The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core: A culturally informed, community-engaged research (CI-CER) model to advance brain health equity.

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core was launched to advance Alzheimer's disease (AD) and AD-related dementia (ADRD) health equity research in underrepresented populations (URPs). We describe our evidence-based, scalable culturally informed, community-engaged research (CI-CER) model and demonstrate its preliminary success in increasing URP enrollment. METHODS: URPs include ethnoculturally minoritized, lower education (≤ 12 years), and rural populations. The CI-CER model includes: (1) culturally informed methodology (e.g., less restrictive inclusion/exclusion criteria, sociocultural measures, financial compensation, results disclosure, Spanish Language Capacity Workgroup) and (2) inclusive engagement methods (e.g., the Engagement Core team; Hub Sites; Community-Science Partnership Board). RESULTS: As of April 2024, 60% of ADNI-4 new in-clinic enrollees were from ethnoculturally or educationally URPs. This exceeds ADNI-4's ≥ 50% URP representation goal for new enrollees but may not represent final enrollment. DISCUSSION: Findings show a CI-CER model increases URP enrollment in AD/ADRD clinical research and has important implications for clinical trials to advance health equity. HIGHLIGHTS: The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) uses a culturally informed, community-engaged research (CI-CER) approach. The CI-CER approach is scalable and sustainable for broad, multisite implementation. ADNI-4 is currently exceeding its inclusion goals for underrepresented populations.

Shape of the past: Revealing detail arcs while narrating memories of autobiographical life events across the lifespan.

Humans can remember past autobiographical events through extended narratives. How these narrated memories typically unfold, however, remains largely unexplored. We evaluated how autobiographical memory details typically come together in a sample of 235 healthy young, middle-aged, and older adults. We found that details providing background knowledge followed a U shape, such that they were most prevalent in the initial moments of remembering before falling and then rising near the conclusion of the memory's retelling. Details about the scene of the memory declined over time, whereas other event-specific, unique details about the main features of the event followed an inverted U shape, peaking around the midpoint of a remembered event's narration. Whereas most detail arcs were not significantly affected by older age, older adults showed a significant underuse of details describing the scene early in memory retrieval. Our findings suggest that behind the ability to narrate the remembered past is a normative waxing and waning of the details that make autobiographical memories.

Underestimating the Relationship: Unpacking Both Socioeconomic Resources and Cognitive Function and Decline in Midlife to Later Life.

Although there is robust evidence that socioeconomic position influences later-life cognitive function, two issues limit knowledge regarding the nature and magnitude of these relationships and potential policy interventions. First, most social science research tends to treat cognition as a unitary concept despite evidence that cognitive outcomes are not interchangeable. Second, most biomedical research focuses exclusively on education, with limited attention to economic resources despite robust social science theoretical and empirical rationales for their role. Relatedly, there has been limited attention to how these relationships may vary across cohorts, even as educational and economic contexts have changed. Using the Health and Retirement Study (N = 36,494), we show that failing to attend to different facets of cognition, socioeconomic resources, and cohort differences leads to underestimates in the magnitude of educational and economic disparities in cognitive function and decline. This has important implications for appropriate policy interventions to address these disparities.

Metabolic kinetics and muscle and brain health markers in older adults, and the role of age and presence of chronic morbidities: A large cross-sectional cohort study.

