N-Glycan profile of the cell membrane as a probe for lipopolysaccharide-induced microglial neuroinflammation uncovers the effects of common fatty acid supplementation.

Altered N-glycosylation of proteins on the cell membrane is associated with several neurodegenerative diseases. Microglia are an ideal model for studying glycosylation and neuroinflammation, but whether aberrant N-glycosylation in microglia can be restored by diet remains unknown. Herein, we profiled the N-glycome, proteome, and glycoproteome of the human microglia following lipopolysaccharide (LPS) induction to probe the impact of dietary and gut microbe-derived fatty acids-oleic acid, lauric acid, palmitic acid, valeric acid, butyric acid, isobutyric acid, and propionic acid-on neuroinflammation using liquid chromatography-tandem mass spectrometry. LPS changed N-glycosylation in the microglial glycocalyx altering high mannose and sialofucosylated N-glycans, suggesting the dysregulation of mannosidases, fucosyltransferases, and sialyltransferases. The results were consistent as we observed the restoration effect of the fatty acids, especially oleic acid, on the LPS-treated microglia, specifically on the high mannose and sialofucosylated glycoforms of translocon-associated proteins, SSRA and SSRB along with the cell surface proteins, CD63 and CD166. In addition, proteomic analysis and in silico modeling substantiated the potential of fatty acids in reverting the effects of LPS on microglial N-glycosylation. Our results showed that N-glycosylation is likely affected by diet by restoring alterations following LPS challenge, which may then influence the disease state.

Semantic details in autobiographical memory narratives increase with age among younger adults.

It is well documented that older adults, compared to younger adults, produce fewer episodic details and more semantic details when recalling autobiographical memories. However, group comparisons have provided limited insight into the trajectories of detail generation across the lifespan. Utilising an open source dataset [Clark, I. A., & Maguire, E. A. (2023). Release of cognitive and multimodal MRI data including real-world tasks and hippocampal subfield segmentations. Scientific Data, 10(1), 1-29. https://doi.org/10.1038/s41597-022-01899-x], we examined how episodic and semantic detail generation varied with age among 194 younger adults, ages 20-41. We tested whether age differences were mediated by hippocampal subfield volumes and MTL resting-state functional connectivity. Results indicated that semantic details increased with age, while episodic details remained stable. We observed age differences in hippocampal subfield volumes and MTL connectivity, but these measures did not mediate age effects on semantic detail. Based on these and prior findings [Matijevic, S., Andrews-Hanna, J. R., Wank, A. A., Ryan, L., & Grilli, M. D. (2022). Individual differences in the relationship between episodic detail generation and resting state functional connectivity vary with age. Neuropsychologia, 166, 108138. https://doi.org/10.1016/j.neuropsychologia.2021.108138], we suggest a model of diverging episodic and semantic detail generation trajectories across the adult lifespan.

More than just risk for Alzheimer's disease: APOE ε4's impact on the aging brain.

The apolipoprotein Îµ4 (APOE ε4) allele is most commonly associated with increased risk for late-onset Alzheimer's disease (AD). However, recent longitudinal studies suggest that these risks are overestimated; most ε4 carriers will not develop dementia in their lifetime. In this article, we review new evidence regarding the impact of APOE ε4 on cognition among healthy older adults. We discuss emerging work from animal models suggesting that ε4 impacts brain structure and function in multiple ways that may lead to age-related cognitive impairment, independent from AD pathology. We discuss the importance of taking an individualized approach in future studies by incorporating biomarkers and neuroimaging methods that may better disentangle the phenotypic influences of APOE ε4 on the aging brain from prodromal AD pathology.

DNA hydrogels for bone regeneration.

