Rodolfo Braga Ladeira

Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: a preliminary 4-week study.

Several studies have suggested an important role for brain-derived neurotrophic factor (BDNF) in the pathophysiology and therapeutics of bipolar disorder (BPD). The mechanisms underlying the therapeutic effects of lithium in BPD seem to involve a direct regulation of neurotrophic cascades. However, no clinical study evaluated the specific effects of lithium on BDNF levels in subjects with BPD. This study aims to investigate the effects of lithium monotherapy on BDNF levels in acute mania. Ten subjects with bipolar I disorder in a manic episode were evaluated at baseline and after 28 days of lithium therapy. Changes in plasma BDNF levels and Young Mania Rating Scale (YMRS) scores were analyzed. A significant increase in plasma BDNF levels was observed after 28 days of therapy with lithium monotherapy (510.9±127.1pg/mL) compared to pre-treatment (406.3±69.5pg/mL) (p=0.03). Although it was not found a significant association between BDNF levels and clinical improvement (YMRS), 87% of responders presented an increase in BDNF levels after treatment with lithium. These preliminary data showed lithiums direct effects on BDNF levels in bipolar mania, suggesting that short-term lithium treatment may activate neurotrophic cascades. Further studies with larger samples and longer period may confirm whether this biological effect is involved in the therapeutic efficacy of lithium in BPD.

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.

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–linguistic deficits in euthymic elderly patients with bipolar disorder

BACKGROUND There is increasing evidence that bipolar disorder is also associated with neuropsychological impairments persisting during euthymia, thus representing a trait-like feature of the disease. Language and speech abnormalities are also present in bipolar disorder, especially in verbal fluency and verbal memory. However, there is a lack of studies in the literature investigating different levels of linguistic processing (phonological, syntactical, and semantic) in a single cohort of euthymic bipolar patients. Based on previous findings of pervasive language impairment in euthymic elderly bipolar patients, the aim of this study was to comprise a more thorough investigation on the subject. METHODS We studied 19 euthymic bipolar patients aged 60 and above, and 20 cognitively healthy subjects using the Arizona Battery for Communication Disorders of Dementia (ABCD) and the Test for Reception of Grammar Version 2 (TROG-2) in order to assess the phonological, syntactic, and semantic domains of language. RESULTS Bipolar patients performed poorer than controls in Linguistic Expression (p=0.011), in Linguistic Comprehension (Following Commands; p=0.025 and Reading Comprehension of Sentences; p=0.007), and in the TROG-2 (p=0.006). LIMITATIONS The small sample comprising only elderly patients; the lack of statistical power to analyze the potential effect of individual medications on the cognitive performance. CONCLUSIONS Our data demonstrate that linguistic impairment is present in euthymic bipolar patients, affecting mostly syntactic and lexical-semantic abilities, both in comprehension and production of language. These deficits are interrelated with other cognitive skills also known to be affected in bipolar disorder, such as executive functions and episodic memory.

The use of the Clock Drawing Test in bipolar disorder with or without dementia of Alzheimer’s type

There is limited data regarding the cognitive profile from screening tests of older adults with bipolar disorder (BD) with dementia. Objective To investigate the Clock Drawing Test (CDT) among older adults with BD with and without Alzheimers disease (AD). Method 209 older adults (79 with BD without dementia and 70 controls; 60 with AD, being 27 with BD) were included to evaluate the performance of three CDT scoring scales, beyond the Mini-Mental State Examination (MMSE) and verbal fluency (VFT). Results Patients with BD without dementia presented with lower scores in MMSE, VF and one CDT scoring scale than controls. Patients with BD and AD presented with lower scores in VF and CDT scoring scales than patients with only AD. All CDT scales presented similar sensitivity and specificity for BD and non-BD groups. Conclusion Elderly subjects with BD showed greater impairment in CDT in both groups of normal cognition and AD.

Higher proportion of inactive Gsk3β in platelets of elderly patients with bipolar disorder: an effect of treatment?

