Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study.

Bipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.

Art therapy as an adjuvant treatment for depression in elderly women: a randomized controlled trial

Objective: There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. Methods: A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD) stable on pharmacotherapy. The experimental group (EG) was assigned to 20 weekly art therapy sessions (90 min/session). The control group (CG) was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and cognitive measures. Results: Logistic regression analysis adjusted for age revealed that women in EG (n=31) had significant improvement in GDS (p = 0.007), BDI (p = 0.025), and BAI (p = 0.032) scores as compared with controls (n=25). No difference was found in the cognitive measures. Conclusion: Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. Clinical trial registration: RBR-2YXY7Z

Art therapy as an adjuvant treatment for depression in elderly women: a randomized controlled trial.

OBJECTIVE: There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. METHODS: A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD) stable on pharmacotherapy. The experimental group (EG) was assigned to 20 weekly art therapy sessions (90 min/session). The control group (CG) was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and cognitive measures. RESULTS: Logistic regression analysis adjusted for age revealed that women in EG (n=31) had significant improvement in GDS (p = 0.007), BDI (p = 0.025), and BAI (p = 0.032) scores as compared with controls (n=25). No difference was found in the cognitive measures. CONCLUSION: Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. CLINICAL TRIAL REGISTRATION: RBR-2YXY7Z.

Caregiver burden in older adults with bipolar disorder: relationship to functionality and neuropsychiatric symptoms.

BACKGROUND: There are few studies addressing caregivers of bipolar disorder (BD) patients, especially patients who are older adults with an increased need for care, often given by a relative. The aim of this study was to describe which factors increase caregiver burden among caregivers of elderly BD outpatients. METHODS: Patients were older than 60 years and met the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for BD. They were evaluated for current mood, cognitive and other neuropsychiatric symptoms, functionality, medical comorbidities, quality of life, years since BD diagnosis, and number of psychiatric admissions. The caregiver who spent the greatest time with each patient was evaluated with the Zarit Caregiver Burden Interview. The caregivers' global health, mood symptoms, quality of life, and tasks performed for the patient were also assessed. RESULTS: Thirty-six BD patients and their caregivers were assessed. The Zarit Caregiver Burden Interview was positively correlated with patients' neuropsychiatric symptoms (r = 0.508, P = 0.002) and functional impairment (r = 0.466, P = 0.004). The Zarit Caregiver Burden Interview was also correlated with caregivers' own depression (r = 0.576, P < 0.001), anxiety (r = 0.360, P = 0.031), quality of life (r = -0.406, P = 0.014), medical comorbidities (r = 0.387, P = 0.020), and number of tasks that they completed for the patient (r = 0.480, P = 0.003). CONCLUSIONS: In this group of elderly BD patients, caregiver burden was more associated with symptoms frequently seen in others diseases as in dementia than with depressive, manic, or anxiety symptoms, which are often used as treatment outcomes measures goals in BD. Potential treatable and modifiable factors associated with caregiver burden could be caregivers' depression, anxiety, and medical comorbidities, as well as support for caregivers in terms of services and social relationships.

Social skills and psychopathic traits in maltreated adolescents.

Child maltreatment has frequently been associated with impaired social skills and antisocial features, but there are still controversies about the effect of each type of maltreatment on social behaviour. The aim of this study was to compare the social functioning and psychopathic traits of maltreated adolescents (MTA) with a control group (CG) and to investigate what types of maltreatments and social skills were associated with psychopathic traits in both groups. The types and intensity of maltreatment were evaluated through the Childhood Trauma Questionnaire (CTQ) in 107 adolescents, divided into the MTA group (n = 66) and non-maltreated youths (n = 41), our CG. The Hare Psychopathy Checklist: Youth Version (PCL: YV) and a detailed inventory for evaluation of social skills in adolescents were also applied in all individuals. MTA presented more psychopathic traits than the CG, in all domains measured by PCL: YV, independently of IQ levels and the presence of psychiatric disorders. Interestingly, the groups did not differ significantly from each other on indicators of social skills. Multiple regression analysis revealed that emotional neglect was the only maltreatment subtype significantly associated with psychopathic traits, more specifically with the PCL: YV interpersonal factor (F1), and that some social skills (empathy, self-control and social confidence) were related to specific psychopathic factors. The results highlight that emotional neglect may be more detrimental to social behaviours than physical and sexual abuse, and that neglected children require more specific and careful attention.

