Global Cognitive Score Research Articles

Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons

BackgroundFindings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean–DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia.MethodsWe performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)–derived measures of brain characteristics in a nonrandom sample of participants.ResultsA total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, −0.022 to 0.092; P=0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups.ConclusionsAmong cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.)

Multi-session transcutaneous auricular vagus nerve stimulation for Parkinson's disease: evaluating feasibility, safety, and preliminary efficacy.

In pre-clinical animal models of Parkinson's disease (PD), vagus nerve stimulation (VNS) can rescue motor deficits and protect susceptible neuronal populations. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a non-invasive alternative to traditional invasive cervical VNS. This is the first report summarizing the safety, feasibility, and preliminary efficacy of repeated sessions of taVNS in participants with PD. To evaluate the feasibility, safety, and possible efficacy of taVNS for motor and non-motor symptoms in mild to moderate PD. This is a double-blind, sham controlled RCT (NCT04157621) of taVNS in 30 subjects with mild to moderate PD without cognitive impairment. Participants received 10, 1-h taVNS sessions (25 Hz, 200% of sensory threshold, 500 μs pulse width, 60 s on and 30 s off) over a 2-week period. Primary outcome measures were feasibility and safety of the intervention; secondary outcomes included the MDS-UPDRS, cognitive function and self-reported symptom improvement. taVNS treatment was feasible, however, daily in-office visits were reported as being burdensome for participants. While five participants in the taVNS group and three in the sham group self-reported one or more minor adverse events, no major adverse events occurred. There were no group differences on blood pressure and heart rate throughout the intervention. There were no group differences in MDS-UPDRS scores or self-reported measures. Although global cognitive scores remained stable across groups, there was a reduction in verbal fluency within the taVNS group. taVNS was safe, and well-tolerated in PD participants. Future studies of taVNS for PD should explore at-home stimulation devices and optimize stimulation parameters to reduce variability and maximize engagement of neural targets.

Hearing, β-Amyloid Deposition and Cognitive Test Performance in Black and White Older Adults: The ARIC-PET Study.

Hearing loss is a risk factor for dementia; whether the association is causal or due to a shared pathology is unknown. We estimated the association of brain β-amyloid with hearing, hypothesizing no association. As a positive control, we quantified the association of hearing loss with neurocognitive test performance. Cross-sectional analysis of Atherosclerosis Risk in Communities-Positron Emission Tomography study data. Amyloid was measured using global cortical and temporal lobe standardized uptake value ratios (SUVRs) calculated from florbetapir-positron emission tomography scans. Composite global and domain-specific cognitive scores were created from 10 neurocognitive tests. Hearing was measured using an average of better-ear air conduction thresholds (0.5-4 kHz). Multivariable-adjusted linear regression estimated mean differences in hearing by amyloid and mean differences in cognitive scores by hearing, stratified by race. In 252 dementia-free adults (72-92 years, 37% Black race, and 61% female participants), cortical or temporal lobe SUVR was not associated with hearing (models adjusted for age, sex, education, and APOE ε4). Each 10 dB HL increase in hearing loss was associated with a 0.134 standard deviation lower mean global cognitive factor score (95% CI: -0.248, -0.019), after adjustment for demographic and cardiovascular factors. Observed hearing-cognition associations were stronger in Black versus White participants. Amyloid is not associated with hearing, suggesting that pathways linking hearing and cognition are independent of this pathognomonic Alzheimer's-related brain change. This is the first study to show that the impact of hearing loss on cognition may be stronger in Black versus White adults.

Cognition in older adults with healthy aging: analysis of the Mexican Health and Aging Study 2012-2015.

