and disease progression in Alzheimer
dsease. Neurology. 2010;74(14):1157-8.
http://dx.doi.org/10.1212/WNL.0b013e3181d5df7f
https://doi.org/10.1212/WNL.0b013e3181d5...
,2121 Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, Leon
MJ. Inflammation and Alzheimer’s disease: possible role of periodontal
diseases. Alzheimers Dement. 2008;4(4):242-50.
http://dx.doi.org/10.1016/j.jalz.2007.08.004
https://doi.org/10.1016/j.jalz.2007.08.0...
,2222 Rethman MP. Inflammation in chronic periodontitis and significant
systemic diseases. J Calif Dent Assoc. 2010;38(4):247-57.. Besides, dental infections are potential causes
of orofacial pain as well as masticatory dysfunctions such as TMD, with are also
important co-morbidities2323 Fabri GMC, Siqueira SRDT, Simione C, Nasri C, Teixeira MJ, Siqueira
JTT. Refractory craniofacial pain: is there a role of periodontal disease as a
comorbidity? Arq Neuro-psiquiatr. 2009;67(2B):474-9.
http://dx.doi.org/10.1590/s0004-282x2009000300018
https://doi.org/10.1590/s0004-282x200900...
,2424 Siqueira SRDT, Rolim TS, Teixeira MJ, Nitrini R, Anghinah R,
Siqueira JTT. Oral infections and orafacial pain in Alzheimer’s disease:
case report and review. Dement Neuropsychol. 2010;4(2):145-50..
In this study, after the dental treatment, there was a clear evidence of pain relief (less orofacial complaints, myofascial pain, PI and periodontal infections). These were associated with the decrease in depression and anxiety indexes and better functional aspects by the Pfeffer's questionnaire (p<0.001), which can be correlated or not. As expected, the variables of periodontal disease were correlated between each other (CAL, PPD, BI, PI), and at the 1 month re-evaluation after the initial treatment several procedures were necessary in order to improve the oral health of the patients with limitations in their daily tasks, including oral hygiene. This was reflected in the increase of PI after 6 months, which shows the need of repetitive educational measures and treatments to keep the mouth free from recurrent infections in patients with a progressive disease such as AD.
It is possible that the pain observed at the initial evaluation was associated with
the oral diseases that were treated due to the significant improvement in pain
indexes within the follow-up period (p=0.014). Even the myofascial pain exhibited at
the initial evaluation disappeared, and thus it was probably a consequence of the
oral infections2525 Saczynski JS, Beiser A, Seshadri S, Auerbach S, Wolf PA, Au R.
Depressive symptoms and risk of dementia: The Framingham Heart Study. Neurology.
2010;75(1):35-41.
http://dx.doi.org/10.1212/wnl.0b013e3181e62138
https://doi.org/10.1212/wnl.0b013e3181e6...
,2626 Camparis CM, Siqueira JTT. Sleep bruxism: clinical aspects and
characteristics in patients with and without chronic orofacial pain. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod. 2006;101(2):188-93.
http://dx.doi.org/10.1016/j.tripleo.2005.01.014
https://doi.org/10.1016/j.tripleo.2005.0...
. These conditions cause high
psychosocial impact which can be aggravated2525 Saczynski JS, Beiser A, Seshadri S, Auerbach S, Wolf PA, Au R.
Depressive symptoms and risk of dementia: The Framingham Heart Study. Neurology.
2010;75(1):35-41.
http://dx.doi.org/10.1212/wnl.0b013e3181e62138
https://doi.org/10.1212/wnl.0b013e3181e6...
,2727 Siqueira SRDT, Teixeira MJ, Siqueira JTT. Severe psychosocial
compromise in idiopathic trigeminal neuralgia: case report. Pain Med.
2010;11(3):453-5.
http://dx.doi.org/10.1111/j.1526-4637.2010.00813.x
https://doi.org/10.1111/j.1526-4637.2010...
,2828 Siqueira SR, Nóbrega JC, Teixeira MJ, Siqueira JT. Masticatory
problems after balloon compression for trigeminal neuralgia: a longitudinal
study. J Oral Rehabil. 2007;34(2):88-96.
http://dx.doi.org/10.1111/j.1365-2842.2006.01680.x
https://doi.org/10.1111/j.1365-2842.2006...
,2929 Rolim TS, Fabri GMC, Nitrini R, Anghinah R, Teixeira MJ, Siqueira
JTT et al. Oral infections and orofacial pain in Alzheimer's disease: a
case-control study. J Alzheimers Dis. 2014;38(4):823-9.
http://dx.doi.org/10.3233/JAD-131283
https://doi.org/10.3233/JAD-131283...
