Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years.

The present study sought to determine whether supplementation of long-chain polyunsaturated fatty acids (LCPUFA) during the first year of life influenced brain function, structure, and metabolism at 9 years of age. Newborns were randomly assigned to consume formula containing either no LCPUFA (control) or formula with 0.64% of total fatty acids as arachidonic acid (ARA; 20:4n6) and variable amounts of docosahexaenoic acid (DHA; 22:6n3) (0.32%, 0.64%, or 0.96% of total fatty acids) from birth to 12 months. At age 9 years (±0.6), 42 children enrolled in a follow-up multimodal magnetic resonance imaging (MRI) study including functional (fMRI, Flanker task), resting state (rsMRI), anatomic, and proton magnetic resonance spectroscopy (1 H MRS). fMRI analysis using the Flanker task found that trials requiring greater inhibition elicited greater brain activation in LCPUFA-supplemented children in anterior cingulate cortex (ACC) and parietal regions. rsMRI analysis showed that children in the 0.64% group exhibited greater connectivity between prefrontal and parietal regions compared to all other groups. In addition, voxel-based analysis (VBM) revealed that the 0.32% and 0.64% groups had greater white matter volume in ACC and parietal regions compared to controls and the 0.96% group. Finally, 1 H MRS data analysis identified that N-acetylaspartate (NAA) and myo-inositol (mI) were higher in LCPUFA groups compared to the control group. LCPUFA supplementation during infancy has lasting effects on brain structure, function, and neurochemical concentrations in regions associated with attention (parietal) and inhibition (ACC), as well as neurochemicals associated with neuronal integrity (NAA) and brain cell signaling (mI).

Cognitive Function and White Matter Changes Associated with Renal Transplantation.

BACKGROUND: End-stage renal disease (ESRD) is a disease with an aging population and a high prevalence of cognitive impairment affecting quality of life, health care costs and mortality. Structural changes in the brain with decreased white matter integrity have been observed in ESRD. Understanding the changes in cognition and associated changes in brain structure after renal transplantation can help define the mechanisms underlying cognitive impairment in ESRD. METHODS: We conducted a prospective, observational cohort study in ESRD patients listed for renal transplantation and followed them post-transplantation. We assessed their cognitive function with a battery of neuropsychological tests and brain white matter integrity with diffusion tensor imaging (DTI) both before transplant and 3 months after transplant. RESULTS: Eleven patients, aged 56.5 ± 10.7 years, completed the study. Cognitive measures of memory and executive function improved after the transplant, specifically on tests of logical memory I (p = 0.004), logical memory II (p = 0.003) and digit symbol (p < 0.0001). DTI metrics also improved post the transplant with an increase in fractional anisotropy (p = 0.01) and decrease in mean diffusivity (p = 0.004). These changes were more prominent in tracts associated with memory and executive function. CONCLUSIONS: Cognitive function, particularly memory and executive function, improve post the transplant with concurrent improvements in white matter integrity in tracts associated with memory and executive function. These data suggest that abnormalities in cognition and brain structure seen in the ESRD population are at least partially reversible.

Is Alzheimer's disease a systemic disease?

Although Alzheimer's disease (AD) is the most common neurodegenerative disease, the etiology of AD is not well understood. In some cases, genetic factors explain AD risk, but a high percentage of late-onset AD is unexplained. The fact that AD is associated with a number of physical and systemic manifestations suggests that AD is a multifactorial disease that affects both the CNS and periphery. Interestingly, a common feature of many systemic processes linked to AD is involvement in energy metabolism. The goals of this review are to 1) explore the evidence that peripheral processes contribute to AD risk, 2) explore ways that AD modulates whole-body changes, and 3) discuss the role of genetics, mitochondria, and vascular mechanisms as underlying factors that could mediate both central and peripheral manifestations of AD. Despite efforts to strictly define AD as a homogeneous CNS disease, there may be no single etiologic pathway leading to the syndrome of AD dementia. Rather, the neurodegenerative process may involve some degree of baseline genetic risk that is modified by external risk factors. Continued research into the diverse but related processes linked to AD risk is necessary for successful development of disease-modifying therapies.