BACKGROUND & AIMS: Older adults are at risk for muscle and cognitive function decline during advanced aging, but the underlying metabolic mechanisms and the role of aging-associated chronic morbidities remain unclear. In the present study, we examined whether protein and amino acid kinetics in older adults with and without chronic morbidities are different when 50-70 and 70-90 of age and related to markers of muscle and brain health declines. METHODS: In a large cross-sectional observational study, 575 older adults from 12 trials (2014-2022) were stratified based on their age (50-70y vs. 70-95y) and the presence of chronic morbidities. The main outcomes were whole-body production (WBP) and interconversions of amino acids by stable amino acid tracers, body composition, and muscle and cognitive performance. Additionally, the association between metabolic markers and muscle and brain health was assessed. RESULTS: Overall lower muscle strength, muscle and fat mass, and cognitive function (p < 0.03), but no mood disturbances, were found in 70-95y compared to 50-70y older adults. Presence of morbidities was associated with lower muscle strength and mass, and cognitive function, but higher visceral adipose tissue, and mood disturbances (p < 0.05). Aging was associated with suppressed WBP of most amino acids, de novo arginine production, and net protein breakdown, but higher myofibrillar protein breakdown (p < 0.007). Presence of morbidities was associated with lower WBP of glutamine, glutamate, histidine, isoleucine, phenylalanine, tyrosine, and net protein breakdown, and higher WBP of valine and taurine (p < 0.04). Age showed significant negative correlations with WBP of nearly all amino acids, de novo arginine production and net protein breakdown (r: [-0.407, -0.136], p < 0.01) but a positive correlation with WBP of myofibrillar protein breakdown (r = 0.133, p = 0.009). Lean mass showed positive correlations with de novo arginine production and net protein breakdown and WBP of all amino acids except for isoleucine (r: [0.16, 0.799], p < 0.005). MoCA showed a positive correlation with WBP of leucine and valine (r: [0.163, 0.2], p < 0.03). Worse cognitive performance was positively associated with WBP of tau-methylhistidine and taurine (r: [0.13, 0.141], p < 0.04), but negatively associated with WBP of glycine and valine, de novo arginine production, and net protein breakdown (r: [-0.222, -0.115], p < 0.05). CONCLUSION: Comprehensive phenotyping of a large group of older adults revealed differences in metabolic health in response to advanced aging and chronic morbidities. Poor muscle health accompanied by advanced aging was associated with overall metabolic downregulation, except for enhanced myofibrillar (muscle) protein breakdown. Presence of chronic morbidities was further associated with disturbed muscle health, mood, arginine, and taurine pathways, and higher visceral adipose tissue. Therefore, different phenotypes among older adults need to be considered when evaluating therapeutic approaches to improve muscle and brain health.

Attention, working memory, and inhibitory control in aging: Comparing amateur singers, instrumentalists, and active controls.

Despite the ubiquity of musical activities, little is known about the specificity of their association with executive functions. In this cross-sectional study, we examined this relationship as a function of age. Our main hypotheses were that executive functions would decline in older age, that this relationship would be reduced in singers and instrumentalists compared to nonmusician active controls, and that the amount of musical experience would be more strongly associated with executive functions compared to the specific type of activity. A sample of 122 cognitively healthy adults aged 20-88 years was recruited, consisting of 39 amateur singers, 43 amateur instrumentalists, and 40 nonmusician controls. Tests of auditory processing speed, auditory selective attention, auditory and visual inhibitory control, and auditory working memory were administered. The results confirm a negative relationship between age and executive functions. While musicians' advantages were found in selective attention, inhibitory control, and auditory working memory, these advantages were specific rather than global. Furthermore, most of these advantages were independent of age and experience. Finally, there were only limited differences between instrumentalists and singers, suggesting that the relationship between music-making activities and executive functions may be, at least in part, general as opposed to activity-specific.

Healthy Aging: Interaction of Cognition, Lifestyle, and Instrumental Activities of Daily Living.

Background: The increasing elderly population highlights the importance of comprehending healthy aging by examining the interactions among cognition, daily activities, and lifestyle. This study aims to address this by investigating these relationships within the World Health Organization's Healthy Aging Model. Methodology: A cross-sectional study was conducted with 178 older adults from southern Iran, representing various cognitive levels. Participants underwent assessments to measure cognitive functions, lifestyle preferences, and independence in instrumental activities of daily living (IADL) using the Mini-Mental State Examination, the Lifestyle Assessment Questionnaire for the Iranian Elderly, and the Lawton IADL Scale. Findings: The relationships between the studied variables were identified. Lower cognitive function was found to be associated with decreased engagement in IADL and less-favorable lifestyle choices. Conclusion: Integrating cognition, IADL, and lifestyle into assessments and interventions align with both the domain and process of occupational therapy, thereby enhancing well-being and promoting healthy aging in older adults.

Understanding Healthy Aging: How Lifestyle Choices, Cognitive Function, and Instrumental Daily Activities Interact in the ElderlyAs the global population of older individuals continues to increase, it is imperative to understand the impact of lifestyle choices, cognitive function, and instrumental daily activities on the aging process. The World Health Organization advocates for healthy aging by emphasizing individual abilities and potentials. This research explores these relationships within the older adult demographic in Iran. Cognitive function has been identified as a critical factor in maintaining independence in instrumental daily activities and in adopting healthy lifestyle behaviors. Individuals with diminished cognitive abilities may face challenges in tasks such as financial management or medication adherence, and they are more likely to demonstrate suboptimal lifestyle practices, such as limited engagement in physical exercise and stress management. These findings highlight the importance of assessing cognitive function alongside older adults' participation in instrumental daily activities and lifestyle choices to obtain a thorough evaluation of healthy aging. This research emphasizes the importance of prioritizing daily living aspects alongside cognitive health for healthy aging in geriatrics. Identifying individuals at risk of functional decline and unhealthy lifestyle habits can help implement tailored interventions to maintain or improve their ability to independently perform daily tasks and adopt healthier behaviors. Encouraging attitudes that value activities such as regular physical exercise and engaging in mentally stimulating activities are crucial for enhancing the overall well-being of older individuals.

