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Introduction: A lack of physical activity (PA) is one of the most pressing health issues today. Our individual propensity for PA is influenced by genetic factors. Stated liking of different PA types may help capture additional and informative dimensions of PA behavior genetics., Methods: In over 157,000 individuals from the UK Biobank, we performed genome-wide association studies of five items assessing the liking of different PA types, plus an additional derived trait of overall PA-liking. We attempted to replicate significant associations in the Netherlands Twin Register (NTR) and TwinsUK. Additionally, polygenic scores (PGS) were trained in the UK Biobank for each PA-liking item and for self-reported PA behavior, and tested for association with PA in the NTR., Results: We identified a total of 19 unique significant loci across all five PA-liking items and the overall PA-liking trait, and these showed strong directional consistency in the replication cohorts. Four of these loci were previously identified for PA behavior, including CADM2 , which was associated with three PA-liking items. The PA-liking items were genetically correlated with self-reported ( rg = 0.38-0.80) and accelerometer ( rg = 0.26-0.49) PA measures, and with a wide range of health-related traits. Each PA-liking PGS significantly predicted the same PA-liking item in NTR. The PGS of liking for going to the gym predicted PA behavior in the NTR ( r2 = 0.40%) nearly as well as a PGS based on self-reported PA behavior ( r2 = 0.42%). Combining the two PGS into a single model increased the r2 to 0.59%, suggesting that PA-liking captures distinct and relevant dimensions of PA behavior., Conclusions: We have identified the first loci associated with PA-liking and extended our understanding of the genetic basis of PA behavior., (Copyright © 2022 by the American College of Sports Medicine.)

Introduction: Physical activity (PA) is recognized as one of the key lifestyle behaviors that reduces risk of developing dementia late in life. However, PA also leads to increased respiration, and in areas with high levels of air pollution, PA may increase exposure to pollutants linked with higher risk of developing dementia. Here, we investigate whether air pollution attenuates the association between PA and dementia risk., Methods: This prospective cohort study included 35,562 adults 60 yrs and older from the UK Biobank. Average acceleration magnitude (ACCave) from wrist-worn accelerometers was used to assess PA levels. Air pollution levels (NO, NO2, PM10, PM2.5, PM2.5-10, and PM2.5 absorbance) were estimated with land use regression methods. Incident all-cause dementia was derived from inpatient hospital records and death registry data., Results: In adjusted models, ACCave was associated with reduced risk of developing dementia (HR = 0.71, 95% confidence interval [CI] = 0.60-0.83), whereas air pollution variables were not associated with dementia risk. There were significant interactions between ACCave and PM2.5 (HRinteraction = 1.33, 95% CI = 1.13-1.57) and PM2.5 absorbance (HRinteraction = 1.24, 95% CI = 1.07-1.45) on incident dementia. At the lowest tertiles of pollution, ACCave was associated with reduced risk of incident dementia (HRPM 2.5 = 0.66, 95% CI = 0.49-0.91; HRPM 2.5 absorbance = 0.60, 95% CI = 0.44-0.81). At the highest tertiles of these pollutants, there was no significant association of ACCave with incident dementia (HRPM 2.5 = 0.88, 95% CI = 0.68-1.14; HRPM 2.5 absorbance = 0.79, 95% CI = 0.60-1.04)., Conclusions: PA is associated with reduced risk of developing all-cause dementia. However, exposure to even moderate levels of air pollution attenuates the benefits of PA on risk of dementia., (Copyright © 2022 by the American College of Sports Medicine.)

Background and Objectives: In high-pollution areas, physical activity may have a paradoxical effect on brain health by increasing particulate deposition in the lungs. We examined whether physical activity modifies associations of air pollution (AP) with brain volumes in an epidemiologic framework., Methods: The UK Biobank enrolled >500,000 adult participants from 2006 to 2010. Wrist accelerometers, multimodal MRI with T1 images and T2 fluid-attenuated inversion recovery data, and land use regression were used to estimate vigorous physical activity (VigPA), structural brain volumes, and AP, respectively, in subsets of the full sample. We evaluated associations among AP interquartile ranges, VigPA, and brain structure volumes and assessed interactions between AP and VigPA., Results: Eight thousand six hundred participants were included, with an average age of 55.55 (SD 7.46) years. After correction for multiple testing, in overall models, VigPA was positively associated with gray matter volume (GMV) and negatively associated with white matter hyperintensity volume (WMHV), while NO 2 , PM 2.5absorbance , and PM 2.5 were negatively associated with GMV. NO 2 and PM 2.5absorbance interacted with VigPA on WMHV (false discovery rate-corrected interaction p = 0.037). Associations between these air pollutants and WMHVs were stronger among participants with high VigPA. Similarly, VigPA was negatively associated with WMHV for those in areas of low NO 2 and PM 2.5absorbance but was null among those living in areas of high NO 2 and PM 2.5absorbance. DISCUSSION: Physical activity is associated with beneficial brain outcomes, while AP is associated with detrimental brain outcomes. VigPA may exacerbate associations of AP with white matter hyperintensity lesions, and AP may attenuate the beneficial associations of physical activity with these lesions., (© 2021 American Academy of Neurology.)

