Global Cognitive Z-score Research Articles

The Mediterranean Diet and Two-Year Changes in Cognitive Function in Puerto Rican Adults With vs. Without Type 2 Diabetes

People with type 2 diabetes (T2D), especially uncontrolled T2D, have high risk of cognitive decline. The role of a Mediterranean diet on cognitive function has not been assessed for adults with vs. without T2D within the same population. We aimed to determine associations of a Mediterranean diet score (MeDS) with 2 year changes in cognitive function by T2D status and by glycemic control status. We used data from the Boston Puerto Rican Health Study (mean (SD) age= 57.2 (7.6) y; n=711 without T2D; n=465 with T2D defined as fasting plasma glucose ≥ 126 mg/dL or medication use). Glycemic control at baseline was categorized as uncontrolled (hemoglobin A1c ≥7%; 74% of T2D sample)) vs. controlled (26%). Two-y changes in glycemic control were defined as stable/improved (32%) vs. poor/declined (68%). Baseline MeDS ranged from 0-9 by scoring participants within the sex-specific healthy median intake of 9 foods and nutrients. The primary outcome was 2 year change in global cognitive function z-score, which included 7 cognitive tests. Adjusting for baseline sociodemographic and lifestyle factors, comorbidities, and baseline measure, MeDS was positively associated with 2 year change in global cognitive function in adults with T2D (β ± SE=0.027 ± 0.011; p=0.016) but not without T2D (-0.002 ± 0.008; p=0.80). Similar results were noted for single cognitive tests (i.e., mini-mental state examination, word recognition, digit span, clock drawing). Better global cognitive function over 2 years with higher MeDS was noted with glycemic control at baseline (0.062 ± 0.020; p=0.004) or stable/improved over 2 years (0.053 ± 0.019; p=0.007), but not for uncontrolled or poor/declined glycemic control. Adhering to a Mediterranean diet is associated with positive 2 year changes in cognitive function among adults with T2D. Glycemic control further sustains these benefits, suggesting that both a healthy Mediterranean diet and effective clinical management may help preserve optimal cognitive function in adults with T2D. Disclosure J. Mattei: None. S.J. Bigornia: None. M. Sotos-Prieto: None. T. Scott: None. X. Gao: None. K.L. Tucker: None.

Global cerebrovascular burden and long-term clinical outcomes in Asian elderly across the spectrum of cognitive impairment.

A case-control study was conducted over a 2-year period involving participants with no cognitive impairment, cognitive impairment-no dementia (CIND), and Alzheimer's disease (AD). Annually, cognitive function was assessed with a comprehensive neuropsychological battery and the clinical dementia rating (CDR) scale was used to stage disease severity. Of 314 participants, 102 had none/very mild CeVD, 31 mild CeVD, 94 moderate CeVD, and 87 severe CeVD at baseline. There was a 1.14 and 1.42 units decline per year on global cognitive z-scores in moderate and severe CeVD groups, respectively, compared to none/very mild CeVD. Moderate-severe CeVD predicted significant functional deterioration at year 2 (HR = 2.0, 95% CI = 1.2-3.4), and conversion to AD (HR = 6.3, 95% CI = 1.7-22.5), independent of medial temporal atrophy. The global CeVD burden scale predicts poor long-term clinical outcome independent of neurodegenerative markers. Furthermore, CeVD severity affects the rate of cognitive and functional deterioration. Hence, cerebrovascular burden, which is potentially preventable, is a strong prognostic indicator, both at preclinical and clinical stages of AD, independent of neurodegenerative processes.

Plasma Concentrations of Lutein and Zeaxanthin, Macular Pigment Optical Density, and Their Associations With Cognitive Performances Among Older Adults