The Common Marmoset as a Translational Model for Longitudinal Studies of Cognitive Aging and Individual Vulnerability to Decline.

In humans, cognitive aging is highly variable, with some individuals experiencing decline while others remain stable, and different cognitive domains exhibiting uneven vulnerability to aging. The neural mechanisms driving this intra- and inter-individual variability are not fully understood, making longitudinal studies in translational models essential for elucidating the timelines and processes involved. The common marmoset (Callithrix jacchus), a short-lived nonhuman primate, offers an unprecedented opportunity to conduct longitudinal investigations of aging and age-related disease over a condensed time frame, in a highly translatable animal model. The potential of the marmoset as a model for cognitive aging is indisputable, but a comprehensive cognitive battery tailored for longitudinal aging studies has not yet been developed, applied, or validated. This represents a critical missing piece for evaluating the marmoset as a model and understanding the extent to which marmoset cognitive aging mirrors the patterns found in humans, including whether marmosets have individual variability in their vulnerability to age-related cognitive decline. To address this, we developed a comprehensive touchscreen-based neuropsychological test battery for marmosets (MarmoCog), targeting five cognitive domains: working memory, stimulus-reward association learning, cognitive flexibility, motor speed, and motivation. We tested a large cohort of marmosets, ranging from young adults to geriatrics, over several years. We found significant variability in cognitive aging, with the greatest decline occurring in domains dependent on the prefrontal cortex and hippocampus. Additionally, we observed significant inter-individual variability in vulnerability to age-related cognitive decline: some marmosets declined across multiple domains, others in just one, and some showed no decline at all. This pattern mirrors human cognitive aging, solidifies the marmoset as an advantageous model for age-related cognitive decline, and provides a strong foundation for identifying the neural mechanisms involved.

Interpersonal, Community, and Societal Stressors Mediate Black-White Memory Disparities.

OBJECTIVES: Structural racism creates contextual stressors that disproportionately affect Black, relative to White, older adults in the United States and may contribute to worse cognitive health. We examined the extent to which interpersonal, community, and societal stressors uniquely explain Black-White disparities in initial memory and memory change. METHODS: The sample included 14,199 non-Latino Black and White older adults (Mage = 68.32, 19.8% Black) from the U.S. Health and Retirement Study who completed psychosocial questionnaires at baseline and a word list memory task every 2 years over an 8-year period. Interpersonal, community, and societal stressors were operationalized as self-reported everyday discrimination, neighborhood physical disorder, and subjective societal status, respectively. Latent growth curves modeled longitudinal memory performance. Stressors were modeled simultaneously and allowed to correlate. Covariates included age, sex, education, wealth, parental education, and Southern residence. RESULTS: Compared to White participants, Black participants experienced more discrimination (ß = -0.004, standard error [SE] = 0.001, p < .001), more neighborhood physical disorder (ß = -0.009, SE = 0.002, p < .001), and lower perceived societal status (ß = -0.002, SE = 0.001, p = .001), each of which uniquely mediated the racial disparity in initial memory. Sensitivity analyses utilizing proxy-imputed memory scores revealed an additional racial disparity in memory change, wherein Black participants evidenced a faster decline than White participants. This disparity in memory change was only uniquely mediated by more everyday discrimination among Black participants. DISCUSSION: Elements of structural racism may contribute to cognitive disparities via disproportionate stress experiences at multiple contextual levels among Black older adults. Future research should consider multilevel protective factors that buffer against negative impacts of racism on health.

Neuropsychological and Health Literacy Correlates of Science Knowledge Among Older and Younger Healthy Adults.