DNA-based biomaterials have been proposed for tissue engineering approaches due to their predictable assembly into complex morphologies and ease of functionalization. For bone tissue regeneration, the ability to bind Ca2+ and promote hydroxyapatite (HAP) growth along the DNA backbone combined with their degradation and release of extracellular phosphate, a known promoter of osteogenic differentiation, make DNA-based biomaterials unlike other currently used materials. However, their use as biodegradable scaffolds for bone repair remains scarce. Here, we describe the design and synthesis of DNA hydrogels, gels composed of DNA that swell in water, their interactions in vitro with the osteogenic cell lines MC3T3-E1 and mouse calvarial osteoblast, and their promotion of new bone formation in rat calvarial wounds. We found that DNA hydrogels can be readily synthesized at room temperature, and they promote HAP growth in vitro, as characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. Osteogenic cells remain viable when seeded on DNA hydrogels in vitro, as characterized by fluorescence microscopy. In vivo, DNA hydrogels promote the formation of new bone in rat calvarial critical size defects, as characterized by micro-computed tomography and histology. This study uses DNA hydrogels as a potential therapeutic biomaterial for regenerating lost bone.

Establishing the Validity and Reliability of an Online Motor Learning Game: Applications for Alzheimer's Disease Research Within MindCrowd.

Objective: Motor practice effects (i.e., improvements in motor task performance with practice) are emerging as a unique variable that can predict Alzheimer's disease (AD) progression and biomarker positivity. However, the tasks used to study motor practice effects have involved face-to-face assessment, making them difficult to integrate into large internet-based cohorts that represent the next generation of AD research. The purpose of this study was to validate an online computer game against its in-lab version, which has been shown previously to characterize motor practice effects. Materials and Methods: This study leveraged young adult participants within the MindCrowd electronic cohort, a large nationwide cohort for AD research collected entirely through the internet. Validation compared performance on the online version among MindCrowd users against an age-matched cohort's performance on an in-lab version using a different controller (Xbox 360 controller joystick for in-lab sample versus keyboard arrow keys for online sample). Results: Data indicated that the rate of skill acquisition among MindCrowd users were not significantly different from those of the in-lab cohort. Furthermore, the contact-to-consent rate observed in this study (although low) was similar to that of other online AD cohorts. Conclusion: Overall, this study demonstrates that implementing online games designed to study and measure motor practice effects into online research cohorts is feasible and valid. Future research will explore how online game performance is associated with age and dementia risk factors that may help further an understanding of AD.

CANNabinoid Drug Interaction Review (CANN-DIR™).

Non-prescription cannabidiol (CBD) and medical marijuana (cannabis) currently do not have US Food and Drug Administration (FDA)-approved prescribing information nor a dedicated resource to evaluate potential cannabinoid drug-drug interactions with other medications. The CANNabinoid Drug Interaction Review (CANN-DIR™) is a free web-based platform that has been developed to screen for potential drug-drug interactions from the perspective of how a cannabinoid delta-9-tetrahydrocannabinol (THC), CBD, or a combination of THC/CBD may affect the metabolism of another prescribed medication. CANN-DIR™ is based on FDA-approved prescribing information for the prescription cannabinoids (dronabinol, nabilone, nabiximols, and prescription CBD) and other FDA-approved prescribing information for medications sharing similar metabolic enzymes (e.g., the FDA "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers"). The Summary of Product Characteristics (SmPC) was the source of drug-drug interaction information for the combined ∆9-THC & CBD product nabiximols (Sativex®). CANN-DIR™ provides an expeditious review of cannabinoid drug-drug interaction information, and also a platform from which the patient and health care provider can print out the search results to either initiate a conversation, or for the health care provider to provide a written information sheet to supplement their verbal discussion. Additionally, to more effectively reach a global audience, the end user of CANN-DIR™ has the ability to currently navigate and print results in any of the following ten languages: Chinese, English, French, German, Nepali, Polish, Russian, Spanish, Swedish, and Vietnamese.

Past and future episodic detail retrieval is reduced among clinically normal older adults at higher genetic risk for late-onset Alzheimer's disease.