Cognitive impairment in euthymic older adults with bipolar disorder: a controlled study using cognitive screening tests.

BACKGROUND/OBJECTIVE: Cognitive impairment is a common feature of bipolar disorder (BD), with increased risk of developing dementia in late life. The aim of this study was to investigate the performance on cognitive screening tests in a sample of older adults with BD, as compared to non-BD subjects. METHODS: 186 older adults (86 with BD and 100 without BD) were included. Patients were stratified according to cognitive performance (normal cognition, mild impairment, and dementia). The comparison group comprised healthy controls; subjects with cognitive impairment but no dementia (CIND); or patients with probable or possible Alzheimer disease (AD). Sixty-five subjects were cognitively unimpaired (35 BD), 65 had CIND (25 BD), and 56 AD (26 BD). In each of these levels of cognitive function, we compared the performance of BD and non-BD subjects on the Mini-Mental State Examination (MMSE), verbal fluency test (VFT), and the Clock Drawing Test (CDT). RESULTS: Non-demented patients with BD had a slightly worse global cognitive performance as compared with healthy controls and patients with CIND, as shown by lower scores on the MMSE. Similarly, BD patients performed worse on the VFT, both in the normal cognition range and in the dementia range. Finally, demented BD patients had a significantly worse performance on the CDT as compared with patients with dementia due to AD. CONCLUSION: Older adults with BD perform significantly worse on some cognitive screening tests as compared with those without BD across different levels of cognition.

Cognitive impairment and dementia in late-life bipolar disorder.

PURPOSE OF REVIEW: This work aims to review the most recent publications on cognitive impairment and dementia associated with bipolar disorder (BPD), especially in the elderly. RECENT FINDINGS: In the last years, a growing number of studies aiming at better understanding of cognitive impairment in BPD were found. Impairments found in BPD were compared with other psychiatric disorders and primary cognitive diseases. The impact of cognitive impairment on functionality was also recently highlighted. With respect to neurobiology, studies that explored inflammatory, neurotrophic and pathological cascades possibly associated with BPD and cognition were published. Finally, the first study covering treatment of cognitive impairment was carried out with pramipexole, and it raised important methodological issues for future research in BPD. SUMMARY: Cognitive impairment and dementia in BPD should be better explored with cognitive and functionality protocols along with biological and neuroimaging markers.

Current pharmacological approaches and perspectives in the treatment of geriatric mood disorders.

PURPOSE OF REVIEW: This work aims to review the most recent developments in the treatment of mood disorders (major depression and bipolar disorder) in the elderly. RECENT FINDINGS: In the last years, few new pharmacological interventions for mood disorders have been developed. Recent studies seek to provide alternative treatment strategies to achieve higher remission rates, including the association of antidepressants, mood stabilizers and psychotherapy and the treatment of specific clusters of symptoms, such as the adjunctive treatment of cognitive impairment with cholinesterase inhibitors. Also, recent studies have been assessing the potential of pharmacogenetic information in the prediction of treatment outcomes. SUMMARY: These factors altogether are expected to help the development of personalized treatment strategies that may improve outcomes with fewer adverse effects.

Effects of a multidisciplinary cognitive rehabilitation program for patients with mild Alzheimer's disease.

OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatry symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment.

Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease

OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatry symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment.

Combining cognitive screening tests for the evaluation of mild cognitive impairment in the elderly.