Science knowledge refers to the depth and breadth of facts acquired within the life, social, and earth sciences, and it has implications for both public and personal health. Drawing from cognitive aging theory, we examine whether levels of science knowledge are associated with age, neuropsychological functioning, and personal health literacy. Fifty-two younger and fifty older healthy adults completed our telephone-based study that included a commonly used test of science knowledge, as well as measures of neuropsychological functioning, health literacy, and relevant descriptives (e.g., mood). Adjusting for other demographics and neuropsychological functioning, older adults had significantly lower science knowledge test scores than younger adults. In the full sample, lower science knowledge showed medium-to-large associations with episodic memory, executive functions, and health literacy, independent of years of education. These results suggest that older adults' science knowledge falls slightly below that of their younger counterparts and is independently associated with higher order neuropsychological functions and aspects of personal health, which may have implications for accessing, understanding, and using relevant public health information across the lifespan.

Inflammatory protein associations with brain MRI measures: Framingham Offspring Cohort.

INTRODUCTION: Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study. METHODS: Dementia and stroke-free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross-sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations. RESULTS: Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex-stratified analyses, associations were observed exclusively among males. DISCUSSION: We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups. HIGHLIGHTS: Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV. Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV. Higher levels of SCF and TWEAK, were associated with larger TCBV. Significance diminished in models adjusting for CVD risk factors. Associations were observed exclusively in males.

Propositional density: cognitive impairment and aging.

It is important to understand the relationship between cognitive abilities and language processing. Here, we explore a burgeoning area of research that harnesses semantic indices to predict cognitive impairment and track cognitive decline. One such index, propositional density, quantifies the information conveyed per language segment. Despite some variation stemming from methodological, sampling, and measurement differences, we suggest that propositional density has diagnostic and assessment value. This paper surveys existing studies that have used propositional density in the context of cognitive aging and impairment and offers some insights into the use of this index to highlight differences in cognition. We also suggest further explorations of basic research involving this concept, and some applications for assessing cognitive health.

Attitudes Towards Dementia Among a Diverse Group of Refugees Resettled in the United States.

BACKGROUND: Forced migration results in exposure to trauma, interrupted access to healthcare, and loss of social support and may increase dementia risk. Literature on refugees' knowledge of dementia and its risk factors is scant. This study investigates refugee perspectives on dementia and their access to cognitive healthcare in the United States (US). METHODS: We conducted 6 focus groups and 30 individual in-depth interviews (total of 69 participants) with Arab, African, and Afghan refugees resettled in San Diego, California. Data was coded using inductive thematic analysis. RESULTS: Organized by the socioecological model of health, the following themes emerged: (1) mental trauma due to migration was linked to dementia (individual); (2) fear of dementia and burdening caregivers due to limited support systems (interpersonal); (3) reliance on virtual communities for dementia information and the stress of local community loss increasing dementia risk (community); (4) healthcare providers, both in the US and in refugee camps, didn't address cognitive health concerns (institutions); and (5) discriminatory immigration and healthcare policies as barriers to healthy aging (policy). DISCUSSION: Despite being a heterogeneous group, refugees share specific experiences, knowledge gaps, and barriers to healthy aging. Tailored interventions and policies are needed to address this population's cognitive health needs. This includes addressing their mental health and social support concerns as well as training clinicians to screen for/discuss dementia with aging refugee patients.

Purpose in Life and Cognitive Function in the Malaysian Ageing and Retirement Study.

OBJECTIVES: Evidence for the association between purpose in life and cognitive health is primarily from North American and European samples. This study evaluates this association in a large sample from Malaysia, an upper-middle-income country in Southeast Asia. METHODS: Participants (N = 5,579) from the Malaysian Ageing and Retirement Study reported on their purpose in life and subjective memory and were administered tasks that measured episodic memory, verbal fluency, and overall cognitive function. RESULTS: Purpose was associated with better subjective memory (ß=.13), episodic memory (ß=.06), verbal fluency (ß=.12), and overall cognitive function (ß=.07) (ps < .001). The associations were similar across sex and retirement status; purpose was more strongly related to subjective memory and overall cognitive function among older participants. Behavioral/social factors accounted for up to one-third of the associations, but all associations remained statistically significant. CONCLUSIONS: The positive association between purpose and cognition generalizes to a middle-income country in Southeast Asia. Similar to Western samples, behavioral and social factors accounted for part but not all the association. More research is needed in lower- and other middle-income countries to fully evaluate generalizability. CLINICAL IMPLICATIONS: Purpose may help support healthier cognitive aging across diverse populations and be a useful target to improve cognitive aging outcomes.

Long-term food supplementation with sweet basil (Ocimum basilicum L.) prevents age-associated cognitive decline in female mice.