Objective: To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD)., Methods: This is a cross-sectional study of 124 cognitively normal persons aged 64 ± 6 years with a first-degree family history of AD, including 61 APOEε4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [(18)F]-fluorodeoxyglucose-PET rCMRgl measurements., Results: As predicted, higher fasting serum glucose levels were significantly correlated with lower rCMRgl and were confined to the vicinity of brain regions preferentially affected by AD. A similar pattern of regional correlations occurred in the APOEε4 noncarriers and carriers., Conclusions: Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may be associated with AD pathophysiology. Findings suggest that the risk imparted by higher serum glucose levels may be independent of APOEε4 status. This study raises additional questions about the role of the metabolic process in the predisposition to AD and supports the possibility of targeting these processes in presymptomatic AD trials.

Introduction: Apolipoprotein E (ApoE) genotype and aerobic fitness are each associated with cognitive performance in older adults. However, their potentially interactive effects on cognitive performance have not been examined., Purpose: The primary purpose of this study was to determine whether ApoE genotype and aerobic fitness interact to uniquely impact memory performance and executive functioning. A secondary purpose was to examine the interactive effects on other measures of cognition to provide a more comprehensive assessment of cognitive abilities across a broad range of functions., Methods: Community-dwelling, cognitively normal older women (N = 90) provided blood samples to allow for assessment of ApoE genotype, completed cognitive tests, and performed a maximal aerobic fitness test. Primary outcome variables were the auditory verbal learning test (AVLT), the complex figures test (CFT), and the Wisconsin card-sorting task (WCST). Secondary outcome variables were the block design test and the paced auditory serial addition task (PASAT)., Results: Regression analyses indicated that aerobic fitness was associated with significantly better performance on measures of the AVLT, the CFT, and the PASAT for the ApoE-epsilon4 homozygotes., Conclusion: The preliminary findings from this study support the possibility that aerobic fitness is positively associated with the memory performance of those individuals at most genetic risk for Alzheimer disease.

Healthy aging has been associated with brain volume reductions preferentially affecting the frontal cortex, but also involving other regions. We used a network model of regional covariance, the Scaled Subprofile Model, with magnetic resonance imaging voxel-based morphometry to identify the regional distribution of gray matter associated with aging in 26 healthy adults, 22-77 years old. Scaled Subprofile Model analysis identified a pattern that was highly correlated with age (R2=0.66, P

Perioperative pain is still a major problem, and new pharmacological means should be explored to mitigate such pain. Adenosine is an ubiquitous endogenous substance; when exogenously administered, it provides a number of salutary effects including neuromodulation, antinociception, and cytoprotective actions. The aim of this study was to characterize the perioperative antinociceptive-analgesic effects of intraoperative adenosine infusion and determine the duration of actions in the postoperative period, and compare them to those of remifentanil in patients undergoing major surgical procedures in a double-blind study.Sixty-two patients were randomly assigned to one of the two treatments. After standard induction of anesthesia, the lungs were mechanically ventilated. Anesthesia was maintained with a constant alveolar concentration of inhaled anesthetics (3% desflurane and 65% nitrous oxide in oxygen). A variable-rate of intravenous infusion of adenosine (50-500 microg kg(-1) x min(-1)) or remifentanil (0.05-0.5 microg kg(-1) x min(-1)) was initiated 5 min before the skin incision and was titrated to maintain systolic blood pressure and heart rate within 20% of baseline values during surgery. Postoperative evaluations included the level of sedation, degree of pain severity, opioid analgesic (fentanyl, morphine) consumption, and cardiorespiratory variables for 48 h. Intraoperative inhibition of the cardiovascular responses to surgical stimulation could be equally achieved by adenosine or remifentanil, and both could maintain excellent hemodynamic stability. Postoperatively, however, there were striking differences: (1). initial pain score was reduced by 60% (P<0.001) in the adenosine group compared to the remifentanil group and it remained lower throughout the 48 h recovery period; (2). postoperative morphine requirements during the first 0.25, 2 and 48 h were consistently lower in the adenosine group as compared to the remifentanil group (78, 71 and 42%, P<0.001, respectively); (3). adenosine patients remained significantly less sedated at all evaluations; (4) the end-tidal and arterial carbon dioxide values in the remifentanil group were significantly higher when patients were admitted to the postanesthesia care unit. No adverse effect of adenosine was observed at any time. Intraoperative adenosine infusion provided a salutary recovery from anesthesia associated with a pronounced and sustained postoperative pain relief. Compared to remifentanil, adenosine significantly reduced the opioid requirements and minimized the side effects including protracted sedation, cardiorespiratory instability, nausea, and vomiting in the postoperative recovery period.