Insulin is differentially related to cognitive decline and atrophy in Alzheimer's disease and aging.

We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over two years in early Alzheimer's disease (AD, n=48) and nondemented controls (n=61). Intravenous glucose tolerance tests were conducted at baseline to determine insulin area-under-the-curve (AUC). A standard battery of cognitive tasks and MRI were conducted at baseline and 2-year follow-up. In nondemented controls, higher baseline insulin AUC was associated with 2-year decline in global cognitive performance (beta=-0.36, p=0.005). In early AD, however, higher insulin AUC was associated with less decline in global cognitive performance (beta=0.26, p=0.06), slower global brain atrophy (beta=0.40, p=0.01) and less regional atrophy in the bilateral hippocampi and cingulate cortices. While insulin resistance is associated with cognitive decline in nondemented aging, higher peripheral insulin may have AD-specific benefits or insulin signaling may be affected by systemic physiologic changes associated with AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Increased Functional Connectivity of the Precuneus in Individuals with a Family History of Alzheimer's Disease.

BACKGROUND: First-degree relatives of individuals with late-onset Alzheimer's disease (AD) have increased risk for AD, with children of affected parents at an especially high risk. OBJECTIVE: We aimed to investigate default mode network connectivity, medial temporal cortex volume, and cognition in cognitively healthy (CH) individuals with (FH+) and without (FH-) a family history of AD, alongside amnestic mild cognitive impairment (aMCI) and AD individuals, to determine the context and directionality of dysfunction in at-risk individuals. Our primary hypothesis was that there would be a linear decline (CH FH- > CH FH+ > aMCI > AD) within the risk groups on all measures of AD risk. METHODS: We used MRI and fMRI to study cognitively healthy individuals (n = 28) with and without AD family history (FH+ and FH-, respectively), those with aMCI (n = 31) and early-stage AD (n = 25). We tested connectivity within the default mode network, as well as measures of volume and thickness within the medial temporal cortex and selected seed regions. RESULTS: As expected, we identified decreased medial temporal cortex volumes in the aMCI and AD groups compared to cognitively healthy groups. We also observed patterns of connectivity across risk groups that suggest a nonlinear relationship of change, such that the FH+ group showed increased connectivity compared to the FH- and AD groups (CH FH+ > CH FH- > aMCI > AD). This pattern emerged primarily in connectivity between the precuneus and frontal regions. CONCLUSION: These results add to a growing literature that suggests compensatory brain function in otherwise cognitively healthy individuals with a family history of AD.

Alzheimer's disease cortical morphological phenotypes are associated with TOMM40'523-APOE haplotypes.

Both the APOE ε4 and TOMM40 rs10524523 ("523") genes have been associated with risk for Alzheimer's disease (AD) and neuroimaging biomarkers of AD. No studies have investigated the relationship of TOMM40'523-APOE ε4 on the structural complexity of the brain in AD individuals. We quantified brain morphology and multiple cortical attributes in individuals with mild cognitive impairment (MCI) and AD, then tested whether APOE ε4 or TOMM40 poly-T genotypes were related to AD morphological biomarkers in cognitively unimpaired (CU) and MCI/AD individuals. We identified several AD-specific phenotypes in brain morphology and found that TOMM40 poly-T short alleles are associated with early, AD-specific brain morphological differences in healthy aging. We observed decreased cortical thickness, sulcal depth, and fractal dimension in CU individuals with the poly-T short alleles. Moreover, in MCI/AD participants, the APOE ε4 (TOMM40 L) individuals had a higher rate of gene-related morphological markers indicative of AD. Our data suggest that TOMM40'523 is associated with early brain structure variations in the precuneus, temporal, and limbic cortices.

Evidence of altered corticomotor system connectivity in early-stage Alzheimer's disease.