We investigated the cross-sectional associations between macular pigment optical density (MPOD), plasma lutein (L), and zeaxanthin (Z) concentrations and cognitive function in 184 older adults of the 3-City-Bordeaux cohort. MPOD was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma L and Z (L+Z) concentrations were determined by high-performance liquid chromatography and were considered either crude or expressed as a ratio of the concentration of plasma lipids (total cholesterol [TC] + triglycerides [TG]). Cognitive performances were assessed using the following four separate neuropsychological tests: the Mini-Mental State Examination (MMSE), the Isaacs Set Test (IST), the Benton Visual Retention Test (BVRT), and the sum of the three free recalls of the Free and Cued Selective Reminding Test (FCSRT). These test results were summarized by a composite global cognitive z-score. Higher MPOD at 0.5° was significantly associated with a higher composite z-score (β = 0.15, 95% confidence interval [CI] 0.04-0.26), higher BVRT (β = 0.39, 95%CI 0.08-0.70), and higher IST (β = 1.16, 95%CI 0.11-2.22) performances. Higher plasma L+Z concentrations were significantly associated with higher IST scores (β = 0.97, 95%CI 0.01-1.94). Furthermore, a higher L+Z/TC+TG ratio was associated with a higher composite z-score (β = 0.12, 95%CI 0.01-0.23), along with higher IST (β = 1.02, 95%CI 0.002-2.04) and FCSRT (β = 1.55, 95%CI 0.41-2.69) performances. This analysis suggested that both higher MPOD and L+Z concentrations were significantly associated with higher cognitive performances. However, MPOD measurements have the advantage of being a fast and representative measure of long-term carotenoid intake.

Association of Atrial Fibrillation With Cognitive Decline and Dementia Over 20Years: The ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study).

BackgroundPrevious studies have reported that atrial fibrillation (AF) is associated with cognitive decline and dementia. These studies, however, had limited follow‐up, were based mostly on white and highly selected populations, and did not account for attrition. We evaluated the association of incident AF with 20‐year change in cognitive performance (accounting for attrition) and incident dementia in the ARIC (Atherosclerosis Risk in Communities) Study.Methods and ResultsWe analyzed data from 12 515 participants (mean age, 56.9 [SD, 5.7] years in 1990–1992; 56% women and 24% black) from 1990 to 1992 through 2011 to 2013. Incident AF was ascertained from study ECGs and hospital discharge codes. Cognitive tests were performed in 1990 to 1992, 1996 to 1998, and 2011 to 2013. Incident dementia was clinician adjudicated. We used generalized estimating equations and Cox proportional hazards models to assess the association of time‐dependent AF with change in Z scores of cognitive tests and incident dementia, respectively. During 20 years, 2106 participants developed AF and 1157 participants developed dementia. After accounting for cardiovascular risk factors, including ischemic stroke, the average decline over 20 years in global cognitive Z score was 0.115 (95% confidence interval, 0.014–0.215) greater in participants with AF than in those without AF. Further adjustment for attrition by multiple imputation by chained equations strengthened the association. In addition, incident AF was associated with an increased risk of dementia (hazard ratio, 1.23; 95% confidence interval, 1.04–1.45), after adjusting for cardiovascular risk factors, including ischemic stroke.Conclusions AF is associated with greater cognitive decline and increased risk of dementia, independent of ischemic stroke. Because cognitive decline is a precursor to dementia, our findings prompt further investigation to identify specific treatments for AF that will delay the trajectory of cognitive decline and, thus, prevent dementia in patients with AF.

Executive function and other cognitive deficits are distal risk factors of generalized anxiety disorder 9 years later.

The cognitive model (Hirsch & Mathews, 2012) and attentional control theory (Eysenck & Derakshan, 2011) postulate that compromised executive function (EF) and other cognitive constructs are negatively linked to increased excessive and uncontrollable worry, the core symptom of generalized anxiety disorder (GAD). However, the prospective link between neuropsychological constructs and GAD are not well understood. A nationally representative sample of 2605 community-dwelling adults whose average age was 55.20 (s.d. = 11.41, range 33-84; 56.31% females) participated at baseline and 9-year follow-up. Baseline neuropsychological function and symptoms were measured using the Brief Test of Adult Cognition by Telephone and Composite International Diagnostic Interview - Short Form. Multivariate Poisson and negative binomial regression analyses were conducted with 11 baseline covariates entered simultaneously: age, gender, years of formal education, perceived control, hypertension/diabetes, body mass index, exercise status, as well as GAD severity, panic disorder severity, and depression severity. Those with baseline GAD were also removed. Lower Time 1 composite global cognition z-score independently predicted higher Time 2 GAD severity and diagnosis [odds ratio (OR) 0.60, 95% confidence interval (CI) 0.40-0.89, p = 0.01]. Poor inhibition, set-shifting, working memory (WM) updating, inductive reasoning, and global cognition sequentially forecasted heightened GAD. However, processing speed, verbal WM, verbal fluency, and episodic memory did not predict future GAD. Global cognition, inductive reasoning, inhibition, set-shifting, and WM updating EF impairments may be distal risk factors for elevated GAD nearly a decade later.

