Elisa de Paula França Resende

Cognitive performance of community-dwelling oldest-old individuals with major depression: the Pietà study

BACKGROUND Individuals with late-life depression (LLD) may present cognitive symptoms. We sought to determine whether a brief cognitive battery (BCB) could identify cognitive and functional deficits in oldest-old individuals with LLD and a low level of education. METHODS We evaluated 639 community-dwelling individuals aged 75+ years in Caeté (MG), Brazil. We used the MINI and GDS-15 to diagnose major depression and evaluate its severity, respectively. The cognitive evaluation comprised the Mini-Mental State Examination (MMSE), BCB, clock-drawing test, category fluency test (animals) and Pfeffers Functional Activities Questionnaire (FAQ). RESULTS Fifty-four (11.6%) of the included individuals were diagnosed with LLD; on average, these participants were aged 81.0 ± 4.8 years and had 3.9 ± 3.4 years of schooling, and 77.8% of the subjects with LLD were female. Depressed individuals scored lower than subjects without dementia/depression on the MMSE overall (p < 0.001) and on several of the MMSE subscales, namely, time (p < 0.001) and spatial orientation (p = 0.021), attention/calculation (p = 0.019), and language (p = 0.004). Individuals with LLD performed worse on the incidental and (p = 0.011) immediate memory (p = 0.046) and learning tasks (p = 0.039) of the BCB. Individuals with LLD also performed worse on the category fluency test (p = 0.006), clock-drawing test (p = 0.011) and FAQ (p < 0.001). Depression severity was negatively correlated with incidental memory (ρ = -0.412; p = 0.003) and positively correlated with FAQ score (ρ = 0.308; p = 0.035). In the multiple regression analysis, only temporal orientation and FAQ score remained independently associated with LLD. CONCLUSION Individuals with depression and a low level of education presented several cognitive and functional deficits. Depression severity was negatively correlated with incidental memory and functionality. Our findings serve as a description of the presence of cognitive dysfunction in individuals with LLD and suggest that these deficits may be identified based on the results of a BCB.

Accuracy of the 15-item Geriatric Depression Scale (GDS-15) in a community-dwelling oldest-old sample: the Pietà Study

INTRODUCTION Late-life depression (LLD) is common, but remains underdiagnosed. Validated screening tools for use with the oldest-old in clinical practice are still lacking, particularly in developing countries. OBJECTIVES To evaluate the accuracy of a screening tool for LLD in a community-dwelling oldest-old sample. METHODS We evaluated 457 community-dwelling elderly subjects, aged ≥75 years and without dementia, with the Geriatric Depression Scale (GDS-15). Depression diagnosis was established according to DSM-IV criteria following a structured psychiatric interview with the Mini International Neuropsychiatric Interview (MINI). RESULTS Fifty-two individuals (11.4%) were diagnosed with major depression. The area under the receiver operating characteristic (ROC) curve was 0.908 (p<0.001). Using a cut-off score of 5/6 (not depressed/depressed), 84 (18.4%) subjects were considered depressed by the GDS-15 (kappa coefficient = 53.8%, p<0.001). The 4/5 cut-off point achieved the best combination of sensitivity (86.5%) and specificity (82.7%) (Youdens index = 0.692), with robust negative (0.9802) and reasonable positive predictive values (0.3819). CONCLUSION GDS-15 showed good accuracy as a screening tool for major depression in this community-based sample of low-educated oldest-old individuals. Our findings support the use of the 4/5 cut-off score, which showed the best diagnostic capacity.

Klüver & Bucy syndrome: an investigation of social and affective cognition

ABSTRACT Klüver-Bucy syndrome (KBS) leads to important behavioral symptoms and social maladaptation. Rarely described, no previous study has investigated its social and affective cognitive profile. We report the case of ASP, a patient who developed a complete KBS at 9 years that evolved into an incomplete KBS. Orbitofrontal and temporal damages were evidenced. While a classic neuropsychological assessment showed a preserved global functioning, an extensive evaluation of her social and affective cognition (reversal learning, decision-making, emotion recognition, theory of mind, creative thinking) showed remarkable deficits. The relevancy of such findings for the characterization KBS and the field of neuropsychology are discussed.

REGIONAL NEUROFIBRILLARY TANGLE DISTRIBUTION AS A CONTRIBUTOR TO CLINICAL HETEROGENEITY IN ALZHEIMER’S DISEASE

year) showed a slower rate of cognitive decline compared to the untreated HpSp (-7.1 points/year) and typical cases (-1.6), although not significant (p1⁄40.141 and p1⁄40.245, respectively). Limbic predominant did not show a difference (p1⁄40.901). Conclusions: The findings support the hypothesis that neuropathologic heterogeneity ofAD subtypes extends to the differential involvement of the cholinergic system. Although caution is needed due to the retrospective nature of our study, our findings suggest that cholinergic treatment may have a greater benefit in HpSp subtype of AD.