OBJECTIVE: Remembering and imagining personal events that are rich in episodic (i.e., event-specific) detail is compromised in older adults who have mild cognitive impairment, a known risk factor for Alzheimer's disease dementia. Less clear is whether lower episodic detail generation is associated with higher risk for Alzheimer's disease dementia before mild clinical decline is detectable. METHOD: We compared past and future autobiographical thinking in clinically normal older adult carriers of the Alzheimer's disease-associated apolipoprotein E e4 allele (APOE4; n = 39) to demographically and neuropsychologically similar non-APOE4 carriers (n = 43). RESULTS: APOE4 carriers showed a significant reduction for episodic details when remembering past events (d = .47) and imagining future events (d = .46), but not for nonepisodic details. CONCLUSIONS: These findings suggest that APOE4 is associated with a selective reduction of episodic detail during past and future autobiographical thinking among clinically normal older adults. Reduced episodic detail generation, therefore, may be an early cognitive associate of higher risk for Alzheimer's disease dementia. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The impact of context on pattern separation for objects among younger and older apolipoprotein ϵ4 carriers and noncarriers.

OBJECTIVE: On continuous recognition tasks, changing the context objects are embedded in impairs memory. Older adults are worse on pattern separation tasks requiring identification of similar objects compared to younger adults. However, how contexts impact pattern separation in aging is unclear. The apolipoprotein (APOE) ϵ4 allele may exacerbate possible age-related changes due to early, elevated neuropathology. The goal of this study is to determine how context and APOE status affect pattern separation among younger and older adults. METHOD: Older and younger ϵ4 carriers and noncarriers were given a continuous object recognition task. Participants indicated if objects on a Repeated White background, Repeated Scene, or a Novel Scene were old, similar, or new. The proportions of correct responses and the types of errors made were calculated. RESULTS: Novel scenes lowered recognition scores compared to all other contexts for everyone. Younger adults outperformed older adults on identifying similar objects. Older adults misidentified similar objects as old more than new, and the repeated scene exacerbated this error. APOE status interacted with scene and age such that in repeated scenes, younger carriers produced less false alarms, and this trend switched for older adults where carriers made more false alarms. CONCLUSIONS: Context impacted recognition memory in the same way for both age groups. Older adults underutilized details and over relied on holistic information during pattern separation compared to younger adults. The triple interaction in false alarms may indicate an even greater reliance on holistic information among older adults with increased risk for Alzheimer's disease.

Neuroimaging and verbal memory assessment in healthy aging adults using a portable low-field MRI scanner and a web-based platform: results from a proof-of-concept population-based cross-section study.

Consumer wearables and health monitors, internet-based health and cognitive assessments, and at-home biosample (e.g., saliva and capillary blood) collection kits are increasingly used by public health researchers for large population-based studies without requiring intensive in-person visits. Alongside reduced participant time burden, remote and virtual data collection allows the participation of individuals who live long distances from hospital or university research centers, or who lack access to transportation. Unfortunately, studies that include magnetic resonance neuroimaging are challenging to perform remotely given the infrastructure requirements of MRI scanners, and, as a result, they often omit socially, economically, and educationally disadvantaged individuals. Lower field strength systems (< 100 mT) offer the potential to perform neuroimaging at a participant's home, enabling more accessible and equitable research. Here we report the first use of a low-field MRI "scan van" with an online assessment of paired-associate learning (PAL) to examine associations between brain morphometry and verbal memory performance. In a sample of 67 individuals, 18-93 years of age, imaged at or near their home, we show expected white and gray matter volume trends with age and find significant (p < 0.05 FWE) associations between PAL performance and hippocampus, amygdala, caudate, and thalamic volumes. High-quality data were acquired in 93% of individuals, and at-home scanning was preferred by all individuals with prior MRI at a hospital or research setting. Results demonstrate the feasibility of remote neuroimaging and cognitive data collection, with important implications for engaging traditionally under-represented communities in neuroimaging research.

Individual differences in the relationship between episodic detail generation and resting state functional connectivity vary with age.

