Calculation of the Hadronic Vacuum Polarization Contribution to the Muon Anomalous Magnetic Moment.

We present a first-principles lattice QCD+QED calculation at physical pion mass of the leading-order hadronic vacuum polarization contribution to the muon anomalous magnetic moment. The total contribution of up, down, strange, and charm quarks including QED and strong isospin breaking effects is a_{µ}^{HVP LO}=715.4(18.7)×10^{-10}. By supplementing lattice data for very short and long distances with R-ratio data, we significantly improve the precision to a_{µ}^{HVP LO}=692.5(2.7)×10^{-10}. This is the currently most precise determination of a_{µ}^{HVP LO}.

Calculation of the Hadronic Vacuum Polarization Disconnected Contribution to the Muon Anomalous Magnetic Moment.

We report the first lattice QCD calculation of the hadronic vacuum polarization (HVP) disconnected contribution to the muon anomalous magnetic moment at physical pion mass. The calculation uses a refined noise-reduction technique that enables the control of statistical uncertainties at the desired level with modest computational effort. Measurements were performed on the 48^{3}×96 physical-pion-mass lattice generated by the RBC and UKQCD Collaborations. We find the leading-order hadronic vacuum polarization a_{µ}^{HVP(LO)disc}=-9.6(3.3)(2.3)×10^{-10}, where the first error is statistical and the second systematic.

Standard Model Prediction for Direct CP Violation in K→ππ Decay.

We report the first lattice QCD calculation of the complex kaon decay amplitude A_{0} with physical kinematics, using a 32³×64 lattice volume and a single lattice spacing a, with 1/a=1.3784(68) GeV. We find Re(A_{0})=4.66(1.00)(1.26)×10(-7) GeV and Im(A_{0})=-1.90(1.23)(1.08)×10(-11) GeV, where the first error is statistical and the second systematic. The first value is in approximate agreement with the experimental result: Re(A_{0})=3.3201(18)×10(-7) GeV, while the second can be used to compute the direct CP-violating ratio Re(ϵ^{'}/ϵ)=1.38(5.15)(4.59)×10^{-4}, which is 2.1σ below the experimental value 16.6(2.3)×10(-4). The real part of A_{0} is CP conserving and serves as a test of our method while the result for Re(ϵ^{'}/ϵ) provides a new test of the standard model theory of CP violation, one which can be made more accurate with increasing computer capability.

Emerging understanding of the ΔI=1/2 rule from lattice QCD.

There has been much speculation as to the origin of the ΔI=1/2 rule (ReA0/ReA2≃22.5). We find that the two dominant contributions to the ΔI=3/2, K→ππ correlation functions have opposite signs, leading to a significant cancelation. This partial cancelation occurs in our computation of ReA2 with physical quark masses and kinematics (where we reproduce the experimental value of A2) and also for heavier pions at threshold. For ReA0, although we do not have results at physical kinematics, we do have results for pions at zero momentum with mπ≃420 MeV [ReA0/ReA2=9.1(2.1)] and mπ≃330 MeV [ReA0/ReA2=12.0(1.7)]. The contributions which partially cancel in ReA2 are also the largest ones in ReA0, but now they have the same sign and so enhance this amplitude. The emerging explanation of the ΔI=1/2 rule is a combination of the perturbative running to scales of O(2 GeV), a relative suppression of ReA2 through the cancelation of the two dominant contributions, and the corresponding enhancement of ReA0. QCD and electroweak penguin operators make only very small contributions at such scales.

Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies.