OBJECTIVE: To determine the accuracy of the Mini-Mental State Examination combined with the Verbal Fluency Test and Clock Drawing Test for the identification of patients with mild cognitive impairment and Alzheimer's disease (AD). METHOD: These tests were used to evaluate cognitive function in 247 older adults. Subjects were divided into three groups according to their cognitive state: mild cognitive impairment (n=83), AD (n=81), cognitively unimpaired controls (n=83), based on clinical and neuropsychological data. The diagnostic accuracy of each test for discriminating between these diagnostic groups (mild cognitive impairment or AD vs. controls) was examined with the aid of Receiver Operating Characteristic (ROC) curves. Additionally, we evaluated the benefit of the combination of tests on diagnostic accuracy. RESULTS: Although they were accurate enough for the identification of Alzheimer's disease, neither test alone proved adequate for the correct separation of patients with mild cognitive impairment from healthy subjects. Combining these tests did not improve diagnostic accuracy, as compared to the Mini-Mental State Examination alone, in the identification of patients with mild cognitive impairment or Alzheimer's disease. CONCLUSIONS: The present data do not warrant the combined use of the Mini-Mental State Examination, the Verbal Fluency Test and the Clock Drawing Test as a sufficient diagnostic schedule in screening for mild cognitive impairment. The present data do not support the notion that the combination of test scores is better that the use of Mini-Mental State Examination scores alone in the screening for Alzheimer's disease.

Quality of life and Alzheimers disease: influence of participation at a rehabilitation center / Qualidade de vida e doença de Alzheimer: a influência da participação em um centro de reabilitação

Abstract: Quality of life is seldom explored in evaluations of therapeutic interventions in Alzheimer's disease. Objective: To verify whether participation in a cognitive and functional rehabilitation program improves quality of life (QOL) among Alzheimer's disease (AD) patients. Methods: 19 AD patients participated in this study, 12 of whom attended 24 multi-professional intervention sessions - the experimental group - whereas the remaining 7 comprised the control group. The following tools were used to assess changes: a) Mini-Mental State Examination (MMSE); b) Geriatric Depression Scale (GDS); c) Quality of Life in AD evaluation scale (QOL-AD); d) Open question on QOL. Results: Participation had no positive impact on quantitative clinical variables (MMSE, GDS, QOL-AD). The answers to the open question, examined using the Collective Subject Discourse (CSD) method, suggested that QOL improved after the intervention. Conclusion: Combining pharmacological treatment with psychosocial intervention may prove to be an effective strategy to enhance the QOL of AD patients.

Resumo: Qualidade de vida não é frequentemente explorada na avaliação dos resultados de intervenções terapêuticas em DA. Objetivo: Verificar se a participação em um programa de reabilitação cognitiva e funcional melhora a qualidade de vida (QV) de pacientes com doença de Alzheimer. Metodos: 19 pacientes com DA participaram deste estudo, 12 participaram de 24 sessões de intervenção multiprofissional - grupo experimental - enquanto os 7 restantes compuseram o grupo controle. Os seguintes instrumentos foram utilizados para avaliar mudanças: a) Mini-Exame do Estado Mental (MEEM); b) Escala de Depressão Geriátrica (EDG); c) Escala de Avaliação de Qualidade de Vida na Doença de Alzheimer (QdV-DA); d) questão aberta sobre QV. Resultados: A participação não mostrou efeitos positivos em variáveis clínicas quantitativas (MEEM, EDG, QdV-DA). Os relatos na questão aberta, analisados através da metodologia do discurso do sujeito coletivo (DSC), sugeriram que a QV melhora após a intervenção. Conclusão: Aliar o tratamento medicamentoso às intervenções psicossociais pode ser uma boa estratégia para a melhora da QV dos portadores de DA.

Neuropsychological profile of Brazilian older adults with heterogeneous educational backgrounds.