Background: Mild cognitive decline, a common issue in aging, affects memory, learning, and attention. Nutrition can influence cognition, and research indicates that Ocimum sp. (holy basil and sweet basil) leaf extracts may enhance cognition in rodents and humans. However, these studies do not address whether these benefits extend to fresh or dry leaves consumed in typical human diets, along with physiological aging. Aim: To investigate the effects of sweet basil supplementation on cognition in mature and aged female mice. Methods: Female C57bl mice were divided into four groups: 8-month-old mature adults and 18-month-old aged adults, each receiving either a control or supplemented diet. The supplemented diet included a mix of standard chow and fresh basil leaves, administered for 2-8 months. Cognitive and behavioral assessments were conducted using the novel object recognition (NOR), Morris water maze (MWM), and elevated plus maze (EPM) tasks, focusing on memory, learning, and anxiety. Results: No cognitive improvement was observed in mature mice. However, aged mice receiving long-term basil supplementation showed enhanced discrimination in NOR and stayed closer to the absent platform in MWM compared to nonsupplemented controls. While aging mice exhibited reduced anxiety-like behavior in EPM, basil supplementation prevented this reduction. Conclusion: Basil supplementation appears beneficial in elderly mice, potentially preventing age-related cognitive decline and behavioral changes. These findings support the benefits of basil consumption in cognition and underscore its potential role in promoting healthy aging. Incorporating basil into the diet at a younger age may preserve memory and mitigate behavioral changes as individuals age.

Social cognition and healthy aging: Cross-sectional associations of emotion perception, theory of mind, and emotional empathy.

OBJECTIVE: Older adults are identified to have reduced social cognitive performance compared to younger adults. However, few studies have examined age-associations throughout later life to determine whether these reductions continue with advancing age. METHOD: This study assesses cross-sectional associations of emotion perception, cognitive and affective theory of mind (ToM), and emotional empathy in a healthy sample of 157 adults aged 50-89 years (M = 65.31, SD = 9.00, 68% female sex). Emotion perception, cognitive ToM, and affective ToM were measured using The Awareness of Social Inference Test Short Form (TASIT-S), while affective ToM was also measured using Reading the Mind in the Eyes Revised (RME-R). Emotional empathy was measured using the Empathy Quotient. RESULTS: Multiple regression analyses, adjusting for multiple comparisons, revealed a moderate negative association between age and emotion perception for all emotions combined, as well as for sad and revolted expressions, but not happy, neutral, anxious, or angry expressions. Age had a negative, moderate association with first-order cognitive, second-order cognitive, and affective ToM measured using TASIT-S, but not RME-R. Age was not significantly associated with emotional empathy. CONCLUSIONS: This study contributes to the limited understanding of age-related associations of social cognitive performance throughout later life. This knowledge can inform future research examining the clinical utility of including social cognitive measures in neuropsychological screening and diagnostic tools for later-life neurological disorders.

Plasma markers of neurodegeneration, latent cognitive abilities and physical activity in healthy aging.

Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer's disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65-75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aß42/Aß40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.

A randomized, placebo-controlled trial of purified anthocyanins on cognitive function in individuals at elevated risk for dementia: Analysis of inflammatory biomarkers toward personalized interventions.

BACKGROUND: Dementia poses a significant global health challenge. Anthocyanins neutralize free radicals, modulate signaling pathways, inhibit pro-inflammatory genes, and suppress cytokine production and may thus have positive cognitive effects in people at increased risk of dementia. We aim to investigate the effects of purified anthocyanins on cognitive function in people at increased risk of dementia according to their inflammation status based on blood-based inflammatory biomarkers. METHODS: This is a secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial. Cluster analysis was performed to categorize two groups based on their individual inflammatory biomarker profile using multiplex sandwich ELISA for the quantitative measurement of cytokines. Descriptive statistics and longitudinal models assessed cognitive outcomes. The primary comparison was the group difference at week 24 based on a modified intention-to-treat analysis. RESULTS: Cluster analysis revealed two distinct inflammatory biomarker profiles. In Cluster 1 (high levels of inflammation biomarkers), anthocyanin treatment showed a statistically significant improvement on cognitive function compared to placebo at 24 weeks. No significant differences were observed in Cluster 2 (low levels of inflammation biomarkers). The demographic characteristics, cognitive scores, and biomarker distributions were similar between treatment groups at baseline. However, cluster 1 exhibited higher BMI, diabetes prevalence, medication usage, and lower HDL cholesterol levels. CONCLUSION: Individuals with elevated levels of inflammation markers benefited from anthocyanin treatment to enhance cognitive performance, whereas those with lower levels did not. The anti-inflammatory and antioxidant properties of anthocyanins make them a promising intervention, and future prospective trials in people with increased inflammation are warranted.

