Physical Effort Exertion for Peer Feedback Reveals Evolving Social Motivations From Adolescence to Young Adulthood.

Peer relationships and social belonging are particularly important during adolescence. Using a willingness-to-work paradigm to quantify incentive motivation, we examined whether evaluative information holds unique value for adolescents. Participants (N = 102; 12-23 years old) rated peers, predicted how peers rated them, and exerted physical effort to view each peer's rating. We measured grip force, speed, and opt-out behavior to examine the motivational value of peer feedback, relative to money in a control condition, and to assess how peer desirability and participants' expectations modulated motivated effort across age. Overall, when compared with adolescents, adults were relatively less motivated for feedback than money. Whereas adults exerted less force and speed for feedback when expecting rejection, adolescents exerted greater force and speed when expecting to be more strongly liked or disliked. These findings suggest that the transition into adulthood is accompanied by a self-protective focus, whereas adolescents are motivated to consume highly informative feedback, even if negative.

The Lifespan Human Connectome Project in Development: A large-scale study of brain connectivity development in 5-21 year olds.

Recent technological and analytical progress in brain imaging has enabled the examination of brain organization and connectivity at unprecedented levels of detail. The Human Connectome Project in Development (HCP-D) is exploiting these tools to chart developmental changes in brain connectivity. When complete, the HCP-D will comprise approximately ∼1750 open access datasets from 1300 + healthy human participants, ages 5-21 years, acquired at four sites across the USA. The participants are from diverse geographical, ethnic, and socioeconomic backgrounds. While most participants are tested once, others take part in a three-wave longitudinal component focused on the pubertal period (ages 9-17 years). Brain imaging sessions are acquired on a 3 T Siemens Prisma platform and include structural, functional (resting state and task-based), diffusion, and perfusion imaging, physiological monitoring, and a battery of cognitive tasks and self-reports. For minors, parents additionally complete a battery of instruments to characterize cognitive and emotional development, and environmental variables relevant to development. Participants provide biological samples of blood, saliva, and hair, enabling assays of pubertal hormones, health markers, and banked DNA samples. This paper outlines the overarching aims of the project, the approach taken to acquire maximally informative data while minimizing participant burden, preliminary analyses, and discussion of the intended uses and limitations of the dataset.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using magnetic resonance imaging, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n=24, 13 males, 11 females) and standard (n=17, 8 males, 9 females) diets. Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A Diet X Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24; 13 males, 11 females) and standard diets (n = 17; 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A diet x age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

Rhesus macaque brain morphometry: a methodological comparison of voxel-wise approaches.

Voxel-based morphometry studies have become increasingly common in human neuroimaging over the past several years; however, few studies have utilized this method to study morphometry changes in non-human primates. Here we describe the application of voxel-wise morphometry methods to the rhesus macaque (Macaca mulatta) using the 112RM-SL template and priors (McLaren et al. (2009) [42]) and as an illustrative example we describe age-associated changes in grey matter morphometry. Specifically, we evaluated the unified segmentation routine implemented using Statistical Parametric Mapping (SPM) software and the FMRIB's Automated Segmentation Tool (FAST) in the FMRIB Software Library (FSL); the effect of varying the smoothing kernel; and the effect of the normalization routine. We found that when studying non-human primates, brain images need less smoothing than in human studies, 2-4mm FWHM. Using flow field deformations (DARTEL) improved inter-subject alignment leading to results that were more likely due to morphometry differences as opposed to registration differences.

How adolescents and adults translate motivational value to action: Age-related shifts in strategic physical effort exertion for monetary rewards.

Adults titrate the degree of physical effort they are willing to expend according to the magnitude of reward they expect to obtain, a process guided by incentive motivation. However, it remains unclear whether adolescents, who are undergoing normative developmental changes in cognitive and reward processing, translate incentive motivation into action in a way that is similarly tuned to reward value and economical in effort utilization. The present study adapted a classic physical effort paradigm to quantify age-related changes in motivation-based and strategic markers of effort exertion for monetary rewards from adolescence to early adulthood. One hundred three participants aged 12-23 years completed a task that involved exerting low or high amounts of physical effort, in the form of a hand grip, to earn low or high amounts of money. Adolescents and young adults exhibited highly similar incentive-modulated effort for reward according to measures of peak grip force and speed, suggesting that motivation for monetary reward is consistent across age. However, young adults expended energy more economically and strategically: Whereas adolescents were prone to exert excess physical effort beyond what was required to earn reward, young adults were more likely to strategically prepare before each grip phase and conserve energy by opting out of low reward trials. This work extends theoretical models of development of incentive-driven behavior by demonstrating that layered on similarity in motivational value for monetary reward, there are important differences in the way behavior is flexibly adjusted in the presence of reward from adolescence to young adulthood. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Increase in Suicidal Thinking During COVID-19.