BACKGROUND AND PURPOSE: There is increasing evidence for subtle motor dysfunction early in Alzheimer disease (AD), including common motor behaviors that were once considered unaffected early in the disease process. Our objective was to assess whether functional neural networks underlying motor behavior are altered by AD. METHODS: We investigated AD-related differences in regional brain activation during motor performance. Nine older adults with early-stage AD and 10 without dementia underwent functional magnetic resonance imaging while performing a visually directed simple motor task (hand squeeze). RESULTS: Despite some similarity in brain activation during motor performance, we found that individuals without dementia exhibited greater activation in accessory motor regions, supplementary motor area, and cerebellum compared with those with AD. We also assessed disease-related differences in regions where activity was functionally integrated with primary motor cortex. Using a psychophysiological interaction analysis, we found that those with AD displayed increased coactivation with primary motor cortex of bilateral motor and visual regions. DISCUSSION AND CONCLUSIONS: These AD-related differences in regional coactivation during motor execution may represent inefficiency in the motor network as a consequence of the disease process. Alternatively, they may represent compensatory activation. These findings provide further evidence that in early stages of AD, neuromotor function is altered even during simple motor behaviors. The results may have implications for performance of more complex tasks and may be associated with the well-characterized decline in dual-task performance in those with AD.

The neuroanatomy of genetic subtype differences in Prader-Willi syndrome.

Despite behavioral differences between genetic subtypes of Prader-Willi syndrome (PWS), no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of PWS [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Fifteen individuals with PWS due to a typical deletion [(DEL) type I; n = 5, type II; n = 10], eight with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume (WMV) between groups, covarying for age, sex, and body mass index (BMI). Overall, compared to HWC, PWS individuals had lower gray matter volumes (GMV) that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower WMVs in the brain stem, cerebellum, medial temporal, and frontal cortex. Compared to UPD, the DEL subtypes had lower GMV primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and WMVs in the orbitofrontal and limbic cortices compared to HWC. These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes.

Cerebrovascular response to exercise interacts with individual genotype and amyloid-beta deposition to influence response inhibition with aging.

The etiology of cognitive dysfunction associated with Alzheimer's disease (AD) and dementia is multifactorial. Yet, mechanistic interactions among key neurobiological factors linked to AD pathology are unclear. This study tested the effect of interactions between cerebrovascular function, individual genotype, and structural brain pathology on response inhibition performance, an early and sensitive indicator of cognitive executive dysfunction with aging. We quantified cerebrovascular response (CVR) to moderate-intensity aerobic exercise using transcranial doppler ultrasound and global amyloid-beta (Aß) deposition using positron emission tomography in a group of cognitively normal older adults genotyped as APOE4 carriers and noncarriers. We quantified response inhibition during a cognitive Stroop test. Individuals with blunted CVR possessed greater Aß deposition. There was CVR-by-carrier status-by-Aß interaction on response inhibition. Blunted CVR was associated with impaired response inhibition specifically in APOE4 carriers. Despite having greater Aß deposition, APOE4 carriers with higher CVR demonstrated better response inhibition. Cerebrovascular interactions with individual genotype and structural brain pathology may provide a physiologically-informed target for precision-medicine approaches for early treatment and prevention of cognitive dysfunction with aging.

Sex Differences in Resilience and Resistance to Brain Pathology and Dysfunction Moderated by Cerebrovascular Response to Exercise and Genetic Risk for Alzheimer's Disease.

Sex as a biological variable appears to contribute to the multifactorial etiology of Alzheimer's disease. We tested sex-based interactions between cerebrovascular function and APOE4 genotype on resistance and resilience to brain pathology and cognitive executive dysfunction in cognitively-normal older adults. Female APOE4 carriers had higher amyloid-ß deposition yet achieved similar cognitive performance to males and female noncarriers. Further, female APOE4 carriers with robust cerebrovascular responses to exercise possessed lower amyloid-ß. These results suggest a unique cognitive resilience and identify cerebrovascular function as a key mechanism for resistance to age-related brain pathology in females with high genetic vulnerability to Alzheimer's disease.