Maintaining older adults' health and well-being can be achieved through the optimization of physical and mental health, while preserving independence, social participation, and quality of life. Cognitive change has been described as a normal process of aging and it involves domains such as processing speed, attention, memory, language, visuospatial abilities, and executive functioning, among others. To describe cognitive changes in older adults with healthy aging. This is a study that involved data from 14,893 and 14,154 individuals aged >60 years or older from the 2012 and 2015 waves, respectively, who participated in the Mexican Health and Aging Study (MHAS). Participants with healthy aging were identified and described in the MHAS-2012 wave and followed to 2015. Eight cognitive domains evaluated in the Cross-Cultural Cognitive Evaluation (CCCE,) as well as sociodemographic and health characteristics, were described. Criteria for healthy aging involved the following: CCCE ≥ -1.5 standard deviations above the mean on reference norms, independence on basic and instrumental activities of daily living, self-reported "life close to ideal," and preserved functional and social performance. From a total of n = 9,160 older adults from the MHAS-2012 wave, n = 1,080 (11.8%) had healthy aging. In the healthy aging group, the median age was 67 years (IQR: 63-73), 58.1% were female and the median for education was 6 (IQR: 3-8) years. The mean CCCE score was 57 (SD: 16.9) points. In the MHAS-2012 cross-sectional analysis, except for orientation, visuospatial abilities, and verbal fluency, all cognitive domain scores were lower with passing age. When comparing cognitive domain scores in the 225 older adults identified with healthy aging between the 2012 and 2015 MHAS waves, there were almost no observable differences. In the cross-sectional analysis, Mexican adults with healthy aging had lower scores in the verbal learning memory, visual scanning, numeracy, visual memory, and verbal recall domains', as well as lower global cognitive scores in the higher age groups. There were no cognitive changes in the 3 year follow-up, except for a lower gradient of scores in the verbal recall memory domain. Longer prospective studies are needed to characterize greater cognitive changes.

Association of Dietary Quality with Cognitive Function in Chinese Adults Aged 55 Years and Above: A Longitudinal Study.

Diet is an important modifiable factor for brain health and aging. Present study aimed to explore association of dietary quality with cognitive function and poor cognition in middle-aged and older adults participating in the China Health and Nutrition Survey (CHNS). A longitudinal study with a twenty-year follow-up. Data were drawn from the CHNS 1997, 2000, 2004, 2006, 2015 and 2018. Subjects aged 55 years and more who participated in at least two waves and had completed data on socio-demographics, lifestyle, disease history, anthropometrics, dietary measure and cognitive assessment were eligible in present study. Baseline diet were assessed by 3-day 24-hour dietary recalls and used to evaluate diet quality via China Elderly Dietary Guidelines Index 2022 (CDGI 2022-E). Cognitive function was examined using part items of the Telephone Interview for Cognitive Status-modified. Three-level linear mixed effects models and three-level mixed effects logistic regression models were performed to estimate the association between diet quality and cognitive function and odds of poor cognition, respectively. At baseline, 4173 subjects with median age of 63.7 years were recruited. Median of CDGI 2022-E total score was 44.7. Median score of global cognition was 16.0, and the proportion of people with poor cognitive function was 13.9%. Difference in global cognitive score was observed by tertiles of CDGI 2022-E (p<0.05). Significant associations of high diet quality with increment in global cognitive score [β (95%CI): 0.704 (0.394~1.015)], composite cognitive z score [0.086 (0.045~0.128)] and standardized verbal memory score [0.221 (0.122~0.320)] were observed in total subjects. Consistent associations were also found in those below 65 years at baseline. The likelihood of poor cognition in the highest tertile of CDGI 2022-E decreased by 18% (95%CI: 0.698~0.965) relative to the lowest tertile group in total population. High diet quality may be beneficial for improving cognitive function and delaying cognitive decline in Chinese middle-aged and older population.

Dietary low- and high-quality carbohydrate intake and cognitive decline: A prospective cohort study in older adults

