FAS Verbal Fluency Research Articles

637-P: Sex-Specific Associations between Fatty Acid–Derived Oxylipins and Executive Function in T2DM

T2DM increases the risk of cognitive decline, especially in women. Sex-specific associations between lipids and cognition have been reported, though underlying mechanisms remain unclear. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been linked to both T2DM and cognitive dysfunction. CYP450s convert long-chain polyunsaturated fatty acids into epoxides which are anti-inflammatory and help resolve inflammation, however sEH metabolizes these into inactive or cytotoxic diols, limiting their benefits. We hypothesized that oxylipin epoxides and diols of arachidonic acid (AA) and docosahexaenoic acid (DHA) would be associated with cognition in people with T2DM, particularly in women. Women and men with T2DM were recruited as part of the study. Twenty-two fasting serum free oxylipins were quantified by ultra-high performance liquid chromatography tandem mass spectrometry. Executive function was assessed using a composite z-score from the following tests: Stroop Colour-Word Interference Victoria Version, FAS Verbal Fluency, Digit Symbol Substitution, and Trails Making Test Part B. All analyses controlled for age, sex, BMI, HbA1c and years of education. Among 72 individuals with T2DM (mean age 61.8±9.2, mean HbA1c 7.4±0.1%, 53% women), demographic characteristics, oxylipin concentrations and cognitive performance did not differ between women and men. Some CYP450-derived epoxides of DHA and AA were associated with lower executive function scores in women, but with higher scores in men. Epoxide × sex interactions were found for 3 of 4 DHA epoxides (16(17) [F=20.2, p<0.001]; 13(14) [F=8.5, p=0.005]; and 10(11) [F=7.4, p=0.009]), and for the 14(15) AA epoxide [F=3.9, p<0.05]). Circulating concentrations of the corresponding diols were not associated with executive function. These associations between epoxides and executive function suggest a sex difference in the relevance of the CYP450 pathway to cognitive performance in T2DM. Disclosure S.Ryoo: None. B.R.Shah: None. J.Gilbert: Speaker's Bureau; Abbott, AstraZeneca, Amgen Canada, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Sanofi, Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Novo Nordisk Canada Inc. A.Assal: None. I.Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd./Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk. A.Taha: None. W.Swardfager: None. N.Z.Anita: None. C.Major-orfao: None. W.Lin: None. S.Noor: None. F.Kwan: None. K.L.Lanctôt: Consultant; Exciva, GW Pharmaceuticals, ICG Farma, Merck Sharp & Dohme Corp., Novo Nordisk, Sumitomo Pharma Co. Ltd., Other Relationship; BioXcel, Cerevel Therapeutics, H Lundbeck A/S. N.Herrmann: None. P.Oh: Advisory Panel; Novartis Canada. Funding Canadian Institutes of Health Research; Banting & Best Diabetes Centre; National Institute of Diabetes and Digestive and Kidney Diseases

A-241 Five Point Test: Reliability, Validity, and Test Performance in Cognitively Intact Adults

Abstract Objective Reliability and validity evidence related to the Five Point Test (FPT) scores is severely limited. The primary purpose of this study was to examine psychometric evidence related to two commonly used FPT scores (number of unique designs (UD), percentage of repetitions (PR)) using one-week test–retest reliability, correlations with demographic and neuropsychological variables, and convergent validity in line with a regression-based explanation-focused view of validity. Methods The sample consisted of 86 cognitively intact, non-depressed adult men and women ages 21–82 years (M = 52.7, SD = 17.7) with 7–21 years of education (M = 14.2, SD = 3.13) recruited from the general community and tested individually. Results UD ranged from 8–60 (M = 35.4) and PR ranged from 0–45% (M = 6.9%). Test–retest coefficients were .83 for UD but only .43 for PR. Age was significantly correlated with UD (r = −.59) and PR (r = .23). Education was significantly correlated with UD (r = .26) but not PR (r = −.10). There were no gender differences. UD showed significant bivariate correlations with WAIS-III Block Design, Trail-Making Test (TMT) A, TMT-B, Bicycle Drawing Test, and FAS Verbal Fluency but, together in a regression, only age and TMT-B remained significant. PR scores did not correlate significantly with any neuropsychological variables. Conclusion UD showed strong test–retest reliability. UD performance tends to be poorer with older age and less education. The meaning and interpretation of UD performance using a regression-based explanation-focused view of validity will be discussed. PR reliability is poor even over a short interval and attenuates subsequent statistical findings. Use of PR is not recommended in research or practice.