Color discrimination errors associate with axial motor impairments in Parkinson's disease.

Visual function deficits are more common in imbalance-predominant compared to tremor-predominant PD suggesting a pathophysiological role of impaired visual functions in axial motor impairments. To investigate the relationship between changes in color discrimination and motor impairments in PD while accounting for cognitive or other confounder factors. PD subjects (n=49, age 66.7±8.3 years; Hoehn & Yahr stage 2.6±0.6) completed color discrimination assessment using the Farnsworth-Munsell 100 Hue Color Vision Test, neuropsychological, motor assessments and [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 PET imaging. MDS-UPDRS sub-scores for cardinal motor features were computed. Timed up and go mobility and walking tests were assessed in 48 subjects. Bivariate correlation coefficients between color discrimination and motor variables were significant only for the Timed up and go (RS=0.44, P=0.0018) and the MDS-UPDRS axial motor scores (RS=0.38, P=0.0068). Multiple regression confounder analysis using the Timed up and go as outcome parameter showed a significant total model (F(5,43)= 7.3, P<0.0001) with significant regressor effects for color discrimination (standardized β=0.32, t=2.6, P=0.012), global cognitive Z-score (β=-0.33, t=-2.5, P=0.018), duration of disease (β=0.26, t=1.8, P=0.038), but not for age or striatal dopaminergic binding. The color discrimination test was also a significant independent regressor in the MDS-UPDRS axial motor model (standardized β=0.29, t=2.4, P=0.022; total model t(5,43)= 6.4, P=0.0002). Color discrimination errors associate with axial motor features in PD independent of cognitive deficits, nigrostriatal dopaminergic denervation, and other confounder variables. These findings may reflect shared pathophysiology between color discrimination visual impairments and axial motor burden in PD.

Relationships of Clinical and Computed Tomography-Imaged Adiposity with Cognition in Middle-Aged and Older African Americans.

Adiposity depots may differentially affect cognition. African Americans (AA) have higher rates of obesity and dementia but lower visceral adipose tissue (VAT) than whites, yet are underrepresented in studies of adiposity and cognition. Our study compared relations of cognitive function to clinical adiposity measures and computed tomography (CT)-imaged abdominal adiposity in AA. CT-imaged subcutaneous adipose tissue (SAT) and VAT measurements were obtained in the AA cohort of the Genetic Epidemiology Network of Arteriopathy Study (N = 652, mean age 68 ± 8.4 years, 74% females, 59% obese, 82% hypertensive). Clinical adiposity measures included waist circumference (WC) and body mass index (BMI). Global cognition was operationalized as a global cognitive z-score generated from the average of four cognitive domain z-scores. Generalized estimating equations were used to examine cross-sectional associations between individual standardized adiposity measures and cognition, accounting for age, sex, education, smoking status, and familial clustering. A collective model was constructed including multiple supported adiposity measures and age-by-adiposity interactions. In the collective model, higher WC was associated with worse global cognition, β = -0.12 (95%CI: -0.21, -0.03); higher SAT was associated with better cognition, β = 0.09 (0.01, 0.18); higher BMI was associated with worse cognition at younger ages with attenuation at older ages (BMI-by-age-interaction p = .004). VAT was not significantly associated with global cognition, β = -0.03 (-0.07, 0.02). WC may be the simplest and most efficient measure of adiposity to assess with respect to cognition in clinical settings, although studies to determine mechanistic effects of subcutaneous and other adiposity depots on cognition are warranted.