OBJECTIVE It has been postulated that mood stabilizers inhibit glycogen synthase kinase 3-beta (Gsk3β) activity, mainly through its phosphorylation on serine-9 (Ser9). However, in vivo studies addressing Gsk3β activity in patients with bipolar disorder are scarce. Here, we compare Gsk3β inactivation (as indicated by Ser9-phosphorylation) in platelets of elderly patients with bipolar disorder undergoing clinical treatment and healthy elderly adults not taking medication. METHODS Platelet samples were obtained from 37 elderly adults (bipolar disorder = 19, controls = 18). Relative changes in Gsk3β inactivation was estimated by comparing the ratios of phosphorylated Gsk3β to total Gsk3β (p-Gsk3β Ser9/Gsk3β) between the disease and control groups. RESULTS Phosphorylated-Gsk3β (p < 0.001) and the p-Gsk3β Ser9/Gsk3β ratio (p = 0.006) were elevated in bipolar patients. In the bipolar disorder group, p-Gsk3β Ser9/Gsk3β was positively correlated with serum lithium levels (r = 0.478, p = 0.039). CONCLUSIONS Gsk3β inactivation is higher in this group of elderly adults undergoing treatment for bipolar disorder. However, whether the treatment or the disease causes Gsk3β inactivation was confounded by the lack of an unmedicated, bipolar control group and the non-uniform treatment regimens of the bipolar disorder group. Thus, further studies should help distinguish whether Gsk3β inactivation is an effect of drug treatment or an intrinsic characteristic of bipolar disorder.

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

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.

Caring for an older adult with bipolar disorder is subject to greater burden than caring for dementia

control used more frequently lexis than patients, but also that mild patients used more frequently lexis than moderate, p<0.001. Likewise, it was noted that abstract and living nouns (animals) lexical items were less frequently used by patients, p<.001 and p1⁄40.004 respectively.Conclusions: Comparing the use of lexis between controls and mild and moderate Alzheimer’s disease patients would be interesting to create communication guides that might help caregivers in order to avoid or minimize stressful relationships when dealing with Alzheimer’s disease patients.

Apolipoprotein E polymorphisms do not affect the risk for dementia in elderly patients with bipolar disorder

one that regulates Abmetabolism, is not fully characterized. Here, we studied the regional distribution of apoE and Ab in the brains of cognitively normal individuals.Methods:Gray matter of seven cortical areas (dorsolateral prefrontal, orbitofrontal, inferior temporal, entorhinal, inferior parietal, posterior cingulate and primary visual cortex) and five subcortical areas (thalamus, hypothalamus, striatum, amygdala and cerebellum) were dissected from brains of cognitively normal persons (n 1⁄4 21, average age 1⁄4 91.36 7.1 years, M: F1⁄4 4: 17, average MMSE1⁄4 276 3) and sequentially extracted by 3-step method (TBS, Triton-X and guanidine). The levels of apoE, Ab (1-40) and APP-CTFb (the direct precursor of Ab production) were determined by ELISA. Results: ApoE in TBS and Triton-X fractions were more abundant (over 10-fold) than apoE in guanidine fraction. In TBS and Triton-X fractions, all five subcortical areas had higher apoE level compared to each cortical area (P< 0.05, ANOVAwith Tukey-Kramer test), except for entorhinal cortex, which had higher apoE level, especially in guanidine fraction. Ab level was most abundant in guanidine fraction, followed by Triton-X fraction and TBS fraction. In Triton-X and guanidine fractions, cortical areas had higher Ab level compared to all subcortical areas but amygdala (P< 0.05). There were weak but significant inverse correlations between the regional distribution of apoE in apoE-abundant fractions and Ab (e.g., apoE in TBS fraction vs. Ab in Triton-X fraction; r 1⁄4 -0.385; P< 0.001). APP-CTFb level was lowest in cerebellum among all areas (P< 0.01). Other subcortical areas had similar amount of APPCTFb compared to cortical areas. There were no correlations between the regional distribution of APP-CTFb and apoE or Ab. Conclusions: In the brains of cognitively normal persons, the regional distribution of apoE in apoE-abundant fractions is inversely correlated with the regional distribution of Ab, but not APP-CTFb. These results suggest that apoE likely contributes to regional vulnerability of Ab accumulation by modulating Ab clearance and/or aggregation.

Combined instruments for the diagnosis of mild cognitive impairment in the elderly

of the rate of decline using simple brief cognitive computerized tests could facilitate both detection of healthy individuals with early neurodegenerative disease, and have utility as an outcome measure in trials of putative disease-modifying therapies for AD. The results of this study will help determine the minimum and optimal periods required for trials aiming to modify rate of decline, as well as characterize differences between pre-AD conditions and established AD. Reliable estimates of the rate of change in cognitive function should aid trial design and improve statistical power for future novel study trials.