Objective: (1)H-MRS studies have shown abnormalities in brain levels of myo-inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these abnormalities with dementia severity was not examined. The authors sought to determine whether altered brain levels of mI and other metabolites occur in mild AD and whether they change as dementia severity worsens., Methods: The authors used (1)H-MRS with external standards to measure absolute brain concentrations of mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21 subjects with AD and 17 age- and sex-matched controls in occipital and left and right parietal regions., Results: Concentrations of NAA were significantly decreased, whereas mI and Cr concentrations were significantly increased in all three brain regions in subjects with AD compared with controls. Higher concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of the (1)H-MRS data combined with CSF volume measurements distinguished subjects with AD, ranging from mild to severe dementia, from controls with 100% correct classification. NAA concentration, though not other metabolites, was positively correlated with Mini-Mental State Examination score., Conclusion: The measurements with (1)H-MRS of absolute metabolite concentrations in the neocortex showed abnormal concentrations of brain metabolites in AD; these metabolite concentrations do not necessarily correlate with disease severity. Although changes in myo-inositol and creatine occur in the early stages of AD, abnormalities of N-acetyl aspartate do not occur in mild AD but progressively change with dementia severity. Further, subjects with mild AD can be differentiated from controls with (1)H-MRS.

We sought to investigate how individual differences in the regional patterns of cerebral blood flow (rCBF) relate to task performance during the perceptual matching of faces. We analyzed rCBF data obtained by PET and H2150 from nine young healthy, right-handed, adult males (mean age 29i3 years) using a statistical model of regional covariance, the Scaled Subprofile Model (SSM). SSM analysis performed on a voxel-basis for scan subtractions comparing face-matching and control tasks extracted two patterns whose subject expression in a multiple regression analysis was highly predictive of task accuracy (R2 = 0.87, p < 0.002). The pattern reflecting this linear combination was principally characterized by higher rCBF in regions of bilateral occipital and occipitotemporal cortex, right orbitofrontal cortex, left thalamus, basal ganglia, midbrain, and cerebellum with relatively lower rCBF in anterior cingulate, regions in bilateral prefrontal and temporal cortex, right thalamus, and right inferior parietal cortex. The results indicate that individual subject differences in face matching performance are specifically associated with the functional interaction of cortical and subcortical brain regions previously implicated in aspects of object perception and visual attentional processing.

Objective: To determine whether the size of the corpus callosum is related to the extent of white matter pathology in patients with AD and age-matched healthy control subjects., Methods: White matter hyperintensity load and corpus callosum size were compared between 20 clinically diagnosed AD patients and 21 age-matched healthy control subjects. We investigated the effect of age and disease severity on corpus callosum size and white matter hyperintensity, in addition to the relation between corpus callosum areas and white matter hyperintensity load., Results: We found significant regional atrophy of the corpus callosum in AD when compared with control subjects, although the groups did not differ in their white matter hyperintensity load. We further showed a region-specific correlation between corpus callosum size and white matter hyperintensity in the control group but not in AD patients. In the AD group, corpus callosum size correlated with age and dementia severity, whereas white matter hyperintensity correlated only with age., Conclusion: Corpus callosum atrophy in AD can occur independent of white matter degeneration, likely reflecting specific AD pathology in projecting neurons.

Objective: To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AD) is due entirely to brain atrophy., Background: Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET., Methods: Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects., Results: Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients., Conclusion: Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue.

Background and Purpose: Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n = 27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests., Methods: Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject., Results: The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group x age-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups., Conclusions: Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.

To test the cognitive effects of aging and apolipoprotein E (APOE) in individuals at high risk for Alzheimer's disease (AD), we assessed APOE genotypes and performance on a battery of neuropsychological tests in 41 non-demented, Down syndrome (DS) adults. Old DS subjects (ages 41-61 years) showed poorer memory and orientation scores than young DS adults (ages 22-38 years), but the groups did not differ in other measures after we controlled for intellectual function. Language ability was inversely related to APOE genotype, even after age was controlled for, with the presence of the epsilon 2 allele corresponding to better language skills than epsilon 4. Age-related cognitive changes in non-demented DS adults are consistent with the early effects of AD. The relationship between basic linguistic skills and APOE genotype supports this genetic factor in influencing the development of dementia and AD neuropathology in DS.