Dementia risk and dynamic response to exercise: A non-randomized clinical trial.

BACKGROUND: Physical exercise may support brain health and cognition over the course of typical aging. The goal of this nonrandomized clinical trial was to examine the effect of an acute bout of aerobic exercise on brain blood flow and blood neurotrophic factors associated with exercise response and brain function in older adults with and without possession of the Apolipoprotein epsilon 4 (APOE4) allele, a genetic risk factor for developing Alzheimer's. We hypothesized that older adult APOE4 carriers would have lower cerebral blood flow regulation and would demonstrate blunted neurotrophic response to exercise compared to noncarriers. METHODS: Sixty-two older adults (73±5 years old, 41 female [67%]) consented to this prospectively enrolling clinical trial, utilizing a single arm, single visit, experimental design, with post-hoc assessment of difference in outcomes based on APOE4 carriership. All participants completed a single 15-minute bout of moderate-intensity aerobic exercise. The primary outcome measure was change in cortical gray matter cerebral blood flow in cortical gray matter measured by magnetic resonance imaging (MRI) arterial spin labeling (ASL), defined as the total perfusion (area under the curve, AUC) following exercise. Secondary outcomes were changes in blood neurotrophin concentrations of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and brain derived neurotrophic factor (BDNF). RESULTS: Genotyping failed in one individual (n = 23 APOE4 carriers and n = 38 APOE4 non-carriers) and two participants could not complete primary outcome testing. Cerebral blood flow AUC increased immediately following exercise, regardless of APOE4 carrier status. In an exploratory regional analyses, we found that cerebral blood flow increased in hippocampal brain regions, while showing no change in cerebellum across both groups. Among high inter-individual variability, there were no significant changes in any of the 3 neurotrophic factors for either group immediately following exercise. CONCLUSIONS: Our findings show that both APOE4 carriers and non-carriers show similar effects of exercise-induced increases in cerebral blood flow and neurotrophic response to acute aerobic exercise. Our results provide further evidence that acute exercise-induced increases in cerebral blood flow may be regional specific, and that exercise-induced neurotrophin release may show a differential effect in the aging cardiovascular system. Results from this study provide an initial characterization of the acute brain blood flow and neurotrophin responses to a bout of exercise in older adults with and without this known risk allele for cardiovascular disease and Alzheimer's disease. TRIAL REGISTRATION: Dementia Risk and Dynamic Response to Exercise (DYNAMIC); Identifier: NCT04009629.

Relationship of fasting glucose and longitudinal Alzheimer's disease imaging markers.

INTRODUCTION: Fasting glucose increases with age and is linked to modifiable Alzheimer's disease risk factors such as cardiovascular disease and Type 2 diabetes (T2D). METHODS: We leveraged available biospecimens and neuroimaging measures collected during the Alzheimer's Prevention Through Exercise (APEx) trial (n = 105) to examine the longitudinal relationship between change in blood glucose metabolism and change in regional cerebral amyloid deposition and gray and white matter (WM) neurodegeneration in older adults over 1 year of follow-up. RESULTS: Individuals with improving fasting glucose (n = 61) exhibited less atrophy and regional amyloid accumulation compared to those whose fasting glucose worsened over 1 year (n = 44). Specifically, while individuals with increasing fasting glucose did not yet show cognitive decline, they did have regional atrophy in the hippocampus and inferior parietal cortex, and increased amyloid accumulation in the precuneus cortex. Signs of early dementia pathology occurred in the absence of significant group differences in insulin or body composition, and was not modified by apolipoprotein E ε4 carrier status. DISCUSSION: Dysregulation of glucose in late life may signal preclinical brain change prior to clinically relevant cognitive decline. Additional work is needed to determine whether treatments specifically targeting fasting glucose levels may impact change in brain structure or cerebral amyloid in older adults.