Cognitive Decline in Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease: A Prospective Cohort Study

ObjectiveWe explored whether the mild cognitive impairment (MCI) stages of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) differ in their cognitive profiles, and longitudinal progression. DesignA prospective, longitudinal design was utilized with annual follow-up (Max 5 years, Mean 1.9, standard deviation 1.1) after diagnosis. Participants underwent repeated cognitive testing, and review of their clinical diagnosis and symptoms, including evaluation of core features of DLB. SettingThis was an observational study of independently living individuals, recruited from local healthcare trusts in North East England, UK. ParticipantsAn MCI cohort (n = 76) aged ≥60 years was utilized, differentially diagnosed with MCI due to AD (MCI-AD), or possible/probable MCI with Lewy bodies (MCI-LB). MeasurementsA comprehensive clinical and neuropsychological testing battery was administered, including ACE-R, trailmaking tests, FAS verbal fluency, and computerized battery of attention and perception tasks. ResultsProbable MCI-LB presented with less impaired recognition memory than MCI-AD, greater initial impairments in verbal fluency and perception of line orientation, and thereafter demonstrated an expedited decline in visuo-constructional functions in the ACE-R compared to MCI-AD. No clear diagnostic group differences were found in deterioration speeds for global cognition, language, overall memory, attention or other executive functions. ConclusionThese findings provide further evidence for differences in severity and decline of visuospatial dysfunctions in DLB compared with AD; further exploration is required to clarify when and how differences in attention, executive, and memory functions emerge, as well as speed of decline to dementia.

Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind, placebo-controlled trial.

Paroxetine and fluconazole have neuroprotective effects in an in vitro model of HIV protein-mediated neuronal injury. This study evaluated the safety, tolerability, and efficacy of both paroxetine and fluconazole for the treatment of HIV-associated neurocognitive disorder (HAND). A 24-week randomized double-blind, placebo-controlled 2×2 factorial design study was used. HIV+ individuals with cognitive impairment were enrolled in the 24-week trial. Participants were randomly assigned to one of four groups: (1) paroxetine 20mg/day, (2) fluconazole 100mg every 12h, (3) paroxetine and fluconazole, or (4) placebo. Safety, tolerability, and efficacy were evaluated. Forty-five HIV+ individuals were enrolled. Medications were well tolerated. Compared to no paroxetine arms, HIV+ individuals receiving paroxetine showed improved NPZ8 summary scores, (mean change=0.25 vs - 0.19, p=0.049), CalCAP sequential test reaction time (mean change=0.34 vs -0.23, p=0.014), Trail Making Part B test performance (mean change=0.49 vs - 0.33, p=0.041), and FAS verbal fluency (mean change=0.25 vs 0.02, p=0.020) but a decline in the Letter number sequencing test (mean change=- 0.40 vs 0.26, p=0.023). Biomarkers of cellular stress, inflammation, and neuronal damage were not affected by paroxetine. HIV+ individuals receiving fluconazole did not show a benefit in cognition and showed an increase in multiple markers of cellular stress compared to the no fluconazole arms. In conclusion, paroxetine was associated with improvement in a summary neuropsychological test measure and in several neuropsychological tests but worse performance in one neuropsychological test. Further studies of paroxetine for the treatment of HAND and to define its precise neuroprotective properties are warranted.