Impaired contrast sensitivity is associated with more severe cognitive impairment in Parkinson disease

ObjectivesDopaminergic degeneration affects both nigrostriatal projection neurons and retinal amacrine cells in Parkinson disease (PD). Parkinsonian retinopathy is associated with impaired color discrimination and contrast sensitivity. Some prior studies described associations between color discrimination deficits and cognitive deficits in PD, suggesting that contrast discrimination deficits are due, at least in part, to cognitive deficits in PD. We investigated the relationship between cognitive deficits and impaired contrast sensitivity in PD. MethodsPD subjects, n = 43; 15F/28M; mean age 66.5 ± 8.2, Hoehn and Yahr stage 2.6 ± 0.6, and duration of disease of 6.2 ± 5.0 years underwent neuropsychological and Rabin contrast sensitivity testing. ResultsMean Rabin contrast sensitivity score was 1.34 ± 0.40. Bivariate analyses showed significant correlation between Rabin contrast sensitivity scores and global cognitive z-scores (R = 0.54, P = 0.0002). Cognitive domain Z-score post hoc analysis demonstrated most robust correlation between Rabin scores and executive functions (R = 0.49, P = 0.0009), followed by verbal learning (R = 0.44, P = 0.0028), visuospatial (R = 0.39, P = 0.001) and attention z-scores (R = 0.32, P = 0.036). ConclusionsImpaired contrast sensitivity in PD is robustly associated with cognitive deficits, particularly executive function deficits. These results suggest that contrast sensitivity may be a useful biomarker for cognitive changes in PD and may have implications for driving safety evaluations in PD.

APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals

BackgroundContinuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied. MethodsWe determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test. ResultsAn interquartile range (IQR:14.23μg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: −0.11 to −0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: −0.97 to −0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: −0.11, 95%CI: −0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele. ConclusionsOur findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.

Evolution of changes in cognitive function after the initiation of antiretroviral therapy.

BackgroundCognitive function is reported to improve after the initiation of combination antiretroviral therapy (cART). Data on the evolution of such changes are limited. We assessed the dynamics of changes in cognitive parameters, in HIV-positive subjects initiating cART.MethodsCognitive function in seven domains was evaluated for HIV-infected patients without clinically significant cognitive impairment prior to the initiation of cART, and 24 and 48 weeks after. Cognitive scores were transformed using standardised z-scores according to the pooled baseline standard deviation. Global, speed, and accuracy composite z-scores were calculated with changes calculated using a paired t test.ResultsIn 14 subjects, change in global cognitive z-scores from baseline was by 0.08 at week 24 (p = 0.59) and 0.15 at week 48 (p = 0.43). Change in composite speed and accuracy z-scores from baseline at weeks 24/48 were 0.07/0.05 (p = 0.45/0.82) and 0.13/0.23 (p = 0.47/0.45), respectively. In two of the cognitive domains assessing speed (learning and monitoring time), a continued improvement from baseline to weeks 24 and 48 was observed (changes of 0.06–0.08 and 0.10–0.19, respectively), whereas in two domains (detection and identification) an initial improvement at week 24 (changes of −0.10 and 0.04 from baseline, respectively) was followed by a deterioration in score at week 48 (changes of −0.12 and −0.08 from baseline, respectively). None of these changes were statistically significant.ConclusionsA trend for improvement in cognitive function was observed in naïve HIV-positive patients starting cART. The dynamics of this improvement differed both between cognitive domains and the time-points assessed.

Diabetes, Gray Matter Loss, and Cognition in the Setting of Parkinson Disease

Parkinson disease (PD) is a progressive neurodegenerative disorder affecting motor and cognitive functions. Prior studies showed that patients with PD and diabetes (DM) demonstrate worse clinical outcomes compared to nondiabetic subjects with PD. Our study aimed at defining the relationship between DM, gray matter volume, and cognition in patients with PD. This study included 36 subjects with PD (12 with DM, 24 without DM, mean age = 66). Subjects underwent high-resolution T1-weighted brain magnetic resonance imaging, [(11)C]dihydrotetrabenazine positron emission tomography imaging to quantify nigrostriatal dopaminergic denervation, clinical, and cognitive assessments. Magnetic resonance images were postprocessed to determine total and lobar cortical gray matter volumes. Cognitive testing scores were converted to z-scores for specific cognitive domains and a composite global cognitive z-score based on normative data computed. Analysis of covariance, accounting for effects of age, gender, intracranial volume, and striatal [(11)C]dihydrotetrabenazine binding, was used to test the relationship between DM and gray matter volumes. Impact of DM on total gray matter volume was significant (P = 0.02). Post hoc analyses of lobar cortical gray matter volumes revealed that DM was more selectively associated with lower gray matter volumes in the frontal regions (P = 0.01). Cognitive post hoc analyses showed that interaction of total gray matter volume and DM status was significantly associated with composite (P = 0.007), executive (P = 0.02), and visuospatial domain cognitive z-scores (P = 0.005). These associations were also significant for the frontal cortical gray matter. DM may exacerbate brain atrophy and cognitive functions in PD with greater vulnerability in the frontal lobes. Given the high prevalence of DM in the elderly, delineating its effects on patient outcomes in the PD population is of importance.