Education significantly impacts cognitive performance of older adults even in the absence of dementia. Some cognitive tests seem less vulnerable to the influence of education and thus may be more suitable for cognitive assessment of older adults with heterogeneous backgrounds. The objective of this study was to investigate which tests in a cognitive battery were less influenced by educational levels in a sample of cognitively unimpaired older Brazilians. In addition, we evaluated the impact of very high educational levels on cognitive performance. The cognitive battery consisted of the Mini Mental State Examination (MMSE), Cambridge Cognitive Test (CAMCOG), Clock Drawing Test, Short Cognitive Performance Test (SKT), Rivermead Behavioural Memory Test (RBMT), Fuld Object Memory Evaluation (FOME), Verbal Fluency Test (VF) fruit category, Trail Making Test A and B, WAIS-R Vocabulary, and Block Design. Education did not exert a significant influence on the RBMT, FOME, and VF (p < .05). Subjects with very high educational levels had similar performance on the latter tests when compared with those with intermediate and low levels of education. In conclusion, the RBMT, FOME, and VF fruit category seem to be appropriate tools for the assessment of cognitive function in elderly Brazilians with varying degrees of educational attainment.

Quality of life and Alzheimer's disease: Influence of participation in a rehabilitation center.

Quality of life is seldom explored in evaluations of therapeutic interventions in Alzheimer's disease. OBJECTIVE: To verify whether participation in a cognitive and functional rehabilitation program improves quality of life (QOL) among Alzheimer's disease (AD) patients. METHODS: 19 AD patients participated in this study, 12 of whom attended 24 multi-professional intervention sessions - the experimental group - whereas the remaining 7 comprised the control group. The following tools were used to assess changes: a) Mini-Mental State Examination (MMSE); b) Geriatric Depression Scale (GDS); c) Quality of Life in AD evaluation scale (QOL-AD); d) Open question on QOL. RESULTS: Participation had no positive impact on quantitative clinical variables (MMSE, GDS, QOL-AD). The answers to the open question, examined using the Collective Subject Discourse (CSD) method, suggested that QOL improved after the intervention. CONCLUSION: Combining pharmacological treatment with psychosocial intervention may prove to be an effective strategy to enhance the QOL of AD patients.

Qualidade de vida não é frequentemente explorada na avaliação dos resultados de intervenções terapêuticas em DA. OBJETIVO: Verificar se a participação em um programa de reabilitação cognitiva e funcional melhora a qualidade de vida (QV) de pacientes com doença de Alzheimer. METODOS: 19 pacientes com DA participaram deste estudo, 12 participaram de 24 sessões de intervenção multiprofissional ­ grupo experimental ­ enquanto os 7 restantes compuseram o grupo controle. Os seguintes instrumentos foram utilizados para avaliar mudanças: a) Mini-Exame do Estado Mental (MEEM); b) Escala de Depressão Geriátrica (EDG); c) Escala de Avaliação de Qualidade de Vida na Doença de Alzheimer (QdV-DA); d) questão aberta sobre QV. RESULTADOS: A participação não mostrou efeitos positivos em variáveis clínicas quantitativas (MEEM, EDG, QdV-DA). Os relatos na questão aberta, analisados através da metodologia do discurso do sujeito coletivo (DSC), sugeriram que a QV melhora após a intervenção. CONCLUSÃO: Aliar o tratamento medicamentoso às intervenções psicossociais pode ser uma boa estratégia para a melhora da QV dos portadores de DA.

Combining cognitive screening tests for the evaluation of mild cognitive impairment in the elderly

OBJECTIVE: To determine the accuracy of the Mini-Mental State Examination combined with the Verbal Fluency Test and Clock Drawing Test for the identification of patients with mild cognitive impairment and Alzheimer's disease (AD). METHOD: These tests were used to evaluate cognitive function in 247 older adults. Subjects were divided into three groups according to their cognitive state: mild cognitive impairment (n=83), AD (n=81), cognitively unimpaired controls (n=83), based on clinical and neuropsychological data. The diagnostic accuracy of each test for discriminating between these diagnostic groups (mild cognitive impairment or AD vs. controls) was examined with the aid of Receiver Operating Characteristic (ROC) curves. Additionally, we evaluated the benefit of the combination of tests on diagnostic accuracy. RESULTS: Although they were accurate enough for the identification of Alzheimer's disease, neither test alone proved adequate for the correct separation of patients with mild cognitive impairment from healthy subjects. Combining these tests did not improve diagnostic accuracy, as compared to the Mini-Mental State Examination alone, in the identification of patients with mild cognitive impairment or Alzheimer's disease. CONCLUSIONS: The present data do not warrant the combined use of the Mini-Mental State Examination, the Verbal Fluency Test and the Clock Drawing Test as a sufficient diagnostic schedule in screening for mild cognitive impairment. The present data do not support the notion that the combination of test scores is better that the use of Mini-Mental State Examination scores alone in the screening for Alzheimer's disease.