P306 Motor cortex tRNS reduce pain and improve affective and cognitive impairment in patients with fibromyalgia: Preliminary results of a randomized sham-controlled trial

Background Fibromyalgia (FMS) is a clinical syndrome characterized by widespread musculoskeletal pain, chronic fatigue, cognitive deficit, sleep and mood disorders. Most pharmacological therapies showed limited effectiveness and there’s need for new effective and well tolerated therapeutic tools. Recently, transcranial direct-current stimulation (tDCS) of motor cortex showed able to reduce pain, while dorsolateral prefrontal cortex (DLPFC) tDCS improved anxiety, depression and cognitive impairment in FMS. A new application, random noise stimulation (tRNS), using randomly changing alternating currents, showed very recently ability to ameliorate working memory and pain in limited series of FMS and neuropathic pain patients. Here we explored the clinical effects of primary motor cortex (M1) tRNS in FMS patients. Materials and methods Twenty female patients with FMS between the ages of 26 and 67 were randomized into two treatment groups undergoing daily stimulation sessions for two weeks (weekend free): one received active, real tRNS and the other one sham, placebo tRNS. Each patient was evaluated, before and after treatment, through Visual Analogue Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS) and other specific neurophychological tests, such as Trail Making Test (TMT), Rey Auditory Verbal Learning Test (AVLT), Forward and Backward Digit Span, FAS verbal fluency test. Results M1 active tRNS, compared to sham, induced a general improvement of FMS clinical picture: pain, depression, anxiety and FIQ scores showed significant reduction. Even TMT A, AVLT and FAS scores improved significantly. Discussion and conclusions These findings suggest M1 tRNS can be very effective in relieving symptoms of fibromyalgia. Differently from motor cortex tDCS, tRNS seems able to counteract not only pain but also cognitive disturbance in these patients. This could follow to the invoked mechanism of stochastic resonance that would bring to a synchronization of neural firing and so more spreading and lasting effects.

High Frequency of GBA Gene Mutations in Dementia With Lewy Bodies Among Ashkenazi Jews

Mutations in the glucocerebrosidase (GBA) gene are a risk factor for the development of dementia with Lewy bodies (DLB). These mutations are common among Ashkenazi Jews (AJ) and appear to have an effect on the natural history of the disease. To evaluate the clinical and genetic characteristics of an AJ cohort of patients diagnosed with DLB, assess the association of phenotype of DLB with GBA mutations, and explore the effects of these mutations on the clinical course of the disease. Thirty-five consecutively recruited AJ patients with newly diagnosed clinically probable or possible DLB underwent genotyping for the 7 known AJ GBA mutations and the LRRK2 G2019S mutation. Two patients with the LRRK2 G2019S mutation were excluded from the final analysis. Data were collected from July 1, 2013, to July 31, 2015. Assessment of clinical markers included the following standardized scales: Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT), REM (Rapid Eye Movement) Sleep Behavior Disorder Single-Question Screen, Geriatric Depression Scale, and Montreal Cognitive Assessment. Motor symptoms were assessed with the Unified Parkinson's Disease Rating Scale motor part III. A subset of 15 patients also underwent assessment with the Color Trail Making Test, FAS verbal fluency, Digit Span, Hooper Visual Organization Test, and Stroop test. Among the 35 patients with DLB (23 men [66%] and 12 women [34%]; mean [SD], 69.6 [8.2] years), 11 (31%) were carriers of mutations in the GBA gene. Among the 33 patients undergoing further analysis, the GBA mutation carriers were younger at symptom onset (mean [SD] age, 65.7 [11.7] vs 72.1 [5.1] years; P = .03), had more frequent visual hallucinations that did not achieve significance (9 of 11 [82%] compared with 12 of 22 [55%]; P = .052), and had higher scores on the RBD questionnaire (mean [SD], 7.8 [2.2] vs 5.1 [3.3]; P = .03). After adjusting for age and duration of symptoms, testing revealed that GBA mutation carriers had poorer cognition as assessed by the Montreal Cognitive Assessment Battery (mean [SD] score, 18.75 [5.99] vs 23.23 [3.16]; P = .03), lower scores on tests of verbal fluency (adjusted z scores, 0.50 vs -2.02; P = .02), worse scores on tests of visuospatial function (adjusted t scores, 68.55 vs 79.57; P = .046), and higher mean (SD) scores on the Unified Parkinson's Disease Rating Scale motor part III (36.72 [10.62] vs 25.72 [10.32]; P = .03). One in 3 AJ patients diagnosed with DLB were carriers of a GBA mutation, making it the most common genetic mutation identified in association with this disease and with any dementia disorder. Mutations in the GBA gene were associated with more severe motor and cognitive dysfunction, supporting a specific contribution of the GBA gene or lysosome function to this clinical syndrome.