Risk Factors of Cognitive Impairment and Brief Cognitive Tests to Predict Cognitive Performance Determined by a Formal Neuropsychological Evaluation of Primary Health Care Patients

BackgroundCase finding for cognitive impairment (CI) is recommended for all persons older than 70 years. ObjectiveThe present study identified additional risk factors of CI so as to operationalize a composite total risk score (TRS) for case finding. We then examined the additive effect of the TRS and brief cognitive tests to improve the diagnosis of CI. MethodsThe study was conducted in 2 primary health care centers in Singapore. A total of 1082 individuals (≥60 years old) were assessed for sociodemographic risk factors and their informants were administered the AD8; 309 individuals who agreed for further cognitive assessments completed the Mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA), and a neuropsychological battery at a research center. Primary health care medical records were accessed for data on vascular risk factors. ResultsOf the 309 individuals who underwent neuropsychological evaluation, 4 were excluded due to missing medical data; 167 (54.8%) individuals had CI and 138 (45.2%) had No Cognitive Impairment (NCI). The β coefficients were standardized to calculate risk scores. CI was significantly predicted by age >70 years (odds ratio [OR] 5.99; score = 3), diabetes (OR 3.36; score = 2), stroke (OR 2.70; score = 1), female gender (OR 2.02; score = 1) and individual cognitive complaints (SCC) (OR 1.95; score = 1). The TRS had an optimal cutoff of ≥3 and explained considerable variance in global cognitive composite Z-scores (R2 = 0.41, P < .001). The MoCA explained substantial variance compared with the MMSE and AD8 (R2 changes of 0.474, 0.422, and 0.157, P < .001, respectively). ConclusionThe TRS is a reasonable measure to predict individuals at risk of CI. The addition of the MoCA, in persons with positive TRS scores, is a useful approach to improve the diagnosis of CI for at-risk patients attending primary health care.

Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly.

Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with both vascular and amyloid pathologies, the effect of both pathologies on cognition was additive and not synergistic. For a 79-year-old subject, the predicted annual rate of global z-score decline was -0.02 if on neither pathway, -0.07 if on the vascular pathway, -0.08 if on the amyloid pathway and -0.13 if on both pathways. The main conclusions of this study were: (i) amyloid and vascular pathologies seem to be at least partly independent processes that both affect longitudinal cognitive trajectories adversely and are major drivers of cognitive decline in the elderly; and (ii) cognitive reserve seems to offset the deleterious effect of both pathologies on the cognitive trajectories.

Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease.

There is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied. To investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations. Cross-sectional study. Patients with PD (n=148); age 65.6±7.4 years, Hoehn and Yahr stage 2.4±0.6, with (n=15) and without (n=133) comorbid type II DM, underwent [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [(11)C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates. There were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (-0.98±1.01) compared to the non-diabetics (-0.36±0.91; F=7.78, P=0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F=8.39, P<0.0001). Diabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.

Assessing the Temporal Relationship Between Cognition and Gait: Slow Gait Predicts Cognitive Decline in the Mayo Clinic Study of Aging

The association between gait speed and cognition has been reported; however, there is limited knowledge about the temporal associations between gait slowing and cognitive decline among cognitively normal individuals. The Mayo Clinic Study of Aging is a population-based study of Olmsted County, Minnesota, United States, residents aged 70-89 years. This analysis included 1,478 cognitively normal participants who were evaluated every 15 months with a nurse visit, neurologic evaluation, and neuropsychological testing. The neuropsychological battery used nine tests to compute domain-specific (memory, language, executive function, and visuospatial skills) and global cognitive z-scores. Timed gait speed (m/s) was assessed over 25 feet (7.6 meters) at a usual pace. Using mixed models, we examined baseline gait speed (continuous and in quartiles) as a predictor of cognitive decline and baseline cognition as a predictor of gait speed changes controlling for demographics and medical conditions. Cross-sectionally, faster gait speed was associated with better performance in memory, executive function, and global cognition. Both cognitive scores and gait speed declined over time. A faster gait speed at baseline was associated with less cognitive decline across all domain-specific and global scores. These results were slightly attenuated after excluding persons with incident mild cognitive impairment or dementia. By contrast, baseline cognition was not associated with changes in gait speed. Our study suggests that slow gait precedes cognitive decline. Gait speed may be useful as a reliable, easily attainable, and noninvasive risk factor for cognitive decline.