The ability to generate episodic details while recollecting autobiographical events is believed to depend on a collection of brain regions that form a posterior medial network (PMN). How age-related differences in episodic detail generation relate to the PMN, however, remains unclear. The present study sought to examine individual differences, and the role of age, in PMN resting state functional connectivity (rsFC) associations with episodic detail generation. Late middle-aged and older adults (N = 41, ages 52-81), and young adults (N = 21, ages 19-35) were asked to describe recent personal events, and these memory narratives were coded for episodic, semantic and 'miscellaneous' details. Independent components analysis and regions-of-interest analyses were used to assess rsFC within the PMN separately for anterior connections (hippocampal and medial prefrontal) and posterior connections (hippocampal, parahippocampal and parieto-occipital), as these connections purportedly serve different functional roles in episodic detail generation. Compared to younger adults, older adults produced memory narratives with lower episodic specificity (ratio of episodic:total details) and a greater amount of semantic detail. Among the older adults, episodic detail amounts and episodic specificity were reduced with increasing age. There were no significant age differences in PMN rsFC. Stronger anterior PMN rsFC was related to lower episodic detail in the older adult group, but not in the young. Among the older adults, increasing age brought on an association between increased anterior PMN rsFC and reduced episodic specificity. In contrast, increasing age brought on an association between increased posterior PMN rsFC and increased semantic detail. The present study provides evidence that functional connectivity within the PMN, particularly anterior PMN, tracks individual differences in the amount of episodic details retrieved by older adults. Furthermore, these brain-behavior relationships appear to be age-specific, indicating that some process within aging alters the nature of how anterior PMN rsFC and episodic detail relate to each other. Whether this process entails an age-related loss of integrity to the PMN, or an age-related shift toward semantic retrieval, remains to be determined.

Serum Neurofilament Light is elevated in COVID-19 Positive Adults in the ICU and is associated with Co-Morbid Cardiovascular Disease, Neurological Complications, and Acuity of Illness.

In critically ill COVID-19 patients, the risk of long-term neurological consequences is just beginning to be appreciated. While recent studies have identified that there is an increase in structural injury to the nervous system in critically ill COVID-19 patients, there is little known about the relationship of COVID-19 neurological damage to the systemic inflammatory diseases also observed in COVID-19 patients. The purpose of this pilot observational study was to examine the relationships between serum neurofilament light protein (NfL, a measure of neuronal injury) and co-morbid cardiovascular disease (CVD) and neurological complications in COVID-19 positive patients admitted to the intensive care unit (ICU). In this observational study of one-hundred patients who were admitted to the ICU in Tucson, Arizona between April and August 2020, 89 were positive for COVID-19 (COVID-pos) and 11 was COVID-negative (COVID-neg). A healthy control group (n=8) was examined for comparison. The primary outcomes and measures were subject demographics, serum NfL, presence and extent of CVD, diabetes, sequential organ failure assessment score (SOFA), presence of neurological complications, and blood chemistry panel data. COVID-pos patients in the ICU had significantly higher mean levels of Nfl (229.6 ± 163 pg/ml) compared to COVID-neg ICU patients (19.3 ± 5.6 pg/ml), Welch's t-test, p =.01 and healthy controls (12.3 ± 3.1 pg/ml), Welch's t-test p =.005. Levels of Nfl in COVID-pos ICU patients were significantly higher in patients with concomitant CVD and diabetes (n=35, log Nfl 1.6±.09), and correlated with higher SOFA scores (r=.5, p =.001). These findings suggest that in severe COVID-19 disease, the central neuronal and axonal damage in these patients may be driven, in part, by the level of systemic cardiovascular disease and peripheral inflammation. Understanding the contributions of systemic inflammatory disease to central neurological degeneration in these COVID-19 survivors will be important to the design of interventional therapies to prevent long-term neurological and cognitive dysfunction.

Remote, Unsupervised Functional Motor Task Evaluation in Older Adults across the United States Using the MindCrowd Electronic Cohort.

COVID-19 has impacted the ability to evaluate motor function in older adults, as motor assessments typically require face-to-face interaction. One hundred seventy-seven older adults nationwide completed an unsupervised functional upper-extremity assessment at home. Data were compared to data from an independent sample of community-dwelling older adults (N = 250) assessed in lab. The effect of age on performance was similar between the in-lab and at-home groups. Practice effects were also similar. Assessing upper-extremity motor function remotely is feasible and reliable in community-dwelling older adults. This test offers a practical solution for telehealth practice and other research involving remote or geographically isolated individuals.