The association of dietary intake of carbohydrate (CHO), especially high- and low-quality CHO, with the decline of cognitive function remains uncertain. We aimed to investigate the prospective association of dietary total, low- and high-quality CHO intake with cognitive decline, and further examine the effect of isocaloric substitution with protein or fat, in the elderly population. A total of 3106 Chinese participants aged ≥55 years from China Health and Nutrition Survey (CHNS) were included in this study. Dietary nutrient intake information was collected by 24-h dietary recalls on 3 consecutive days. The cognitive decline was defined as the 5-year decline rates in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified (TICS-m). The median follow-up duration was 5.9 years. There was a significantly positive association of dietary low-quality CHO (per 10 percentage energy [%E] increment, β, 0.06; 95%CI, 0.01-0.11) and a no significant association of dietary high-quality CHO (per 10%E increment, β, 0.04; 95%CI,-0.07-0.14) with the 5-year decline rate in the composite cognitive scores. Similar results were found for the global cognitive scores. In model simulations, substituting dietary low-quality CHO with isocaloric animal protein or fat, instead of isocaloric plant protein or fat, was significantly and inversely associated with cognitive decline (All P values<0.05). The dietary intake of low-quality CHO, rather than high-quality CHO, was significantly associated with a faster cognitive decline in the elderly. In model simulations, isocaloric substitution of dietary low-quality CHO with animal protein or fat, rather than plant protein or fat, was inversely associated with cognitive decline.

Midlife Neuropsychological Profiles and Associated Vascular Risk: The Bogalusa Heart Study.

Individuals with Alzheimer's disease (AD) often present with coexisting vascular pathology that is expressed to different degrees and can lead to clinical heterogeneity. To examine the utility of unsupervised statistical clustering approaches in identifying neuropsychological (NP) test performance subtypes that closely correlate with carotid intima-media thickness (cIMT) in midlife. A hierarchical agglomerative and k-means clustering analysis based on NP scores (standardized for age, sex, and race) was conducted among 1,203 participants (age 48±5.3 years) from the Bogalusa Heart Study. Regression models assessed the association between cIMT ≥50th percentile and NP profiles, and global cognitive score (GCS) tertiles for sensitivity analysis. Three NP profiles were identified: Mixed-low performance [16%, n = 192], scores ≥1 SD below the mean on immediate, delayed free recall, recognition verbal memory, and information processing; Average [59%, n = 704]; and Optimal [26%, n = 307] NP performance. Participants with greater cIMT were more likely to have a Mixed-low profile [OR = 3.10, 95% CI (2.13, 4.53), p < 0.001] compared to Optimal. After adjusting for education and cardiovascular (CV) risks, results remained. The association with GCS tertiles was more attenuated [lowest (34%, n = 407) versus highest (33%, n = 403) tertile: adjusted OR = 1.66, 95% CI (1.07, 2.60), p = 0.024]. As early as midlife, individuals with higher subclinical atherosclerosis were more likely to be in the Mixed-low profile, underscoring the potential malignancy of CV risk as related to NP test performance, suggesting that classification approaches may aid in identifying those at risk for AD/vascular dementia spectrum illness.

Application and validation of an algorithmic classification of early impairment in cognitive performance

Objective Due to the long prodromal period for dementia pathology, approaches are needed to detect cases before clinically recognizable symptoms are apparent, by which time it is likely too late to intervene. This study contrasted two theoretically-based algorithms for classifying early cognitive impairment (ECI) in adults aged ≥50 enrolled in the Baltimore Longitudinal Study of Aging. Method Two ECI algorithms were defined as poor performance (1 standard deviation [SD] below age-, sex-, race-, and education-specific means) in: (1) Card Rotations or California Verbal Learning Test (CVLT) immediate recall and (2) ≥1 (out of 2) memory or ≥3 (out of 6) non-memory tests. We evaluated concurrent criterion validity against consensus diagnoses of mild cognitive impairment (MCI) or dementia and global cognitive scores using receiver operating characteristic (ROC) curve analysis. Predictive criterion validity was evaluated using Cox proportional hazards models to examine the associations between algorithmic status and future adjudicated MCI/dementia. Results Among 1,851 participants (mean age = 65.2 ± 11.8 years, 50% women, 74% white), the two ECI algorithms yielded comparably moderate concurrent criterion validity with adjudicated MCI/dementia. For predictive criterion validity, the algorithm based on impairment in Card Rotations or CVLT immediate recall was the better predictor of MCI/dementia (HR = 3.53, 95%CI: 1.59–7.84) over 12.3 follow-up years. Conclusions Impairment in visuospatial ability or memory may be capable of detecting early cognitive changes in the preclinical phase among cognitively normal individuals.