Neurovascular mechanisms of cognitive aging: Sex-related differences in the average progression of arteriosclerosis, white matter atrophy, and cognitive decline.

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data (N = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity. By applying a novel piecewise regression approach to our cross-sectional sample to support Granger-like temporal inferences, we show that, on average, a precipitous decline in cerebral arterial elasticity (measured with diffuse optical imaging of the cerebral arterial pulse; pulse-DOT) precedes an acceleration in the development of white matter lesions by nearly a decade, with women protected from these deleterious effects until approximately age 50, the average onset of menopause. By employing multiple-mediator path analyses while controlling for sex, we show that age may impair cognition via the sequential indirect effects of arteriosclerosis and white matter atrophy on fluid, but not crystallized, abilities. Importantly, we replicate these results using pulse pressure, an independent index of arterial health, thereby providing converging evidence for the central role of arteriosclerosis as an accelerating factor in normal and pathological aging and identifying robust sex-related differences in the progression of cerebral arteriosclerosis and white matter degradation.

Characterizing dog cognitive aging using spontaneous problem-solving measures: development of a battery of tests from the Dog Aging Project.

Companion dogs are a valuable model for aging research, including studies of cognitive decline and dementia. With advanced age, some dogs spontaneously develop cognitive impairments and neuropathology resembling features of Alzheimer's disease. These processes have been studied extensively in laboratory beagles, but the cognitive assays used in that context-which rely on time-consuming operant procedures-are not easily scalable to large samples of community-dwelling companion dogs. We developed a battery of five short-form tasks targeting three aspects of cognition that are impaired in Alzheimer's disease: spatial memory, executive functions, and social cognition. In Experiment 1, we tested a cross-sectional sample of dogs (N = 123) and estimated associations between age and task performance. Older dogs scored lower on measures of spatial learning, memory, and response flexibility, and spent less time near, but more time gazing at, the experimenter. We found no differences in associations between age and performance across dogs of different body masses, a proxy for expected lifespan. In Experiment 2, we demonstrated the feasibility of these measures in clinical settings (N = 35). Dogs meeting clinical criteria for moderate or severe cognitive impairment scored lower, on average, than dogs characterized as mildly impaired and healthy agers, although these distributions overlapped. However, few dogs in our study cohort met the criteria for moderate or severe impairment. The measures presented here show promise for deployment in large-scale longitudinal studies of companion dogs, such as the Dog Aging Project.

Relationship between respiratory function assessed by spirometry and mild cognitive impairment among community-dwelling older adults.

AIM: Aging is a major cause of cognitive dysfunction. It has also been reported that respiratory function may influence cognitive dysfunction. However, few studies have examined the relationship between cognitive function and respiratory function among community-dwelling older adults. This study aims to determine the relationship between respiratory function, assessed using spirometry, and mild cognitive impairment (MCI) in community-dwelling older adults. METHODS: This study included 419 participants aged 73 ± 1 years and 348 participants aged 83 ± 1 years from the SONIC cohort study (Septuagenarians Octogenarians Nonagenarians Investigation with Centenarians Study). Respiratory function was evaluated using %Vital Capacity (%VC), Forced Expiratory Volume 1 s (FEV1)/Forced Vital Capacity (FVC), and %Peak Expiratory Flow (%PEF). Airflow-limitation presence and stages were classified using FEV1/FVC. Cognitive function and MCI were assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). RESULTS: The MoCA-J score exhibited a declining trend as the airflow-limitation stage increased among study participants in the 83 ± 1 age group. The presence of airflow limitation was associated with MCI in the 83 ± 1 age group. Among the indicators of each respiratory function, low %PEF was found to be associated with an increased rate of MCI. Furthermore, low %VC has also been suggested to be associated with an increased rate of MCI in the 83 ± 1 age female group. CONCLUSIONS: Advanced airflow-limitation stages may exacerbate cognitive dysfunction in community-dwelling older adults. The presence of airflow limitation and low %VC may also be associated with cognitive dysfunction in older women. Consequently, reduced respiratory function may potentially be associated with MCI in community-dwelling older adults. Geriatr Gerontol Int 2024; 24: 1001-1007.