Role of lean body mass in estimating glomerular filtration rate in Alzheimer disease.

BACKGROUND: The association between estimated glomerular filtration rate (eGFR) and progression of Alzheimer disease (AD), as measured by cognitive decline and brain atrophy, has been infrequently studied. Since AD is characterized by sarcopenia and other changes in body composition, which are known to influence GFR, a determination of how lean mass (LM) affects estimation of GFR in AD patients is important. METHODS: Participants were drawn from a prospective longitudinal study of brain ageing and AD in community-dwelling individuals. Control (n = 60) and AD (n = 61) participants were enrolled. Estimated GFR was calculated using the four-variable Modification of Diet in Renal Disease (MDRD), Cockroft-Gault, Macdonald appendicular LM and Taylor LM equations. Association of eGFR with 2-year change in cognitive function and brain volume was assessed. RESULTS: Individuals with AD demonstrated a paradoxical finding in which lower baseline MDRD eGFR was associated with less cognitive decline (P = 0.04) and brain atrophy (P = 0.02), a phenomenon not observed in non-AD controls. This finding was abolished in the AD patients when either the Macdonald appendicular LM or Taylor LM equations were used. While significant group-by-eGFR interactions were present for cognitive decline (P = 0.006) and brain atrophy (P = 0.001) when the MDRD equation was used, no group-by-eGFR interactions were present when either the Macdonald LM (P = 0.58 and P = 0.10 for cognitive decline and brain atrophy, respectively) or Taylor LM (P = 0.97 and P = 0.55) equations were used. CONCLUSIONS: Accounting for measures of LM in GFR estimation appears to significantly mitigate counterintuitive relationships between measures of AD progression and eGFR as calculated by more traditional measures of renal function. This suggests that consideration of LM in eGFR calculations may be important in patients with sarcopenia, such as the AD population.

Cardiorespiratory response to exercise testing in individuals with Alzheimer's disease.

OBJECTIVE: To examine exercise testing response in Alzheimer's disease (AD) and possible disease-related change over time. DESIGN: Retrospective assessment of a 2-year observational study. SETTING: University medical center. PARTICIPANTS: Individuals without dementia (n=50) and with AD (n=31). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants underwent a clinical dementia evaluation and performed an incremental exercise test using a treadmill and the modified Bruce protocol at baseline and at a 2-year follow-up. We examined oxygen consumption, minute ventilation, heart rate, and ventilatory equivalents for oxygen and carbon dioxide at submaximal and peak exercise intensities to determine whether the measures were different between groups or over time. RESULTS: Participants with AD and those without dementia performed similarly at submaximal effort, and both groups showed similar changes in exercise response over 2 years. However, nondemented individuals had consistently higher values of oxygen consumption (P≤.02) and minute ventilation at peak effort at baseline (P=.003). CONCLUSIONS: Individuals with AD demonstrate physiologic responses to submaximal exercise effort that are not significantly different than individuals without dementia. However, differences are apparent at the extreme of effort.

High Glycemic Diet Is Related to Brain Amyloid Accumulation Over One Year in Preclinical Alzheimer's Disease.