Lewy bodies are common in the ageing brain and often co-occur with Alzheimer's disease pathology. There is little known regarding the independent role of Lewy body pathology in cognition impairment, decline and fluctuations in community-dwelling older persons. We examined the contribution of Lewy body pathology to dementia, global cognition, cognitive domains, cognitive decline and fluctuations in 872 autopsied subjects (mean age = 87.9 years) from the Rush Religious Order Study (n = 491) and Memory and Aging Project (n = 381) longitudinal community-based clinical-pathological studies. Dementia was based on a clinical evaluation; annual cognitive performance tests were used to create a measure of global cognition and five cognitive domains. Lewy body type was determined by using α-synuclein immunostained sections of substantia nigra, limbic and neocortical regions. Statistical models included multiple regression models for dementia and cognition and mixed effects models for decline. Cognitive fluctuations were estimated by comparing standard deviations of individual residuals from mean trajectories of decline in those with and without Lewy bodies. All models controlled for age, sex, education, Alzheimer's disease pathology and infarcts. One hundred and fifty-seven subjects (18%) exhibited Lewy body pathology (76 neocortical-type, 54 limbic-type and 27 nigra-predominant). One hundred and three (66%) subjects with Lewy body pathology had a pathologic diagnosis of Alzheimer's disease. Neocortical-type, but not nigral-predominant or limbic-type Lewy body pathology was related to an increased odds of dementia (odds ratio = 3.21; 95% confidence interval = 1.78-5.81) and lower cognition (P < 0.001) including episodic memory function (P < 0.001) proximate to death. Neocortical-type Lewy body pathology was also related to a faster decline in global cognition (P < 0.001), decline in all five specific cognitive domains (all P-values < 0.001), and to fluctuations in decline of working and semantic memory (P-values < 0.001). Limbic-type Lewy body pathology was related to lower and faster decline in visuospatial skills (P = 0.042). The relationship of Lewy body pathology to cognition and dementia was not modified by Alzheimer's disease pathology. Neocortical-type Lewy body pathology is associated with increased odds of dementia; lower and more rapid decline in all cognitive domains including episodic memory and fluctuations in decline in semantic and working memory. Limbic-type Lewy body pathology is specifically associated with lower and more rapid decline in visuospatial skills. The effect of Lewy body pathology on cognition appears to be independent of Alzheimer's disease pathology.

K→(ππ)(I=2) decay amplitude from lattice QCD.

We report on the first realistic ab initio calculation of a hadronic weak decay, that of the amplitude A(2) for a kaon to decay into two π mesons with isospin 2. We find ReA(2)=(1.436±0.063(stat)±0.258(syst))10(-8) GeV in good agreement with the experimental result and for the hitherto unknown imaginary part we find ImA(2)=-(6.83±0.51(stat)±1.30(syst))10(-13) GeV. Moreover combining our result for ImA(2) with experimental values of ReA(2), ReA(0), and ε'/ε, we obtain the following value for the unknown ratio ImA(0)/ReA(0) within the standard model: ImA(0)/ReA(0)=-1.63(19)(stat)(20(syst)×10(-4). One consequence of these results is that the contribution from ImA(2) to the direct CP violation parameter ε' (the so-called Electroweak Penguin contribution) is Re(ε'/ε)(EWP)=-(6.52±0.49(stat)±1.24(syst))×10(-4). We explain why this calculation of A(2) represents a major milestone for lattice QCD and discuss the exciting prospects for a full quantitative understanding of CP violation in kaon decays.

Total daily physical activity and the risk of AD and cognitive decline in older adults.

OBJECTIVE: Studies examining the link between objective measures of total daily physical activity and incident Alzheimer disease (AD) are lacking. We tested the hypothesis that an objective measure of total daily physical activity predicts incident AD and cognitive decline. METHODS: Total daily exercise and nonexercise physical activity was measured continuously for up to 10 days with actigraphy (Actical®; Philips Healthcare, Bend, OR) from 716 older individuals without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. All participants underwent structured annual clinical examination including a battery of 19 cognitive tests. RESULTS: During an average follow-up of about 4 years, 71 subjects developed clinical AD. In a Cox proportional hazards model adjusting for age, sex, and education, total daily physical activity was associated with incident AD (hazard ratio = 0.477; 95% confidence interval 0.273-0.832). The association remained after adjusting for self-report physical, social, and cognitive activities, as well as current level of motor function, depressive symptoms, chronic health conditions, and APOE allele status. In a linear mixed-effect model, the level of total daily physical activity was associated with the rate of global cognitive decline (estimate 0.033, SE 0.012, p = 0.007). CONCLUSIONS: A higher level of total daily physical activity is associated with a reduced risk of AD.

Terminal dedifferentiation of cognitive abilities.