CAMcog as a screening tool for diagnosis of mild cognitive impairment and dementia in a Brazilian clinical sample of moderate to high education.

BACKGROUND: The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut-off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut-off values are also necessary, taking into account cultural and educational effects. METHODS: One hundred and fifty-seven older adults (mean age: 69.6 +/- 7.4 years) with 8 or more years of formal education (mean years of schooling 14.2 +/- 3.8) attending a memory clinic at the Institute of Psychiatry University of Sao Paulo were included. Subjects were divided into three groups according to their cognitive status, established through clinical and neuropsychological assessment: normal controls, n = 62; MCI, n = 65; and mild or moderate dementia, n = 30. ROC curve analyses were performed for dementia vs controls, MCI vs controls and MCI vs dementia. RESULTS: The cut-off values were: 92/93 for dementia vs controls (AUC = 0.99: sensitivity: 100%, specificity: 95%); 95/96 for MCI vs controls (AUC = 0.83, sensitivity: 64%, specificity: 88%), and 85/86 for MCI vs dementia (AUC = 0.91, sensitivity: 81%, specificity: 88%). The total CAMCOG score was more accurate than its subtests Mini-mental State Examination, Verbal Fluency Test and Clock Drawing Test when used separately. CONCLUSIONS: The CAMCOG discriminated controls and MCI from demented patients, but was less accurate to discriminate MCI from controls. The best cut-off value to differentiate controls and demented was higher than suggested in the original publication, probably because only cases of mild to moderate dementia were included. This is important given the need for a diagnostic at earlier stages of Alzheimer's disease.

Mini-mental State Examination performance in mild cognitive impairment subtypes.

BACKGROUND: Diagnosis of mild cognitive impairment (MCI) and its subtypes requires a detailed diagnostic assessment and so may be missed at routine primary-care appointments, since the ordinary dementia screening tests lack sensitivity owing to ceiling effects, especially in highly educated subjects. METHODS: The study was undertaken using a cross-sectional assessment of 112 elderly subjects (mean age 67.96+/-5.77 years, and mean education level of 12.8+/-5.7 years) with a semi-structured interview and a neuropsychological battery. RESULTS: MCI patients did not differ from controls on total MMSE scores (p=0.212). Nevertheless, MCI patients showed worse performance than controls on the verbal memory task (p=0.012), and "drawing a pentagon" (p=0.03). Amnestic MCI patients performed worse only on the "three-word recall" task (p=0.013); non-amnestic MCI patients performed worse on the "three-stage command" task (p=0.001); and multiple-domain MCI patients performed worse on the "drawing a pentagon" task (p=0.001) and had a trend toward performing poorly on the 'three word recall' task (p=0.06). CONCLUSION: The analysis of MMSE subtest scores, in addition to MMSE total scores, may increase the sensitivity of the MMSE test in screening for MCI and its subtypes.

Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder.

Bipolar disorder is associated with increased risk for dementia. We compared the prevalence of Alzheimer's disease between 66 elderly euthymic patients with bipolar disorder who were on chronic lithium therapy and 48 similar patients without recent lithium therapy. The prevalence of dementia in the whole sample was 19% v. 7% in an age-comparable population. Alzheimer's disease was diagnosed in 3 patients (5%) on lithium and in 16 patients (33%) who were not on lithium (P<0.001). Our case-control data suggest that lithium treatment reduced the prevalence of Alzheimer's disease in patients with bipolar disorder to levels in the general elderly population. This is in accordance with reports that lithium inhibits crucial processes in the pathogenesis of Alzheimer's disease.