PRIMARY SCHOOL EDUCATION CAN BE SUFFICIENT TO MODERATE THE RELATIONSHIP BETWEEN HIPPOCAMPUS VOLUME AND MEMORY PERFORMANCE

F3-04-02 PRIMARY SCHOOL EDUCATION CAN BE SUFFICIENT TO MODERATE THE RELATIONSHIP BETWEEN HIPPOCAMPUS VOLUME AND MEMORY PERFORMANCE Elisa de Paula França Resende, Howard J. Rosen, Kevin Chiang, Isabel Allen, Adam M. Staffaroni, Lea Tenenholz Grinberg, Karoline Carvalho Carmona, Henrique Cerqueira Guimaraes, Viviane Amaral Carvalho, Maira Tonidandel Barbosa, Leonardo Cruz de Souza, Paulo Caramelli, University of California, San Francisco, San Francisco, CA, USA; University of California San Francisco, San Francisco, CA, USA; Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Contact e-mail: elisa.resende@gbhi.org

CEREBROSPINAL FLUID LEVELS OF ANGIOTENSIN-CONVERTING ENZYME ARE ASSOCIATED WITH AMYLOID-β IN ALZHEIMER’S DISEASE

have investigated the role of trans-acting factors; transcription factor SOX2 and miRNA-140, in ADAM10 gene regulation. The entire sequence of ADAM10 gene is analyzed by computational bioinformatics and screened for probable trans-actors with high regulatory importance. Results: Our study shows that miRNA-140-5p has enhanced expression in AD post-mortem brain hippocampus using high throughput micro-arrays and qRT-PCR. Interestingly we have also seen that miRNA-140 seed sequence is present on both ADAM10 and SOX2 3’UTR and thus reporter constructs containing regulatory elements were transfected into human cell lines along with miRNA-140 mimics and inhibitors to evaluate their interaction by dual luciferase reporter assays. The specific interaction of miRNA-140 with both ADAM10 and its transcription factor SOX2 signifies high regulatory importance of this miRNA in controlling ADAM10 expression.Conclusions:Thus our proposed investigation unravels the mechanisms underlying ADAM10 downregulation bymiR-140 that exacerbates Alzheimer’s disease related neurotoxic effects. Our findings could reflect a strong basis for future research aimed at understanding the potential contribution of trans-acting factors as a biomarker or modulator of AD pathophysiology.

EDUCATION CAN STRENGTHEN THE ROLE OF THE LEFT HIPPOCAMPUS IN EPISODIC MEMORY PERFORMANCE

disease (AD). Methods:13 controls, 18 MCI and 11 AD subjects underwent T1-MPRAGE and PET imaging with the tau ligand [F]-AV-1451. Atrophy was measured from MRI and the simplified reference tissue model (SRTM) was applied to the [F]-AV-1451 PET data to quantify both tau deposition (binding; BPND) and perfusion (relative to the cerebellum; R1). T1 data were processed with Freesurfer 6 beta to derive cortical thickness maps. PET data were co-registered to the T1 and sampled onto the cortical surface (Greve et al., 2014) (Figure 1). Zscore maps of tau, hypoperfusion and atrophy were derived for each subject with reference against the healthy controls. Surface-based comparisons of tau, perfusion, and atrophy were compared between the groups. Paired T-Tests were used to compare the global Z score of each marker, and correlations across the brain regions were performed to assess the interrelationship among tau, hypoperfusion and cortical thickness. Results:There was a striking overlap of tau deposition, hypoperfusion and cortical thinning in the AD group (Figure 2). Relative to healthy controls, the AD group showed a widespread increase in tau, together with an overlapping but more restricted pattern of hypoperfusion and cortical thinning in temporo-parietal cortices (Figure 3). The three markers of pathology were highly intercorrelated in AD (Figure 4). Tau Z (3.0 61.4) significantly exceeded both atrophy Z (0.8 6 0.7, p < 0.001) and hypoperfusion Z (0.4 6 0.5, p<0.001) (Figure 5). MCI showed increased tau in the left inferior temporal cortex compared to healthy controls. In MCI, tau Z was significantly correlated with atrophy Z (r 1⁄4 0.4, p 1⁄4 0.002), but tau Z was similar compared to atrophy Z. Conclusions:The wider extent and greater severity of tau relative to atrophy and hypoperfusion provide preliminary in vivo evidence to support a model in which tau pathology precedes neurodegeneration in AD. This hierarchy was not observed in the MCI group, and may suggest an acceleration of tau during the progression from MCI to AD.

Mapping the affective syndrome in Alzheimer's disease.