Trends in cognitive function before and after stroke in China

BackgroundWhile cognitive impairment after stroke is common, cognitive trends before stroke are poorly understood, especially among the Chinese population who have a relatively high stroke burden. We aimed to model the trajectories of cognitive function before and after new-onset stroke among Chinese.MethodsA total of 13,311 Chinese participants aged ≥ 45 years and without a history of stroke were assessed at baseline between June 2011 and March 2012 and in at least one cognitive test between 2013 (wave 2) and 2018 (wave 4). Cognitive function was assessed using a global cognition score, which included episodic memory, visuospatial abilities, and a 10-item Telephone Interview of Cognitive Status (TICS-10) test to reflect calculation, attention, and orientation abilities.ResultsDuring the 7-year follow-up, 610 (4.6%) participants experienced a first stroke. Both stroke and non-stroke groups showed declined cognitive function during follow-up. After adjustment for covariates, there was no significant difference in pre-stroke cognitive trajectories between stroke patients and stroke-free participants. The stroke group showed an acute decline in episodic memory (− 0.123 SD), visuospatial abilities (− 0.169 SD), and global cognition (− 0.135 SD) after stroke onset. In the years following stroke, the decline rate of the TICS-10 test was higher than the rate before stroke (− 0.045 SD/year).ConclusionsChinese stroke patients had not experienced steeper declines in cognition before stroke compared with stroke-free individuals. Incident stroke was associated with acute declines in global cognition, episodic memory, visuospatial abilities, and accelerated declines in calculation, attention, and orientation abilities.

Complement proteins in serum astrocyte-derived exosomes are associated with mild cognitive impairment in type 1 diabetes mellitus patients

BackgroundThe complement system plays a crucial role in cognitive impairment. The aim of this study is to investigate the correlation between the complement proteins levels in serum astrocyte-derived exosomes (ADEs) and mild cognitive impairment (MCI) in type 1 diabetes mellitus (T1DM) patients. MethodsIn this cross-sectional study, the patients with immune-mediated T1DM were enrolled. Healthy subjects matched for age and sex with T1DM patients were selected as controls. The cognitive function was evaluated by a Beijing version of the Montreal Cognitive Assessment (MoCA) questionnaire. The complement proteins including C5b-9, C3b and Factor B in serum ADEs were measured by ELISA kits. ResultsThis study recruited 55 subjects immune-mediated T1DM patients without dementia, including 31 T1DM patients with MCI, 24 T1DM patients without MCI. 33 healthy subjects were enrolled as controls. The results showed higher complement proteins including C5b-9, C3b and Factor B levels in ADEs from T1DM patients with MCI than those in the controls (P < 0.001, P < 0.001, P = 0.006) and T1DM patients without MCI (P = 0.02, P = 0.02, P = 0.03). The C5b-9 levels in ADEs were independently associated with MCI in T1DM patients(OR: 1.20, 95% CI: 1.00–1.44, P = 0.04). The C5b-9 levels in ADEs were significantly correlated with global cognitive scores (β = -0.360, P＜0.001) and visuo-executive (β = -0.132, P＜0.001), language(β = -0.036, P = 0.026) and delayed recall score (β = -0.090,P = 0.007). There was no correlation between the C5b-9 levels in ADEs and the fasting glucose, HbA1c, fasting c-peptide and GAD65 antibody in T1DM patients. Furthermore, the C5b-9, C3b and Factor B levels in ADEs exhibited a fair combined diagnostic value for MCI, with an area under the curve of 0.76 (95% CI: 0.63–0.88, P = 0.001). ConclusionThe elevated C5b-9 levels in ADEswere significantly associated with theMCI in T1DM patients. The C5b-9 in ADEs may be used as a marker of MCI in T1DM patients.