Objective: To test the hypothesis that high glycemic diet is related to 1-year change in brain amyloid based on our prior cross-sectional evidence that high glycemic diet is associated with brain amyloid. Methods: This longitudinal, observational study assessed the relationship between reported habitual consumption of a high glycemic diet (HGDiet) pattern and 1-year brain amyloid change measured by Florbetapir F18 PET scans in 102 cognitively normal older adults with elevated or sub-threshold amyloid status that participated in a 1-year randomized, controlled exercise trial at the University of Kansas Medical Center in Kansas City. Results: Among all participants (n = 102), higher daily intake of the HGDiet pattern (ß = 0.06, p = 0.04), sugar (ß = 0.07, p = 0.01), and total carbohydrate (ß = 0.06, p = 0.04) were related to more precuneal amyloid accumulation. These relationships in the precuneus were accentuated in participants with elevated amyloid at enrollment (n = 70) where higher intake of the HGDiet pattern, sugar, and carbohydrate were related to more precuneal amyloid accumulation (ß = 0.11, p = 0.01 for all measures). In individuals with elevated amyloid, higher intake of the HGDiet pattern was also related to more amyloid accumulation in the lateral temporal lobe (ß = 0.09, p < 0.05) and posterior cingulate gyrus (ß = 0.09, p < 0.05) and higher sugar and carbohydrate intake were also related to more amyloid accumulation in the posterior cingulate gyrus (ß = 0.10, p < 0.05 for both measures). Conclusion: This longitudinal observational analysis suggests that a high glycemic diet relates to higher brain amyloid accumulation over 1 year in regions of the temporoparietal cortex in cognitively normal adults, particularly in those with elevated amyloid status. Further studies are required to assess whether there is causal link between a high glycemic diet and brain amyloid. Clinical Trial Registration: ClinicalTrials.gov, Identifier (NCT02000583).

Aerobic exercise improves hippocampal blood flow for hypertensive Apolipoprotein E4 carriers.

Cerebrovascular dysfunction likely contributes causally to Alzheimer's disease (AD). The strongest genetic risk factor for late-onset AD, Apolipoprotein E4 (APOE4), may act synergistically with vascular risk to cause dementia. Therefore, interventions that improve vascular health, such as exercise, may be particularly beneficial for APOE4 carriers. We assigned cognitively normal adults (65-87 years) to an aerobic exercise intervention or education only. Arterial spin labeling MRI measured hippocampal blood flow (HBF) before and after the 52-week intervention. We selected participants with hypertension at enrollment (n = 44). For APOE4 carriers, change in HBF (ΔHBF) was significantly (p = 0.006) higher for participants in the exercise intervention (4.09 mL/100g/min) than the control group (-2.08 mL/100g/min). There was no difference in ΔHBF between the control (-0.32 mL/100g/min) and exercise (-0.54 mL/100g/min) groups for non-carriers (p = 0.918). Additionally, a multiple regression showed an interaction between change in systolic blood pressure (ΔSBP) and APOE4 carrier status on ΔHBF (p = 0.035), with reductions in SBP increasing HBF for APOE4 carriers only. Aerobic exercise improved HBF for hypertensive APOE4 carriers only. Additionally, only APOE4 carriers exhibited an inverse relationship between ΔSBP and ΔHBF. This suggests exercise interventions, particularly those that lower SBP, may be beneficial for individuals at highest genetic risk of AD.ClinicalTrials.gov Identifier: NCT02000583.

Rationale and methods to characterize the acute exercise response in aging and Alzheimer's Disease: the AEROBIC pilot study.

There is evidence that exercise benefits the brain, but the mechanisms for this benefit are unclear. The chronic benefits of exercise are likely a product of discreet, acute responses in exercise-related blood biomarkers and brain metabolism. This acute exercise response has not been compared in aging and Alzheimer's Disease (AD). It is known that acute exercise elicits a powerful peripheral response in young individuals, and exercise-related biomarkers such as glucose and lactate readily penetrate the brain. How this changes with aging and neurodegenerative disease is less clear. It is critical to characterize and understand the acute effects of exercise, including different exercise intensities, in terms of the peripheral metabolic response and relationship with brain metabolism. This will help determine potential mechanisms for brain benefits of exercise and better inform the design of future clinical trials. The primary goal of the AEROBIC study is to characterize the acute exercise response of brain glucose metabolism and exercise-related blood biomarkers. We will measure how cerebral metabolism is affected by an acute bout of moderate and higher intensity exercise and characterize the extent to which this differs between cognitively healthy older adults and individuals with AD. Related to this primary goal, we will quantify the peripheral biomarker response to moderate and higher intensity exercise and how this relates to brain metabolic change in both groups.

Head positioning and risk of pneumocephalus, air embolism, and hemorrhage during subthalamic deep brain stimulation surgery.