There is concern that the COVID-19 pandemic may cause increased risk of suicide. In the current study, we tested whether suicidal thinking has increased during the COVID-19 pandemic and whether such thinking was predicted by increased feelings of social isolation. In a sample of 55 individuals recently hospitalized for suicidal thinking or behaviors and participating in a 6-month intensive longitudinal smartphone monitoring study, we examined suicidal thinking and isolation before and after the COVID-19 pandemic was declared a national emergency in the United States. We found that suicidal thinking increased significantly among adults (odds ratio [OR] = 4.01, 95% confidence interval [CI] = [3.28, 4.90], p < .001) but not adolescents (OR = 0.84, 95% CI = [0.69, 1.01], p = .07) during the onset of the COVID-19 pandemic. Increased feelings of isolation predicted suicidal thinking during the pandemic phase. Given the importance of social distancing policies, these findings support the need for digital outreach and treatment.

Strain-Level Diversity Impacts Cheese Rind Microbiome Assembly and Function.

Diversification can generate genomic and phenotypic strain-level diversity within microbial species. This microdiversity is widely recognized in populations, but the community-level consequences of microbial strain-level diversity are poorly characterized. Using the cheese rind model system, we tested whether strain diversity across microbiomes from distinct geographic regions impacts assembly dynamics and functional outputs. We first isolated the same three bacterial species (Staphylococcus equorum, Brevibacterium auranticum, and Brachybacterium alimentarium) from nine cheeses produced in different regions of the United States and Europe to construct nine synthetic microbial communities consisting of distinct strains of the same three bacterial species. Comparative genomics identified distinct phylogenetic clusters and significant variation in genome content across the nine synthetic communities. When we assembled each synthetic community with initially identical compositions, community structure diverged over time, resulting in communities with different dominant taxa. The taxonomically identical communities showed differing responses to abiotic (high salt) and biotic (the fungus Penicillium) perturbations, with some communities showing no response and others substantially shifting in composition. Functional differences were also observed across the nine communities, with significant variation in pigment production (light yellow to orange) and in composition of volatile organic compound profiles emitted from the rinds (nutty to sulfury).IMPORTANCE Our work demonstrated that the specific microbial strains used to construct a microbiome could impact the species composition, perturbation responses, and functional outputs of that system. These findings suggest that 16S rRNA gene taxonomic profiles alone may have limited potential to predict the dynamics of microbial communities because they usually do not capture strain-level diversity. Observations from our synthetic communities also suggest that strain-level diversity has the potential to drive variability in the aesthetics and quality of surface-ripened cheeses.

Rapid Phenotypic and Metabolomic Domestication of Wild Penicillium Molds on Cheese.

Fermented foods provide novel ecological opportunities for natural populations of microbes to evolve through successive recolonization of resource-rich substrates. Comparative genomic data have reconstructed the evolutionary histories of microbes adapted to food environments, but experimental studies directly demonstrating the process of domestication are lacking for most fermented food microbes. Here, we show that during adaptation to cheese, phenotypic and metabolomic traits of wild Penicillium molds rapidly change to produce domesticated phenotypes with properties similar to those of the industrial cultures used to make Camembert and other bloomy rind cheeses. Over a period of just a few weeks, populations of wild Penicillium strains serially passaged on cheese had reduced pigment, spore, and mycotoxin production. Domesticated strains also had a striking change in volatile metabolite production, shifting from production of earthy or musty volatile compounds (e.g., geosmin) to fatty and cheesy volatiles (e.g., 2-nonanone, 2-undecanone). RNA sequencing demonstrated a significant decrease in expression of 356 genes in domesticated strains, with an enrichment of many secondary metabolite production pathways in these downregulated genes. By manipulating the presence of neighboring microbial species and overall resource availability, we demonstrate that the limited competition and high nutrient availability of the cheese environment promote rapid trait evolution of Penicillium molds.IMPORTANCE Industrial cultures of filamentous fungi are used to add unique aesthetics and flavors to cheeses and other microbial foods. How these microbes adapted to live in food environments is generally unknown as most microbial domestication is unintentional. Our work demonstrates that wild molds closely related to the starter culture Penicillium camemberti can readily lose traits and quickly shift toward producing desirable aroma compounds. In addition to experimentally demonstrating a putative domestication pathway for P. camemberti, our work suggests that wild Penicillium isolates could be rapidly domesticated to produce new flavors and aesthetics in fermented foods.