Social vulnerability and prefrontal cortical function in elderly people: a report from the Canadian Study of Health and Aging

Prefrontal cortical lobe function is related to social behavior in humans. We investigated whether performance on tests of prefrontal cortical function was associated with social vulnerability. Associations with non-frontal cognitive function were investigated for comparison. 1216 participants aged 70+ of the Canadian Study of Health and Aging-2 screening examination, who also underwent detailed neuropsychological testing, comprised the study sample. Performance on WAIS-R abstraction, WAIS-R comprehension, Trails B, FAS and category verbal fluency, Block construction, Token Test and Wechsler Memory Scale Information Subset was tested in relation to the participant's level of social vulnerability using regression models adjusted for age, education, sex, frailty, MMSE score, diagnosis of depression, and use of psychoactive medications. Social vulnerability was measured by an index comprising many social problems or "deficits". The most socially vulnerable group had worse performance on FAS verbal fluency, generating 4.1 fewer words (95% CI: 1.8-6.4, p<0.001) than those in the least socially vulnerable group; those with intermediate social vulnerability generated 2.6 fewer words (95% CI: 0.4-4.8, p = 0.02). Social vulnerability was also associated, though less strongly, with category verbal fluency. The most socially vulnerable people had impaired performance on the Trails B, taking 37 seconds longer (95% CI: 11-63, p = 0.005). These results were independent of age, education, sex, frailty, MMSE score, depression, and psychoactive medications. Social vulnerability was not associated with performance on WAIS-R abstraction, WAIS-R comprehension, Block Design, Token Test or Wechsler Memory Scale tests. High social vulnerability was associated with impaired performance on verbal fluency and set shifting but not with common sense judgment, abstraction, long-term memory, constructional ability, or language comprehension. The association between social functioning and the cognitive functions subserved by prefrontal cortex warrants further study.

Alzheimer's disease and frontal variant of frontotemporal dementia

The aim of this study was to investigate whether a brief neuropsychological battery consisting of a limited number of cognitive tests and an evaluation of the behavioural domains intended to discriminate between frontotemporal dementia (fv-FTD) and Alzheimer's disease (AD), constitutes a useful instrument for making a differential clinical diagnosis between these two pathologies. Nineteen fv-FTD and 39 AD patients were compared on cognitive tasks (assessing memory, executive functions, language and constructional praxis) and on the NPI behavioural assessment. A stepwise discriminant analysis was performed to identify the linear combination of cognitive and behavioural measures able to best discriminate between the two groups. One test for each of the investigated cognitive domains (Delayed Prose Recall, FAS verbal fluency, Boston naming test, Rey's Figure A Copy) and the four subscales of the Neuropsychiatry Inventory (NPI) which best differentiated between fv-FTD and AD patients (apathy, disinhibition, euphoria, aberrant motor behaviour) were used. The analysis selected Rey's Figure A Copy, FAS verbal fluency and NPI apathy subscale as the best discriminants between fv-FTD and AD patients. The final equation assigned 73.7% of the fv-FTD patients and 94.7% of the AD patients to the correct diagnostic group. A validation study conducted on a new independent sample of 11 fv-FTD and 22 AD patients confirmed the high sensitivity (82.6 %) and specificity (81.8%) of the diagnostic equation in assigning fv-FTD and AD patients to the correct dementia group. Although both cognitive and behavioural differences exist between FTD and AD, previous studies have aimed at differentiating the two pathologies by considering the two aspects separately and discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. The present results emphasise the importance of rating both cognitive and behavioural clinical features of the two syndromes as objectively as possible to improve differential diagnostic accuracy.