PURPOSE: The objective of the present study was to evaluate the risk of pneumocephalus, venous air embolism (VAE), and intracranial hemorrhage in subthalamic nucleus (STN) deep brain stimulation (DBS) patients operated in the strict supine (head and body flat) position. METHODS: This was a retrospective review of clinical records and brain imaging of patients who underwent STN DBS between January 2007 and June 2009 at the University of Kansas Medical Center. RESULTS: A total of 61 patients underwent 114 lead implantations (53 staged bilateral and 8 unilateral). No case involved a transventricular route. Intracranial air volumes ranged from 0 to 7.02 cm³ (mean 0.98 ± 1.42 cm³). Pneumocephalus volumes were highly skewed with no air present after 44 (38.6%) lead implantations, >0 to 1 cm³ in 35 (30.7%), >2 to 3 cm³ in 17 (14.9%), and >3 cm³ (average 4.97 cm³) in 9 (7.9%). There was no incidence of clinically apparent VAE or symptomatic intracranial hemorrhage. There was no association between age, degree of atrophy, sagittal angle of surgical approach, number of microelectrode runs (MERs), distance of gyrus from inner skull bone at the entry point, or surgical side and pneumocephalus. However, the majority of lead implantations (100 leads; 88%) required only one MER and there were minimal measurable distances between entered gyrus and adjacent bone. CONCLUSIONS: Our data suggest that strict supine positioning during STN DBS surgery results in minimal intracranial air and is not associated with VAE or symptomatic intracranial hemorrhage when the operative method described is used.

Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer's Disease.

BACKGROUND: Individuals with Alzheimer's Disease (AD) are often characterized by systemic markers of insulin resistance; however, the broader effects of AD on other relevant metabolic hormones, such as incretins that affect insulin secretion and food intake, remains less clear. METHODS: Here, we leveraged a physiologically relevant meal tolerance test to assess diagnostic differences in these metabolic responses in cognitively healthy older adults (CH; n = 32) and AD (n = 23) participants. All individuals also underwent a comprehensive clinical examination, cognitive evaluation, and structural magnetic resonance imaging. RESULTS: The meal-stimulated response of glucose, insulin, and peptide tyrosine tyrosine (PYY) was significantly greater in individuals with AD as compared to CH. Voxel-based morphometry revealed negative relationships between brain volume and the meal-stimulated response of insulin, C-Peptide, and glucose-dependent insulinotropic polypeptide (GIP) in primarily parietal brain regions. CONCLUSION: Our findings are consistent with prior work that shows differences in metabolic regulation in AD and relationships with cognition and brain structure.

Cardiorespiratory fitness and preserved medial temporal lobe volume in Alzheimer disease.

Exercise and cardiorespiratory (CR) fitness may moderate age-related regional brain changes in nondemented (ND) older adults. The relationship of fitness to Alzheimer disease (AD)-related brain change is understudied, particularly in the hippocampus, which is disproportionately affected in early AD. The role of apolipoprotein E4 (apoE4) genotype in modulating this relationship is also unknown. ND (n=56) and early-stage AD patients (n=61) over the age of 65 years had magnetic resonance imaging and CR fitness assessments. Voxel-based morphometry techniques were used to identify AD-related atrophy. We analyzed the relationship of CR fitness with white and gray matter within groups, assessed fitness-related brain volume change in areas most affected by AD-related atrophy, and then analyzed differential fitness-brain relationships between apoE4 carriers. Atrophy was present in the medial temporal, temporal, and parietal cortices in patients with mild AD. There was a significant positive correlation of CR fitness with parietal and medial temporal volume in AD patients. ND patients did not have a significant relationship between brain volume and CR fitness in the global or small volume correction analyses. There was not a significant interaction for fitness x apoE4 genotype in either group. In early-stage AD, CR fitness is associated with regional brain volumes in the medial-temporal and parietal cortices suggesting that maintaining CR fitness may modify AD-related brain atrophy.