To identify changes in brain functions associated with the development of dementia, brain metabolism and cognition were assessed repeatedly in 12 adults with Down syndrome (DS) using positron emission tomography and neuropsychological tests. Ten subjects remained non-demented (ND) and showed no significant changes over time in cognitive measures or in cerebral metabolism. Two subjects developed dementia after 7 years. Brain functions were relatively stable prior to the onset of dementia; after the onset of dementia, both cognitive function and glucose metabolism in parietal and temporal brain regions known to be vulnerable to Alzheimer disease (AD) showed a rapid linear decline. These findings support the concept that brain functions are stable over time in ND individuals with DS and that decline of brain functions in DS subjects with dementia follows two distinct phases that correspond to the clinical progression of AD. This may have implications for timing of new therapeutic strategies.

Spatial attention during visual search was examined in 14 persons with mild Alzheimer's disease (AD) and 28 healthy older subjects, 14 aged 65-74 (young-old), and 14 aged 75-85 (old-old). Subjects searched for single feature (color) or conjunction (color + letter) targets in displays of 10 or 15 letters. Precues of differing sizes were used to provide localizing information of varying precision. Effects of display size and cue size on reaction time (RT) for color search were similar in AD subjects and controls. For color + letter search, however, AD patients showed minimal effects of cue size, pointing to an impairment in AD in the spatial focusing of attention during visual search. Pathology affecting the association parietal and extrastriate areas may mediate impairment of spatial attention and visual search in AD.

We previously reported an inverse relation between parietal cerebral blood flow and years of education in Alzheimer's disease (AD) patients matched for clinical severity. This suggested that the clinical manifestation of advancing AD pathology is delayed in patients with higher educational attainment. Other aspects of life experience may also provide a reserve against the clinical expression of AD. To test this hypothesis, we classified the primary life-time occupations of 51 AD patients using the Dictionary of Occupational Titles, published by the US Department of Labor, and derived six factor scores describing intellectual, interpersonal, and physical job demands. Regional cerebral blood flow was measured using the xenon-133 inhalation method. After controlling for age, clinical dementia severity, and education, there was less relative perfusion in the parietal region in subjects whose occupations were associated with higher interpersonal skills and physical demands factor scores. We conclude that independent of education, aspects of occupational experience may provide a reserve that delays the clinical manifestation of AD.

The motor circuitry of the basal ganglia is organized in parallel with basal ganglia circuits involved in oculomotor, associative, and limbic functions. These circuits comprise reentrant pathways that originate in various neocortical domains and pass through the basal ganglia before returning, by way of the thalamus, to select portions of the frontal lobe. Recent progress in characterizing the anatomy and physiology of these pathways has provided new insights into the pathophysiology of basal ganglia-related movement disorders and enhanced our understanding of the normal role of the basal ganglia in movement control and adaptive motor behavior.

The clinical features and CSF characteristics of five patients with primary Sjögren's syndrome (SS) and associated aseptic meningoencephalitis (AME) are described. Episodes of AME were recurrent in four patients. Viral, fungal, and bacterial cultures were uniformly negative. Plasma cells were observed in the CSF but not in the blood of three patients. The CSF IgG:albumin index was elevated, suggesting intrathecal synthesis of IgG in each of the four patients tested; each patient had either one or two broad bands with the mobility of IgG on CSF agarose electrophoresis. These observations are consistent with current understanding of SS as a polyclonal gammopathy associated with the multifocal proliferation of B lymphocytes and plasma cells.

Although peripheral nervous system disease has been well documented in Sjögren's syndrome (SS), central nervous system (CNS) involvement is considered distinctly uncommon. Sixteen patients with primary SS and CNS disorders not attributable to other causes were the subjects of this study. Cerebral manifestations, both focal and diffuse, as well as spinal cord disease, were observed. Peripheral vasculitis occurred in 12 patients (75%), 83% of whom had anti-Ro(SSA) antibodies. The high proportion of patients with concomitant peripheral vasculitis, and the observed association with antibodies to the Ro(SSA) antigen system which, in other studies, has been linked to vasculitis in SS, suggest that an immune vasculopathy may play a role in the pathogenesis of the CNS disease of SS.

We studied eight patients who had primary Sjögren syndrome and central nervous system (CNS) disorders that were not attributable to other causes. Focal cerebral deficits were observed in five patients. Aseptic meningoencephalitis was seen in five patients, recurrent in one. Spinal cord manifestations in three patients took several forms: acute transverse myelitis, chronic progressive myelopathy, and spinal subarachnoid hemorrhage. Precipitating antibodies to the Ro(SSA) cytoplasmic antigen were detected in the sera of seven of eight patients. This may be relevant to the pathogenesis of CNS disease in Sjögren syndrome, because there is a strong correlation between vasculitis and the presence of anti-Ro(SSA) antibodies in this connective tissue disorder.