P1‐122: Effect of lifestyle activities on Alzheimer's biomarkers and cognition

Intellectual and physical activities are increasingly viewed as possible preventive strategies for AD. The goal of this study was to investigate the association of intellectual and physical activity on biomarkers of Alzheimer's disease (AD) pathophysiology and cognition in a non-demented elderly population. The biomarkers evaluated were brain Aβ-amyloid load via PIB-PET, neuronal dysfunction via FDG-PET and neurodegeneration via Structural-MRI. We studied 515 non-demented (428 cognitively normal and 87 MCI) participants in the population based Mayo Clinic Study of Aging who completed a 3T MRI, PET scans, APOE genotype, had lifestyle activity measures and cognition data available. The imaging measures computed were global PiB-PET uptake; global FDG-PET and MRI based hippocampal volume. We consolidated activity variables into lifetime intellectual, current intellectual and current physical activities. We used a global cognitive Z-score as a measure of cognition. We applied two independent methods - partial correlation analysis adjusted for age and gender and path analysis using structural equations to evaluate the associations between lifestyle activities, imaging biomarkers and global cognition. None of the lifestyle variables correlated with the biomarkers and the path associations between lifestyle variables and biomarkers were not significant (p>0.05). On the other hand, all the biomarkers were correlated with global cognitive Z-score (P <0.05) and the path associations between (lifetime and current) intellectual activities and global Z-score were significant (P <0.01). Intellectual and physical activity lifestyle factors were not associated with AD biomarkers but intellectual lifestyle factors explained variability in the cognitive performance in this non-demented population. This study provides evidence that lifestyle activities may delay the onset of dementia but do not significantly influence the expression of AD pathophysiology. The key observations in this study are illustrated in Figure 1. Model illustrating the effect of lifestyle activities on AD biomarkers and cognition or clinical function in subjects. Clinical disease stage is indicated on the horizontal axis and the magnitude of biomarker abnormalities and cognition (from normal to maximally abnormal) on the vertical axis. The cognition or clinical function curve is moved left-right based on the individual's lifestyle activity. The variable λ for lifetime intellectual activity is greater than that for current intellectual activity and the variable λ for physical activity is close to zero.

Fish consumption and cognitive function among older people in the UK: baseline data from the OPAL study.

Observational epidemiological data suggest that habitual consumption in later life of oily fish, rich in n-3 long-chain polyunsaturated fatty acids (n-3 LCPs), is associated with better cognitive function, slower rates of cognitive decline and a lower risk of dementia. In this paper we present data on baseline fish consumption and cognitive function in cognitively healthy older people randomised onto the Older People And n- 3 Long-chain polyunsaturated fatty acid (OPAL) study. In total, 867 older people were recruited to join the OPAL study from 20 general practices in England and Wales. Participants were aged 70-79 years at baseline were free of dementia and diabetes, had a Mini-Mental State Examination score of 24 or greater and did not report daily fish oil supplement consumption. Self-reported habitual fish consumption was assessed at baseline via questions on frequency and type of fish consumption. Cognitive function at baseline was assessed via validated cognitive tests assessing memory, executive function, psychomotor speed and attention, including the Californian Verbal Learning Test (CVLT), the primary outcome of the OPAL study. Reported age at leaving full time education was recorded as a measure of educational achievement and psychological health was measured using the GHQ-30 questionnaire. Unadjusted analysis revealed significant positive associations between reported fish consumption and the CVLT scores with a mean increase of approximately 0.24 words remembered for each increase in level of reported fish consumption. These associations were noticeably attenuated on adjustment for age, gender and reported age at leaving full-time education and did not remain significant on further adjustment for GHQ-30 score. Similar associations were also observed between fish consumption and the global cognitive z-score, memory score, executive function score and delay scores in unadjusted analysis with the associations again attenuated on adjustment. Baseline data from participants randomised into the OPAL study provide support for the hypothesis that higher fish consumption is associated with better cognitive function in later life. However, although in the main associations remain after adjusting for education and psychological health, the data do not allow us to rule out the possibility of residual confounding e.g. from socioeconomic status or other health behaviours. Evidence is needed from randomised clinical trials to clarify the role of n-3 LCPs in cognitive health in later life in the normal older person population.