OBJECTIVE: To test the cognitive dedifferentiation hypothesis that cognitive abilities become increasingly correlated in late life. METHODS: Participants are 174 older persons without dementia at the beginning of a longitudinal clinical-pathologic cohort study. At annual intervals for 6 to 15 years prior to death, they completed a battery of cognitive performance tests from which previously established composite measures of episodic memory, semantic memory, working memory, and perceptual speed were derived. At death, there was a uniform neuropathologic assessment and levels of diffuse plaques, neuritic plaques, and neurofibrillary tangles were summarized in a composite measure. Change in the 4 cognitive outcomes was analyzed simultaneously in a mixed-effects model that allowed rate of decline to accelerate at a variable point before death. RESULTS: On average, cognitive decline before the terminal period was relatively gradual, and rates of change in different cognitive domains were moderately correlated, ranging from 0.25 (episodic memory-working memory) to 0.46 (episodic memory-semantic memory). By contrast, cognition declined rapidly during the terminal period, and rates of change in different cognitive functions were strongly correlated, ranging from 0.83 (working memory-perceptual speed) to 0.89 (episodic memory-semantic memory, semantic memory-working memory). Higher level of plaques and tangles on postmortem examination was associated with faster preterminal decline and earlier onset of terminal decline but not with rate of terminal decline or correlations between rates of change in different cognitive functions. CONCLUSION: In the last years of life, covariation among cognitive abilities sharply increases consistent with the cognitive dedifferentiation hypothesis.

Cognitive activity and the cognitive morbidity of Alzheimer disease.

OBJECTIVE: To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter. METHODS: As part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals. RESULTS: On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale. CONCLUSION: Mentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.

Neurodegenerative basis of age-related cognitive decline.

OBJECTIVE: To assess the contribution of dementia-related neuropathologic lesions to age-related and disease-related change in cognitive function. METHODS: A total of 354 Catholic nuns, priests, and brothers had annual clinical evaluations for up to 13 years, died, and underwent brain autopsy. The clinical evaluations included detailed testing of cognitive function from which previously established composite measures of global cognition and specific cognitive functions were derived. As part of a uniform neuropathologic evaluation, the density of neurofibrillary tangles was summarized in a composite measure and the presence of Lewy bodies and gross and microscopic cerebral infarction was noted. RESULTS: During follow-up, rate of global cognitive decline was gradual at first and then more than quadrupled in the last 4 to 5 years of life consistent with the onset of progressive dementia. Neurofibrillary tangles, cerebral infarction, and neocortical Lewy bodies all contributed to gradual age-related cognitive decline and little age-related decline was evident in the absence of these lesions. Neurofibrillary tangles and neocortical Lewy bodies contributed to precipitous disease-related cognitive decline, but substantial disease-related decline was evident even in the absence of these lesions. CONCLUSION: Mild age-related decline in cognitive function is mainly due to the neuropathologic lesions traditionally associated with dementia.

Kidney function is associated with the rate of cognitive decline in the elderly.

OBJECTIVE: We tested the hypothesis that impaired kidney function in the elderly is associated with a more rapid rate of cognitive decline. METHODS: Baseline serum was used to calculate estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula, for 886 elderly without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. Kidney function was also dichotomized into impairment or no impairment based on eGFR < or >or=60 mL/min/1.73 m(2). Structured cognitive testing was performed at baseline and at annual evaluations, using a battery of 19 cognitive tests summarized into global cognition and 5 cognitive domains. RESULTS: In mixed-effects models adjusted for age, sex, and education, a lower eGFR at baseline was associated with a more rapid rate of cognitive decline (estimate 0.0008, SE <0.001, p = 0.017). The increased rate of cognitive decline associated with a 15-mL/min/1.73 m(2) lower eGFR at baseline (approximately 1 SD) was similar to the effect of being 3 years older at baseline. Impaired kidney function at baseline was associated with a more rapid rate of cognitive decline (estimate -0.028, SE <0.009, p = 0.003). The increased rate of cognitive decline associated with impaired kidney function at baseline was approximately 75% the effect of ApoE4 allele on the rate of cognitive decline. Baseline kidney function was associated with declines in semantic memory, episodic memory, and working memory but not visuospatial abilities or perceptual speed. CONCLUSION: Impaired kidney function is associated with a more rapid rate of cognitive decline in old age.

