Karoline Carvalho Carmona

High cortisol levels are associated with cognitive impairment no-dementia (CIND) and dementia

BACKGROUND This study aimed to compare serum cortisol concentrations in cognitively healthy elderly and in subjects with cognitive impairment no dementia (CIND) and dementia, besides to evaluate these concentrations according to apolipoprotein E genotype (APOE). METHODS Three-hundred and nine elderly enrolled in the Pietà Study (Brazil) were divided in 3 groups: control (n=158), CIND (n=92) and dementia (n=59) and had concentrations of morning serum cortisol measured. Hormone concentrations were measured by chemiluminescence and APOE genotypes were determined by PCR followed by restriction fragment length polymorphism (RFLP). RESULTS Medians of cortisol concentrations (μg/dl) for the groups were 12.14 (interquartile range - IQR 6.34) for control, 13.65 (IQR 5.88) for CIND and 14.47 (IQR 7.35) for dementia. Significant differences were observed for control vs. CIND (P=0.003), control vs. dementia (P=0.001), but not for CIND vs. dementia (P=0.269). No association was observed between cortisol concentrations and APOE genotype among the groups (P=0.348). CONCLUSIONS The elevation in cortisol concentrations is associated with dementia, independently of APOE genotypes. Further studies are required to understand if elevation of cortisol is an initial event and how hippocampal damage and the loss of hypothalamus-pituitary-adrenal (HPA) axis inhibition may affect its concentrations.

Cortisol, HDL-c, VLDL-c, and APOE Polymorphisms as Laboratorial Parameters Associated to Cognitive Impairment No Dementia (CIND) and Dementia

Population aging is a global phenomenon whose main consequence is the increase of chronic degenerative diseases, including dementia. The aim of this case–control study was to evaluate the laboratorial parameters lipid profile, cortisol, and apolipoprotein E (APOE) gene genotype, comparing cognitively healthy controls and subjects with cognitive impairment no dementia (CIND) and dementia in a group of elderly people.

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.

Operationalized definition of older adults with high cognitive performance

ABSTRACT Recently, there has been an increasing number of studies on exceptional cognitive aging. Herein, we aim to objectively provide the operationalized characterization of older adults with unusually high memory ability. Some authors have defined them as “SuperAgers”, individuals aged 80 years or older with memory ability similar or superior to middle-aged subjects. On the other hand, the terminology “high-performing older adults” (HPOA) seems to appropriately conceptualize these individuals without exaggeration. A threshold for age is not a reliable criterion, but may be defined as 75 and 80 years of age for developing and developed countries, respectively. We propose that HPOA may exhibit episodic memory test scores equal to or greater than those of individuals aged 50-60 years, according to the validated tables for the respective country. This group must also have global cognition scores within expected average values for age and education. Executive functioning may play a central role in the exceptional memory performance of this group. Further studies are essential to confirm existing findings and may provide important evidence for cognitive aging theory and the neurobiology of dementia.

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

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.

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.

Extrapyramidal features and white matter lesions in healthy aging, cognitive impairment and dementia: The PIETÀ study

economic cost savings. Visual impairments are common in AD (Kirby, 2010) and may affect eye movement patterns during face recognition and other visual tasks. Anecdotal evidence from the clinic often includes an early loss of recognition (faces, routes) in incipient dementia, particularly at dusk when contrasts are low. Many clinicians also report an ‘Alzheimer’ feel upon meeting AD patients. This maybe based on the way that people with AD scan faces. We found that pairing of emotional expressions, but not naming of the emotional expressions was lower in AD cases than controls, indeed suggesting impairments in facial scanning which then limits recognition and matching (Burnham,2003). Methods: We have developed a visual sensitivity test which incorporates detection of randomly placed low and high-contrast stimuli, as well as face and emotional recognition tasks. The advantage of the visual sensitivity test is that it is short (3 min), reliable (little learning effect) and does not provoke test anxiety as many other cognitive tests do (Bandelow,2008). These computer-based tests yield behavioural data based on participant responses, as well as integrated eye tracking data.Results:Our research at theOxfordProject To InvestigateMemory and Ageing showed that patients withMild Cognitive Impairment (MCI, n1⁄4 15) took longer to detect targets than age-matched controls (n 1⁄4 67). Of particular interest was the loss of central visual field detection speed advantage inMCI participants compared to controls. Age-related visual disease (macular degeneration, cataract, glaucoma, diabetic retinopathy) were controlled for in this study. We will also present novel results from eye movement patterns during this test and the face and emotion recognition tests. The eye tracking data is analysed to identify common patterns that differ between theparticipant groups, andwhether thesepatternshave sufficient discriminatory capacity to accurately diagnose MCI and dementia. Conclusions: Our studies suggest that differences in eye scanningpatternsmaybe indicativeof some of thecognitivedeficits seen inAD.This approachcouldbeused tonon-invasively screen for AD.