Effects of risperidone and quetiapine on cognition in patients with schizophrenia and predominantly negative symptoms

Evidence suggests that neurocognitive impairment is a key factor in the pathology of schizophrenia and is linked with the negative symptoms of the disease. In this study the effects of the atypical antipsychotics quetiapine and risperidone on cognitive function in patients with schizophrenia and with predominantly negative symptoms were compared. Patients were randomly assigned to double-blind treatment with quetiapine or risperidone for 12 weeks. Cognitive function was assessed at baseline, Week 6 and Week 12. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline, Week 6 and Week 12. Extrapyramidal side-effects were assessed each week using the Simpson-Angus Scale (SAS), adverse events were recorded as additional indicators of tolerability throughout the trial. In total, 44 patients were enrolled in the study. Data from the 34 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 6 and Week 12) are analysed here. Quetiapine improved significantly global cognitive index z-scores at both Week 6 (p<0.001 vs. baseline) and Week 12 (p<0.01 vs. baseline), whereas risperidone improved significantly global cognitive index z-scores at Week 12 (p<0.05). Between-group comparisons at Week 6 showed significantly greater improvements in working memory and verbal memory with quetiapine than risperidone (p<0.05) and a significantly greater improvement in reaction quality/attention with quetiapine than risperidone at Week 12 (p<0.05). Quetiapine and risperidone produced significant improvements from baseline in PANSS total (p<0.001) and subscale scores at Week 12. Significant improvements in SANS total score were also seen in both the quetiapine (p<0.001) and risperidone (p<0.01) groups at Week 12 compared with baseline. SAS scores, measuring the incidence of extrapyramidal side-effects, were higher in patients receiving risperidone compared with those receiving quetiapine, and significant differences were seen at Weeks 3, 4, 5 and 7. Both quetiapine and risperidone improved cognition according to changes in cognitive index scores from baseline to Week 12. These results suggest that quetiapine and risperidone provide valuable treatment options for patients with schizophrenia with predominantly negative symptoms. Also, the improvements in cognition following treatment with quetiapine and risperidone may enhance long-term outcomes for these patients.

Efficacy of olanzapine versus quetiapine on cognitive dysfunctions in patients with an acute episode of schizophrenia

Neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be relatively persistent towards psychopharmacological interventions. There are hints that atypical antipsychotics can influence neurocognitive dysfunctions more favorable than conventional compounds. But little is known about differences in efficacy on neurocognitive dysfunctions linked to the variety of receptor profiles of different atypical antipsychotics. This study compared the effects of the atypical antipsychotics quetiapine and olanzapine on cognitive function in patients with an acute episode of schizophrenia. Patients were randomized to receive quetiapine or olanzapine for 8 weeks. Cognitive function was assessed at baseline, week 4 and week 8. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Improvement Scale (CGI). Tolerability was assessed each week using the Extrapyramidal Symptom Rating Scale (ESRS), the Barnes Akathisia Scale (BAS) and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU). In total, 52 patients were enrolled in the study. Data from the 33 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 4 and Week 8) are analyzed here. Both quetiapine and olanzapine improved global cognitive index z-scores, however, this was more marked with quetiapine. Between-group comparisons showed significantly greater improvements in reaction quality/attention with quetiapine than olanzapine. Quetiapine and olanzapine produced significant improvements from baseline to week 8 in PANSS total and subscale scores. Both treatments were well tolerated, especially no EPS occurred during 8 weeks of treatment. Both quetiapine and olanzapine improved cognition; however, the improvement in cognitive index scores was more marked in patients receiving quetiapine. Furthermore, quetiapine produced a significantly greater improvement in reaction quality/attention than olanzapine.