UKQCD software for lattice quantum chromodynamics.

Quantum chromodynamics (QCD) is the quantum field theory of the strong nuclear interaction and it explains how quarks and gluons are bound together to make more familiar objects such as the proton and neutron, which form the nuclei of atoms. UKQCD is a collaboration of eight UK universities that have come together to obtain and pool sufficient resources, both computational and manpower, to perform lattice QCD calculations. This paper explains how UKQCD uses and develops this software, how performance critical kernels for diverse architectures such as quantum chromodynamics-on-a-chip, BlueGene and XT4 are developed and employed and how UKQCD collaborates both internally and externally, with, for instance, the US SciDAC lattice QCD community.

Respiratory muscle strength predicts decline in mobility in older persons.

OBJECTIVES: To test the hypothesis that respiratory muscle strength is associated with the rate of change in mobility even after controlling for leg strength and physical activity. METHODS: Prospective study of 890 ambulatory older persons without dementia who underwent annual clinical evaluations to examine change in the rate of mobility over time. RESULTS: In a linear mixed-effect model adjusted for age, sex, and education, mobility declined about 0.12 unit/year, and higher levels of respiratory muscle strength were associated with a slower rate of mobility decline (estimate 0.043, SE 0.012, p < 0.001). Respiratory muscle strength remained associated with the rate of change in mobility even after controlling for lower extremity strength (estimate 0.036, SE 0.012, p = 0.004). In a model that included terms for respiratory muscle strength, lower extremity strength and physical activity together, all three were independent predictors of mobility decline in older persons. These associations remained significant even after controlling for body composition, global cognition, the development of dementia, parkinsonian signs, possible pulmonary disease, smoking, joint pain and chronic diseases. CONCLUSION: Respiratory muscle strength is associated with mobility decline in older persons independent of lower extremity strength and physical activity. Clinical interventions to improve respiratory muscle strength may decrease the burden of mobility impairment in the elderly.

Pulmonary function, muscle strength and mortality in old age.

Numerous reports have linked extremity muscle strength with mortality but the mechanism underlying this association is not known. We used data from 960 older persons without dementia participating in the Rush Memory and Aging Project to test two sequential hypotheses: first, that extremity muscle strength is a surrogate for respiratory muscle strength, and second, that the association of respiratory muscle strength with mortality is mediated by pulmonary function. In a series of proportional hazards models, we first demonstrated that the association of extremity muscle strength with mortality was no longer significant after including a term for respiratory muscle strength, controlling for age, sex, education, and body mass index. Next, the association of respiratory muscle strength with mortality was attenuated by more than 50% and no longer significant after including a term for pulmonary function. The findings were unchanged after controlling for cognitive function, parkinsonian signs, physical frailty, balance, physical activity, possible COPD, use of pulmonary medications, vascular risk factors including smoking, chronic vascular diseases, musculoskeletal joint pain, and history of falls. Overall, these findings suggest that pulmonary function may partially account for the association of muscle strength and mortality.

Kl3 semileptonic form factor from (2+1)-flavor lattice QCD.

We present the first results for the K13 form factor from simulations with 2+1 flavors of dynamical domain wall quarks. Combining our result, namely, f+(0)=0.964(5) with the latest experimental results for Kl3 decays leads to |V us|=0.2249(14), reducing the uncertaintity in this important parameter. For the O(p6) term in the chiral expansion we obtain Delta f=-0.013(5).

Processing resources reduce the effect of Alzheimer pathology on other cognitive systems.