. The DMFT index was statistically different after the
dental treatment (p<0.001), which may be associated with the extractions that
were necessary for some patients. Other signs and symptoms that can be associated
with TMD did not differ along the evaluations (bruxism, tinnitus, maximum mouth
opening, side of mastication, headache, generalized pain)2727 Siqueira SRDT, Teixeira MJ, Siqueira JTT. Severe psychosocial
compromise in idiopathic trigeminal neuralgia: case report. Pain Med.
2010;11(3):453-5.
http://dx.doi.org/10.1111/j.1526-4637.2010.00813.x
https://doi.org/10.1111/j.1526-4637.2010...
,2828 Siqueira SR, Nóbrega JC, Teixeira MJ, Siqueira JT. Masticatory
problems after balloon compression for trigeminal neuralgia: a longitudinal
study. J Oral Rehabil. 2007;34(2):88-96.
http://dx.doi.org/10.1111/j.1365-2842.2006.01680.x
https://doi.org/10.1111/j.1365-2842.2006...
,2929 Rolim TS, Fabri GMC, Nitrini R, Anghinah R, Teixeira MJ, Siqueira
JTT et al. Oral infections and orofacial pain in Alzheimer's disease: a
case-control study. J Alzheimers Dis. 2014;38(4):823-9.
http://dx.doi.org/10.3233/JAD-131283
https://doi.org/10.3233/JAD-131283...
,3030 Cicciù M, Matacena G, Signorino F, Brugaletta A, Cicciù A,
Bramanti E. Relationship between oral health and its impact on the quality life
of Alzheimer's disease patients: a supportive care trial. Int J Clin Exp
Med. 2013;6(9):766-72..
One important limitation of this study is the high loss of patients that we had for
the post-treatment evaluations, which may have affected the results and thus this
study should be considered preliminary. AD is a severe and progressive disease and
it is difficult to follow these patients for a long time. However, to our knowledge,
this was the first time that the effect of the dental treatment on emotional,
functional and cognitive aspects was investigated. As a preliminary study, the
sample size was not enough for multivariate analysis. These results are promising
and indicate that the detailed relation between dental treatments and AD progression
needs to be investigated in the future. There was a slight reduction in the
cognitive score by MMSE, which was possibly associated with the progression of the
disease in this 6-month period. It is not possible to know, based on this
preliminary study, whether this index would have undergone more changes in case the
patients were not treated, but some authors have discussed that periodontal
infections may play a role in the cognitive impairment of these patients2222 Rethman MP. Inflammation in chronic periodontitis and significant
systemic diseases. J Calif Dent Assoc. 2010;38(4):247-57.,2828 Siqueira SR, Nóbrega JC, Teixeira MJ, Siqueira JT. Masticatory
problems after balloon compression for trigeminal neuralgia: a longitudinal
study. J Oral Rehabil. 2007;34(2):88-96.
http://dx.doi.org/10.1111/j.1365-2842.2006.01680.x
https://doi.org/10.1111/j.1365-2842.2006...
.
In conclusion, after the dental treatment, a reduction of orofacial pain as well as the improvement of the mandibular function and in the periodontal indexes were detected in the patients with AD, conditions that were maintained until the last evaluation (after 6 months). The recovery of these patients’ oral health had a good impact on their quality of life and functional parameters.
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-
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-
2David R, Piano J, Robert P. Treatment of behavioral disorders in Alzheimer's diseases. Rev Prat. 2011;61(7):939-44.
-
3Scheltens PH, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P et al. Atropht of medial temporal lobes on MRI in “probable” Alzheimer’s disease an normal aging: diagnostics value and neuropsychological correlates. J Neurol Neurosurg Psychiat. 1992;55(10):967-72. http://dx.doi.org/10.1136/jnnp.55.10.967
» https://doi.org/10.1136/jnnp.55.10.967 -
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» https://doi.org/10.1006/brbi.2001.0647 -
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» https://doi.org/10.14219/jada.archive.2006.0381 -
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» https://doi.org/10.1016/0030-4220(81)90072-4 -
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» https://doi.org/10.1212/wnl.34.7.939 -
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Support: This manuscript was supported by FAPESP (Foundation of Research of the State of Sao Paulo, Brazil) – 2007/04930-1 and 2008/05078-0.
Publication Dates
-
Publication in this collection
Dec 2014
History
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Received
05 Nov 2013 -
Reviewed
01 Aug 2014 -
Accepted
21 Aug 2014