Fungal networks shape dynamics of bacterial dispersal and community assembly in cheese rind microbiomes.

Most studies of bacterial motility have examined small-scale (micrometer-centimeter) cell dispersal in monocultures. However, bacteria live in multispecies communities, where interactions with other microbes may inhibit or facilitate dispersal. Here, we demonstrate that motile bacteria in cheese rind microbiomes use physical networks created by filamentous fungi for dispersal, and that these interactions can shape microbial community structure. Serratia proteamaculans and other motile cheese rind bacteria disperse on fungal networks by swimming in the liquid layers formed on fungal hyphae. RNA-sequencing, transposon mutagenesis, and comparative genomics identify potential genetic mechanisms, including flagella-mediated motility, that control bacterial dispersal on hyphae. By manipulating fungal networks in experimental communities, we demonstrate that fungal-mediated bacterial dispersal can shift cheese rind microbiome composition by promoting the growth of motile over non-motile community members. Our single-cell to whole-community systems approach highlights the interactive dynamics of bacterial motility in multispecies microbiomes.

Development of corticostriatal connectivity constrains goal-directed behavior during adolescence.

When pursuing high-value goals, mature individuals typically titrate cognitive performance according to environmental demands. However, it remains unclear whether adolescents similarly integrate value-based goals to selectively enhance goal-directed behavior. We used a value-contingent cognitive control task during fMRI to assess how stakes-the value of a prospective outcome-modulate flexible goal-directed behavior and underlying neurocognitive processes. Here we demonstrate that while adults enhance performance during high stakes, adolescents perform similarly during low and high stakes conditions. The developmental emergence of value-contingent performance is mediated by connectivity between the striatum and prefrontal cortex; this connectivity selectively increases during high stakes and with age. These findings suggest that adolescents may not benefit from high stakes to the same degree adults do-a behavioral profile that may be constrained by ongoing maturation of corticostriatal connectivity. We propose that late development of corticostriatal connectivity sets the stage for optimal goal-directed behavior.

Disrupted Prefrontal Regulation of Striatal Subjective Value Signals in Psychopathy.

Psychopathy is a personality disorder with strong links to criminal behavior. While research on psychopathy has focused largely on socio-affective dysfunction, recent data suggest that aberrant decision making may also play an important role. Yet, the circuit-level mechanisms underlying maladaptive decision making in psychopathy remain unclear. Here, we used a multi-modality functional imaging approach to identify these mechanisms in a population of adult male incarcerated offenders. Psychopathy was associated with stronger subjective value-related activity within the nucleus accumbens (NAcc) during inter-temporal choice and with weaker intrinsic functional connectivity between NAcc and ventromedial prefrontal cortex (vmPFC). NAcc-vmPFC connectivity strength was negatively correlated with NAcc subjective value-related activity; however, this putative regulatory pattern was abolished as psychopathy severity increased. Finally, weaker cortico-striatal regulation predicted more frequent criminal convictions. These data suggest that cortico-striatal circuit dysregulation drives maladaptive decision making in psychopathy, supporting the notion that reward system dysfunction comprises an important neurobiological risk factor.

Biotic Interactions Shape the Ecological Distributions of Staphylococcus Species.