Remote, unsupervised functional motor task evaluation in older adults across the United States using the MindCrowd electronic cohort.

The COVID-19 pandemic has impacted the ability to evaluate motor function in older adults, as motor assessments typically require face-to-face interaction. This study tested whether motor function can be assessed at home. One hundred seventy-seven older adults nationwide (recruited through the MindCrowd electronic cohort) completed a brief functional upper-extremity assessment at home and unsupervised. Performance data were compared to data from an independent sample of community-dwelling older adults (N=250) assessed by an experimenter in-lab. The effect of age on performance was similar between the in-lab and at-home groups for both the dominant and non-dominant hand. Practice effects were also similar between the groups. Assessing upper-extremity motor function remotely is feasible and reliable in community-dwelling older adults. This test offers a practical solution in response to the COVID-19 pandemic and telehealth practice and other research involving remote or geographically isolated individuals.

Tract Specificity of Age Effects on Diffusion Tensor Imaging Measures of White Matter Health.

Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54-92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.

Apolipoprotein E ε4 Allele-Based Differences in Brain Volumes Are Largely Uniform Across Late Middle Aged and Older Hispanic/Latino- and Non-Hispanic/Latino Whites Without Dementia.

Hispanics/Latinos are at an equal or a greater risk for Alzheimer's disease (AD), yet risk factors remain more poorly characterized as compared to non-Hispanic/Latino Whites. Among non-Hispanic/Latino White cohorts, the apolipoprotein E (APOE) ε4 allele is one of the strongest risk factors for AD with subtle declines in episodic memory and brain volumes detectable in the preclinical stages. We examined whether the APOE ε4 status had a differential impact on cognition and brain volumes among cognitively healthy and mild cognitively impaired Hispanics/Latinos (n = 86; ε4 n = 23) compared to a well-matched group of non-Hispanic/Latino Whites (n = 92; ε4 n = 29). Neither the APOE ε4 status nor the interaction between the ε4 status and ethnicity was associated with cognitive performance. The APOE ε4 status was associated with white matter and not with gray matter volumes. APOE ε4 carriers had a significantly smaller total brain white matter volumes, as well as smaller right middle temporal and left superior temporal volumes. The Hispanics/Latinos had significantly smaller left middle frontal gray matter volumes, yet marginally larger overall white matter volumes, than the non-Hispanic/Latino Whites. Exploratory analysis within the Hispanic/Latino sample found that those people whose primary language was Spanish had larger total brain white matter volumes compared primarily to the English speakers. Importantly, primary language differences only held for Hispanic/Latino ε4 carriers and did not differentiate Hispanic/Latino non-carriers, underscoring the need for further investigation into the impacts of language and acculturation on cognitive aging among the fastest growing ethnic minority group in the United States.

Graphene Quantum Dots as Intracellular Imaging-Based Temperature Sensors.

Non-invasive temperature sensing is necessary to analyze biological processes occurring in the human body, including cellular enzyme activity, protein expression, and ion regulation. To probe temperature-sensitive processes at the nanoscale, novel luminescence nanothermometers are developed based on graphene quantum dots (GQDs) synthesized via top-down (RGQDs) and bottom-up (N-GQDs) approaches from reduced graphene oxide and glucosamine precursors, respectively. Because of their small 3-6 nm size, non-invasive optical sensitivity to temperature change, and high biocompatibility, GQDs enable biologically safe sub-cellular resolution sensing. Both GQD types exhibit temperature-sensitive yet photostable fluorescence in the visible and near-infrared for RGQDs, utilized as a sensing mechanism in this work. Distinctive linear and reversible fluorescence quenching by up to 19.3% is observed for the visible and near-infrared GQD emission in aqueous suspension from 25 °C to 49 °C. A more pronounced trend is observed with GQD nanothermometers internalized into the cytoplasm of HeLa cells as they are tested in vitro from 25 °C to 45 °C with over 40% quenching response. Our findings suggest that the temperature-dependent fluorescence quenching of bottom-up and top-down-synthesized GQDs studied in this work can serve as non-invasive reversible/photostable deterministic mechanisms for temperature sensing in microscopic sub-cellular biological environments.