D ementia due to Alzheimers disease (AD) is becoming more frequent with the rapid growing of life expectancy and also with the continuous improvement of the clinical diagnosis 1. Neuropsychiatric symptoms are very common over the course of AD dementia, adding substantial burden for families and caregivers 2. These symptoms are usually fluctuating in intensity and are often difficult to be treated. Apathy is the most common behavioral disorder across all stages of AD 2,3. Depression and anxiety are also very common, especially in mild and moderate stages, frequently worsening cognitive and functional performances 2. The main neuropsychiatric symptoms of de-mentia can be easily assessed by the Neuropsychiatric Inventory (NPI) 4. The neural correlates of these behavioral symptoms have been explored in several structural neuroimaging studies, mainly with magnetic resonance imaging (MRI) using voxel-based morphometry (VBM). In one study 5 conducted with this technique delusions were associated with atrophy in the left frontal lobe, right frontoparietal cortex and left claustrum. Apathy was associated with atrophy in anterior cingulate, medial frontal cortex and putamen bilaterally, and also with the head of left caudate nucleus. Agitation correlated with gray matter loss in left insula and anterior cingulate cortex bilaterally. Another study 6 showed that agitation was related to atrophy in the left inferior and middle frontal/ insula and bilateral retrosplenial cortices. Aberrant motor behavior was related to atrophy in the right basal ganglia and right inferior frontal cortex, and depression, with atrophy in the left middle frontal cortex. Voxel-based cortical thickness (VBCT) also seems to be a good way to assess atrophy, allowing identification of structural changes several years before the emergence of demen-tia 7. In this issue of Arquivos de Neuro-Psiquiatria, Hayata and colleagues 8 used the VBCT technique to contrast AD dementia patients and elderly cognitively healthy controls, and found similar results to those reported with VBM 9. The investigators found widespread cor-tical atrophy in the AD group, involving the left middle and inferior temporal gyri, posterior regions of right superior temporal sulcus, isthmus of the cingulate gyrus, left posterior cin-gulate cortex, and right fusiform gyrus. They also found atrophy in the frontal and parietal lobes, insula, entorhinal cortex, precuneus and anterior cingular cortex, all of them bilaterally. The authors found significant correlations between affective syndrome (depression and anxiety) with reduced cortical thickness in the insula, lateral orbitofrontal and temporal pole, all from the right side. Conversely, they found no …

The structural basis of performance in an episodic memory test in an elderly population with heterogeneous educational level: The pietà study

patients with confirmed diagnosis of AD (11.8% increase V1⁄449, p<.05; Figure 2) and those with confirmed diagnosis of non-AD (13.6% increase; V1⁄40, p<.05; Figure 3). 243 PET scans were evaluated by two nuclear medicine physicians, who disagreed on 32 cases (rate of concordance: 86.8%). Conclusions:Data are in line with previous reports. Based on preliminary results, amyloid PET with 18F-Florbetapir has a significant impact on diagnosis and diagnostic confidence of dementia experts.

Descriptive performance in functional activities questionnaire and mini-mental state examination according to educational level and functional staging assessment (FAST) in a community-based sample of brazilian oldest old: The pietà study

CN vs CDALL SMCQ 34.0 103.297 616.750 1 <0.001 SMCQ vs SMCQ-SIRQD: p<0.001 SIRQD vs SMCQ+SIRQD p1⁄40.009 SIRQD 90.6 153.724 261.848 1 <0.001 SMCQ-SIRQD 92.0 160.632 254.939 0.008 CN vs MCI SMCQ 59.9 15.672 354.374 1 <0.001 SMCQ vs SMCQ+SIRQD: p<0.001 SIRQD vs SMCQ+SIRQD p1⁄40.074 SIRQD 67.5 19.927 197.572 1 <0.001 SMCQ+SIRQD 68.1 23.108 194.385 <0.001 CN vs CDAD SMCQ 78.7 90.226 553.431 1 <0.001 SMCQ vs SMCQ+SIRQD: p<0.001 SIRQD vs SMCQ+SIRQD p1⁄40.005 SIRQD 89.5 139.632 237.998 1 <0.001 SMCQ+SIRQD 90.3 147.539 230.091 <0.001 CN vs aMCI SMCQ 62.9 18.602 328.876 1 <0.001 SMCQ vs SMCQ+SIRQD: p<0.001 SIRQD vs SMCQ+SIRQD p1⁄40.033 SIRQD 70.3 22.03 3 187.385 1 <0.001 <0.001 SMCQ+SIRQD 69.0 26.575 182.843 <0.001 CN vs CDNAD SMCQ 70.7 85.454 348.640 1 <0.001 SMCQ vs SMCQ-SIRQD: p<0.001 SIRQD vs SMCQ+SIRQD p1⁄40.314 SIRQD 88.9 130.104 137.380 1 <0.001 SMCQ+SIRQD 89.4 131.118 136.367 <0.001 CN vs naMCI SMCQ 89.1 0.023 101.139 1 0.878 SMCQ vs SMCQ-SIRQD: p<0.001 SIRQD vs SMCQ+SIRQD p1⁄40.335 SIRQD 88.7 0.285 49.710 1 0.581 SMCQ+SIRQD 88.7 0.213 48.782 2 0.126