Many metagenomic sequencing studies have observed the presence of closely related bacterial species or genotypes in the same microbiome. Previous attempts to explain these patterns of microdiversity have focused on the abiotic environment, but few have considered how biotic interactions could drive patterns of microbiome diversity. We dissected the patterns, processes, and mechanisms shaping the ecological distributions of three closely related Staphylococcus species in cheese rind biofilms. Paradoxically, the most abundant species (S. equorum) is the slowest colonizer and weakest competitor based on growth and competition assays in the laboratory. Through in vitro community reconstructions, we determined that biotic interactions with neighboring fungi help resolve this paradox. Species-specific stimulation of the poor competitor by fungi of the genus Scopulariopsis allows S. equorum to dominate communities in vitro as it does in situ Results of comparative genomic and transcriptomic experiments indicate that iron utilization pathways, including a homolog of the S. aureus staphyloferrin B siderophore operon pathway, are potential molecular mechanisms underlying Staphylococcus-Scopulariopsis interactions. Our integrated approach demonstrates that fungi can structure the ecological distributions of closely related bacterial species, and the data highlight the importance of bacterium-fungus interactions in attempts to design and manipulate microbiomes. IMPORTANCE: Decades of culture-based studies and more recent metagenomic studies have demonstrated that bacterial species in agriculture, medicine, industry, and nature are unevenly distributed across time and space. The ecological processes and molecular mechanisms that shape these distributions are not well understood because it is challenging to connect in situ patterns of diversity with mechanistic in vitro studies in the laboratory. Using tractable cheese rind biofilms and a focus on coagulase-negative staphylococcus (CNS) species, we demonstrate that fungi can mediate the ecological distributions of closely related bacterial species. One of the Staphylococcus species studied, S. saprophyticus, is a common cause of urinary tract infections. By identifying processes that control the abundance of undesirable CNS species, cheese producers will have more precise control on the safety and quality of their products. More generally, Staphylococcus species frequently co-occur with fungi in mammalian microbiomes, and similar bacterium-fungus interactions may structure bacterial diversity in these systems.

Medial prefrontal functional connectivity--relation to memory self-appraisal accuracy in older adults with and without memory disorders.

It is tentatively estimated that 25% of people with early Alzheimer's disease (AD) show impaired awareness of disease-related changes in their own cognition. Research examining both normative self-awareness and altered awareness resulting from brain disease or injury points to the central role of the medial prefrontal cortex (MPFC) in generating accurate self-appraisals. The current project builds on this work - examining changes in MPFC functional connectivity that correspond to impaired self-appraisal accuracy early in the AD time course. Our behavioral focus was self-appraisal accuracy for everyday memory function, and this was measured using the Memory Function Scale of the Memory Awareness Rating Scale - an instrument psychometrically validated for this purpose. Using regression analysis of data from people with healthy memory (n=12) and people with impaired memory due to amnestic mild cognitive impairment or early AD (n=12), we tested the hypothesis that altered MPFC functional connectivity - particularly with other cortical midline structures and dorsolateral prefrontal cortex - explains variation in memory self-appraisal accuracy. We spatially constrained (i.e., explicitly masked) our regression analyses to those regions that work in conjunction with the MPFC to evoke self-appraisals in a normative group. This empirically derived explicit mask was generated from the result of a psychophysiological interaction analysis of fMRI self-appraisal task data in a separate, large group of cognitively healthy individuals. Results of our primary analysis (i.e., the regression of memory self-appraisal accuracy on MPFC functional connectivity) were generally consistent with our hypothesis: people who were less accurate in making memory self-appraisals showed attenuated functional connectivity between the MPFC seed region and proximal areas within the MPFC (including subgenual anterior cingulate cortex), bilateral dorsolateral prefrontal cortex, bilateral caudate, and left posterior hippocampus. Contrary to our expectations, MPFC functional connectivity with the posterior cingulate was not significantly related to accuracy of memory self-appraisals. Results reported here corroborate findings of variable memory self-appraisal accuracy during the earliest emergence of AD symptoms and reveal alterations in MPFC functional connectivity that correspond to impaired memory self-appraisal.

Calorie restriction reduces the influence of glucoregulatory dysfunction on regional brain volume in aged rhesus monkeys.

Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19-31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships.

Calorie restriction reduces psychological stress reactivity and its association with brain volume and microstructure in aged rhesus monkeys.

BACKGROUND: Heightened stress reactivity is associated with hippocampal atrophy, age-related cognitive deficits, and increased risk for Alzheimer's disease. This temperament predisposition may aggravate age-associated brain pathology or be reflective of it. This association may be mediated through repeated activation of the stress hormone axis over time. Dietary interventions, such as calorie restriction (CR), affect stress biology and may moderate the pathogenic relationship between stress reactivity and brain in limbic and prefrontal regions. METHODS: Rhesus monkeys (Macaca mulatta) aged 19-31 years consumed either a standard diet (N=18) or were maintained on 30% CR relative to baseline intake (N=26) for 13-19 years. Behavior was rated in both normative and aversive contexts. Urinary cortisol was collected. Animals underwent magnetic resonance imaging and diffusion tensor imaging (DTI) to acquire volumetric and tissue microstructure data respectively. Voxel-wise statistics regressed a global stress reactivity factor, cortisol, and their interaction on brain indices across and between dietary groups. RESULTS: CR significantly reduced stress reactivity during aversive contexts without affecting activity, orientation, or attention behavior. Stress reactivity was associated with less volume and tissue density in areas important for emotional regulation and the endocrine axis including prefrontal cortices, hippocampus, amygdala, and hypothalamus. CR reduced these relationships. A Cortisol by Stress Reactivity voxel-wise interaction indicated that only monkeys with high stress reactivity and high basal cortisol demonstrated lower brain volume and tissue density in prefrontal cortices, hippocampus, and amygdala. CONCLUSIONS: High stress reactivity predicted lower volume and microstructural tissue density in regions involved in emotional processing and modulation. A CR diet reduced stress reactivity and regional associations with neural modalities. High levels of cortisol appear to mediate some of these relationships.

Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus monkeys.

Higher serum homocysteine (Hcy) levels in humans are associated with vascular pathology and greater risk for dementia, as well as lower global and regional volumes in frontal lobe and hippocampus. Calorie restriction (CR) in rhesus monkeys (Macaca mulatta) may confer neural protection against age- or Hcy-related vascular pathology. Hcy was collected proximal to a magnetic resonance imaging (MRI) acquisition in aged rhesus monkeys and regressed against volumetric and diffusion tensor imaging indexes using voxel-wise analyses. Higher Hcy was associated with lower white matter volume in pons and corpus callosum. Hcy was correlated with lower gray matter volume and density in prefrontal cortices and striatum. CR did not influence Hcy levels. However, control monkeys exhibited a strong negative correlation between Hcy and global gray matter, whereas no relationship was evident for the CR monkeys. Similar group differences were also seen across modalities in the splenium of the corpus callosum, prefrontal cortices, hippocampus, and somatosensory areas. The data suggest that CR may ameliorate the influence of Hcy on several important age-related parameters of parenchymal health.

White matter in aging and cognition: a cross-sectional study of microstructure in adults aged eighteen to eighty-three.

Structural brain change and concomitant cognitive decline are the seemingly unavoidable escorts of aging. Despite accumulating studies detailing the effects of age on the brain and cognition, the relationship between white matter features and cognitive function in aging have only recently received attention and remain incompletely understood. White matter microstructure can be measured with diffusion tensor imaging (DTI), but whether DTI can provide unique information on brain aging that is not explained by white matter volume is not known. In the current study, the relationship between white matter microstructure, age, and neuropsychological function was assessed using DTI in a statistical framework that employed white matter volume as a voxel-wise covariate in a sample of 120 healthy adults across a broad age range (18-83). Memory function and executive function were modestly correlated with the DTI measures while processing speed showed the greatest extent of correlation. The results suggest that age-related white matter alterations underlie age-related declines in cognitive function. Mean diffusivity and fractional anisotropy in several white matter brain regions exhibited a nonlinear relationship with age, while white matter volume showed a primarily linear relationship with age. The complex relationships between cognition, white matter microstructure, and white matter volume still require further investigation.

Low HDL Cholesterol is Associated with Lower Gray Matter Volume in Cognitively Healthy Adults.

Dyslipidemia is common in adults and contributes to high rates of cardiovascular disease and may be linked to subsequent neurodegenerative and neurovascular diseases. This study examined whether lower brain volumes and cognition associated with dyslipidemia could be observed in cognitively healthy adults, and whether apolipoprotein E (APOE) genotype or family history of Alzheimer's disease (FHAD) alters this effect. T1-weighted magnetic resonance imaging was used to examine regional brain gray matter (GM) and white matter (WM) in 183 individuals (58.4 +/- 8.0 years) using voxel-based morphometry. A non-parametric multiple linear regression model was used to assess the effect of high-density lipoprotein (HDL) and non-HDL cholesterol, APOE, and FHAD on regional GM and WM volume. A post hoc analysis was used to assess whether any significant correlations found within the volumetric analysis had an effect on cognition. HDL was positively correlated with GM volume in the bilateral temporal poles, middle temporal gyri, temporo-occipital gyri, and left superior temporal gyrus and parahippocampal region. This effect was independent of APOE and FHAD. A significant association between HDL and the Brief Visuospatial Memory Test was found. Additionally, GM volume within the right middle temporal gyrus, the region most affected by HDL, was significantly associated with the Controlled Oral Word Association Test and the Center for Epidemiological Studies Depression Scale. These findings suggest that adults with decreased levels of HDL cholesterol may be experiencing cognitive changes and GM reductions in regions associated with neurodegenerative disease and therefore, may be at greater risk for future cognitive decline.