Autobiographical Memory Fluency Reductions in Cognitively Unimpaired Middle-Aged and Older Adults at Increased Risk for Alzheimer's Disease Dementia.

OBJECTIVE: Recent research has revealed that cognitively unimpaired older adults who are at higher risk for developing Alzheimer's disease (AD) dementia often exhibit subtle cognitive alterations in their neuropsychological profiles. Emerging evidence suggests that autobiographical memory, which is memory for personal events and knowledge, may be sensitive to early AD-related cognitive alterations. In the present study, we investigated whether the rapid generation of autobiographical memory category exemplars, a retrieval process that taxes the neural network that is vulnerable to early AD, is compromised in cognitively unimpaired middle-aged and older carriers of the e4 allele of the apolipoprotein E gene (APOE4), which increases risk for AD dementia. METHODS: In addition to standard neuropsychological tests, we administered a fluency task that requires generating exemplars for two types of autobiographical memory, namely episodic memories and personal semantics, to a group of cognitively unimpaired middle-aged and older adults (n = 45) enriched with APOE4 carriers (n = 20). RESULTS: While no APOE4 deficits were found on standard neuropsychological tests, episodic and personal semantic exemplar generation was reduced in the APOE4 group. DISCUSSION: Autobiographical memory aberrations associated with a higher risk for AD are evident in fluency and affect both episodic memory and personal semantics.

Cardiovascular risk factors and APOE-ε4 status affect memory functioning in aging via changes to temporal stem diffusion.

Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age-related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE-ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion-weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE-ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.

Differences between young and older adults in unity and diversity of executive functions.

Miyake and colleagues (2000) identified three independent but correlated components of executive function in young adults - set shifting, inhibition, and updating. The present study compared the factor structure in young adults to two groups of older adults (ages 60-73 and 74-98). A three-factor model of shifting, inhibition and updating was confirmed in young adults, but the factors were weakly or uncorrelated. In both older groups, a two-factor solution was indicated, updating/inhibition and shifting, which were moderately correlated in young-older adults, and strongly correlated in the old-older group. A nested factors model in the oldest group revealed a common factor, which loaded on all but one of the tests, and a shifting-specific factor. We concluded that in young adulthood, shifting, updating and inhibition may operate relatively independently. As people age and processing becomes less efficient, they may rely increasingly on general executive control processes, reallocating their limited resources to optimize performance.

Hypertension and Age-Related Cognitive Impairment: Common Risk Factors and a Role for Precision Aging.

PURPOSE OF REVIEW: Precision Aging® is a novel concept that we have recently employed to describe how the model of precision medicine can be used to understand and define the multivariate risks that drive age-related cognitive impairment (ARCI). Hypertension and cardiovascular disease are key risk factors for both brain function and cognitive aging. In this review, we will discuss the common mechanisms underlying the risk factors for both hypertension and ARCI and how the convergence of these mechanisms may be amplified in an individual to drive changes in brain health and accelerate cognitive decline. RECENT FINDINGS: Currently, our cognitive health span does not match our life span. Age-related cognitive impairment and preventing and treating ARCI will require an in-depth understanding of the interrelated risk factors, including individual genetic profiles, that affect brain health and brain aging. Hypertension and cardiovascular disease are important risk factors for ARCI. And, many of the risk factors for developing hypertension, such as diabetes, smoking, stress, viral infection, and age, are shared with the development of ARCI. We must first understand the mechanisms common to the converging risk factors in hypertension and ARCI and then design person-specific therapies to optimize individual brain health. The understanding of the convergence of shared risk factors between hypertension and ARCI is required to develop individualized interventions to optimize brain health across the life span. We will conclude with a discussion of possible steps that may be taken to decrease ARCI and optimize an individual's cognitive life span.