Parietal lobe activation in rapid, automatized naming by adults.

Three automatic naming tasks (Wiig & Nielsen, 1999) were administered to 60 normally functioning adults. The mean time required for naming 40 single-dimension (colors, forms, numbers, and letters) and 40 dual-dimension stimuli (color-form, color-number, and color-letter combinations) were compared in young (17-38 yr.) and older (40-68 yr.) men and women. Analysis of variance for the combined groups indicated significant naming-time differences for age but not for sex. There were no significant interaction effects. For men there was a significant naming time difference between age groups for forms, and for women for colors and forms. The sex-specific analyses indicated no significant differences in naming time based on age groups for color-form, color-number, or color-letter combinations. In a second study of adult subjects (n = 14), functional brain activity was measured with regional cerebral blood flow during the performance of the color, form, and color-form naming tasks. One subject was repeatedly measured during the performance of each task, whereas 13 subjects were measured during the performance of color-form naming. In comparison to normal reference values for rest and FAS verbal fluency, blood-flow measurements showed a consistent parietal-lobe activation during form and color-form naming, but only a slight activation during color naming. During all naming tasks, a significant frontal and frontotemporal flow decrease was seen in comparison to both rest and verbal fluency reference values. This functional brain activation pattern of a parietal increase and a frontotemporal decrease was consistently confirmed across subjects during the color-form naming task.

Nithsdale Schizophrenia Surveys 20

Cognitive deficits are a core aspect of schizophrenia but there has been no study of cognitive function in a catchment-area-based population of patients with schizophrenia. To assess cognitive function in a population of patients with schizophrenia, and relate it to community functioning. All patients with schizophrenia in Nithsdale, south-west Scotland, were identified (n = 182). Measures of assessment were: National Adult Reading Test (NART), Mini-Mental State Examination (MMSE), Rivermead Behavioural Memory Test (RBMT), Executive Interview (EXIT), FAS Verbal Fluency and Health of the Nation Outcome Scales (HoNOS). We assessed 138 patients, mean age 48 years (standard deviation (s.d.) 15). Only 14% were in-patients. The mean premorbid IQ as assessed by NART was 98 (s.d. 14); 15% of patients had significant global cognitive impairment (MMSE); 81% had impaired memory (RBMT); 25% had executive dyscontrol (EXIT); and 49% had impaired verbal fluency (FAS). Scores on the functional impairment sub-scale of HoNOS correlated with all measures of cognitive impairment. Cognitive dysfunction is pervasive in a community-based population of patients with schizophrenia.

Verbal fluency task equivalence

Abstract The research and clinical use of the verbal fluency paradigm has been hindered by the paucity of information on the equivalency of the various versions of this measure. Currently, the comparability of the two most commonly used forms of the letter fluency task, the “FAS” and “CFL” tests, is uncertain. The equivalence of these versions was investigated by examining their consistency across and within settings and disease processes. The two verbal fluency tasks were administered to 287 patients at two separate sites as part of a neuropsychological evaluation. Results showed that the CFL and FAS verbal fluency paradigms were equivalent across both settings and diagnostic groups with correlations ranging from .87 to .94. These findings may be useful for both researchers and clinicians who require equivalent measures for repeated testing. Furthermore, the demonstrated equivalency of the two paradigms may facilitate interpretation of research findings across laboratories.