UNLABELLED: The cognitive abilities of older persons vary greatly, even among those with similar amounts of Alzheimer disease (AD) pathology, suggesting differences in neural reserve. Although its neurobiologic basis is not well understood, reserve may reflect differences in the ability to compensate for the deleterious effects of pathology by recruiting alternative or additional brain networks to perform a specific task. If this is an effective compensatory strategy, then involvement of additional cognitive systems may help maintain function in other cognitive systems despite the accumulation of pathology. OBJECTIVE: We tested the hypothesis that processing resources, specifically perceptual speed and working memory, modify the associations of AD pathology with other cognitive systems. METHOD: A total of 103 older participants of the Rush Memory and Aging Project underwent detailed annual clinical evaluations and brain autopsy. Five cognitive systems including perceptual speed, working memory, semantic memory, visuospatial abilities, and episodic memory were assessed proximate to death, and AD pathology including tau tangles and amyloid load were quantified postmortem. RESULTS: In multiple regression models adjusted for age, sex, and education, processing resources reduced the associations of tangles with other cognitive systems, such that persons with higher levels of perceptual speed and working memory performed better on semantic memory and visuospatial abilities despite the burden of tangles. Perceptual speed also reduced the associations of amyloid with semantic memory, visuospatial abilities, and episodic memory. CONCLUSION: These findings suggest that processing resources may help compensate for the deleterious effects of Alzheimer disease pathology on other cognitive systems in older persons.

Neutral-kaon mixing from (2+1)-flavor domain-wall QCD.

We present the first results for neutral-kaon mixing using (2+1)-flavors of domain-wall fermions. A new approach is used to extrapolate to the physical up and down quark masses from our numerical studies with pion masses in the range 240-420 MeV; only SU(2)_{L}xSU(2)_{R} chiral symmetry is assumed and the kaon is not assumed to be light. Our main result is B_{K};{MS[over ]}(2 GeV)=0.524(10)(28) where the first error is statistical and the second incorporates estimates for all systematic errors.

Chronic distress and incidence of mild cognitive impairment.

OBJECTIVE: Mild cognitive impairment (MCI) is associated with increased morbidity and mortality but its development is not well understood. Here we test the hypothesis that chronic psychological distress is associated with increased incidence of MCI in old age. METHODS: Participants are older persons from two cohort studies with uniform annual clinical evaluations which included detailed cognitive testing and clinical classification of MCI. We excluded persons with dementia or MCI at baseline; follow-up data were available on 1,256 persons without cognitive impairment (95% of those eligible). At baseline, they completed a six-item measure of neuroticism (mean = 15.6, SD = 6.6), an indicator of the tendency to experience psychological distress. RESULTS: During up to 12 years of follow-up, 482 persons (38%) developed MCI. Risk of MCI increased by about 2% for each one unit increase on the distress scale (relative risk [RR] = 1.02; 95% CI: 1.01, 1.04), with the association slightly stronger in men than women. Overall, a distress-prone person (score = 24, 90th percentile) was about 40% more likely to develop MCI than someone not prone to distress (score = 8, 10th percentile). Adjustment for depressive symptomatology at baseline did not substantially change results (RR = 1.02; 95% CI: 1.00, 1.03). Depressive symptoms were also related to risk of MCI but not after controlling for distress score. In mixed-effects models, higher distress score was associated with lower level of function in multiple cognitive domains at baseline and more rapid cognitive decline, especially in episodic memory. CONCLUSION: Among older persons without manifest cognitive impairment, higher level of chronic psychological distress is associated with increased incidence of mild cognitive impairment.

Lower extremity motor function and disability in mild cognitive impairment.

Recent findings suggest that lower extremity motor dysfunction may be a feature of mild cognitive impairment (MCI), but little is known about the nature and significance of lower extremity motor dysfunction in MCI. The aim of this study was to examine the extent to which MCI is associated with impaired gait, balance, and strength and to examine the relation of lower extremity function to disability among persons with MCI in the Rush Memory and Aging Project, a clinical-pathologic study of common chronic conditions of old age. In a series of analyses adjusted for age, sex, and education, individuals with MCI exhibited more impaired gait and balance than individuals without cognitive impairment. Because vascular factors can contribute to lower extremity motor dysfunction, the authors repeated the initial analyses including terms for vascular risk factors and vascular disease, and the associations between MCI and lower extremity motor dysfunction persisted. Moreover, among those with MCI, impairments in gait and balance were associated with an increased likelihood of disability. These findings suggest that lower extremity motor dysfunction is common and contributes to disability in MCI, but lower extremity motor dysfunction in MCI does not appear to be explained by the vascular factors examined in this study.