Brain free‐water increases in mild behavioral impairment

AbstractBackgroundMild behavioural impairment (MBI) is proposed as a diagnostic construct to identify dementia‐free individuals with sustained neuropsychiatric symptoms as an early manifestation of dementia. Our previous study has demonstrated that MBI predicts faster cognitive decline and progression to dementia. Other studies have shown that MBI was associated with Alzheimer’s disease biomarkers for Aβ and tau. However, cerebrovascular disease (CeVD), which is another critical pathology in dementia, has not been investigated in MBI. Here, we sought to test brain free‐water (FW) alterations, a marker for CeVD, in MBI compared with non‐MBI participants and their associations with longitudinal changes in cognition, function, and neuropsychiatric symptoms.MethodLongitudinal global cognitive scores, clinical dementia rating sum‐of‐boxes (CDR‐SoB), neuropsychiatric inventory (NPI) scores, over 5 years were reported in 281 dementia‐free participants (40 MBI and 241 non‐MBI). MBI was diagnosed using established criteria. All participants underwent T1‐weighted structural and diffusion MRI at baseline. FW imaging method was applied to derive individual‐level white matter (WM) and grey matter (GM) FW maps from diffusion MRI. We compared baseline GM‐FW and WM‐FW between non‐MBI and MBI subjects. We then tested the associations of MBI‐related FW increase with baseline and longitudinal changes in global cognition, CDR‐SB, and NPI scores using linear regression models.ResultMBI had greater GM‐FW in executive control (prefrontal), motor sensory (precentral), attention (insula) and memory (left temporal and right cingulate and cuneus) networks and widespread higher WM‐FW compared with non‐MBI (Fig‐1). Both higher GM‐FW and WM‐FW were associated with lower global cognition, higher CDR‐SB, and higher NPI scores across all participants at baseline (Table‐1). There was no interaction effect of MBI status on such association. Moreover, higher baseline GM‐FW and WM‐FW were associated with longitudinal worsening in global cognition, CDR‐SB, and NPI scores (Table‐2). Interestingly, such associations were greater in MBI than in non‐MBI (Fig‐2).ConclusionThis study demonstrated that MBI was associated with increased brain FW, which may have contributed to the relationship between persistent neuropsychiatric disturbances and clinical and cognitive outcomes. Early detection of cerebrovascular‐related FW alteration may allow for timely management of MBI individuals before development of dementia.

The association between Alzheimer’s disease blood‐based biomarkers and cognitive impairment and probable dementia in Look AHEAD MIND

AbstractBackgroundThe effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study.MethodParticipants aged 45‐76 years were randomized at baseline to a 10‐year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8‐18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end‐of‐intervention plasma samples were analyzed with the Quanterix Simoa HD‐X Analyzer. Changes in Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z‐scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE‐ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing.ResultThe mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration &gt;5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (‐0.04 ±0.01; p = 0.002), global cognition scores (‐0.05 ±0.02; p = 0.011), executive function (‐0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR] 1.10, 95% CI 1.02‐1.19). Increases in GFAP predicted lower memory (‐0.10 ±0.03; p = 0.0001), global cognition (‐0.09 ±0.03; p = 0.009), executive function scores (‐0.12 ±0.03; p&lt;0.0001), and increased risk of MCI/probable dementia (OR 1.24, 95% CI 1.09‐1.41).ConclusionThere was no association between the intervention and changes in biomarker levels. Increasing levels of NfL and GFAP over the ∼10 year period were associated with reduced cognitive performance and increased risk of MCI/probable dementia.

Dementia associated disorders, cognitive impairment and impact on social roles activities and participation: Patient centric impact

AbstractBackgroundDementia associated diseases (DAD) refers to several clinical conditions that are characterized by progressive cognitive impairment that interferes with an individual’s ability to function independently. Cognitive impairments (CI) can vary in degree and combination across multiple cognitive domains (CD) that routine care or tests (MMSE, MOCA) might not adequately identify. Therefore, a clinician may not recognize these varied types of CI or change in CD scores effectively. Enhanced recognition of patient centric CI in routine care can be accomplished improved analytics by incorporating a validated, examiner independent computerized cognitive assessment battery (CAB‐NT). Patient self‐reported outcome measures (PRO) are concurrently incorporated with CAB‐NT to gauge associated disability progression. Ability and participation in social roles and activities and communication ability can adversely affect quality of life (QoL) for people with Dementia associated diseases (PwDAD) and are likely related to CI and other factors.MethodRetrospective review of consecutive PwDAD who completed both CAB‐NT and PRO (SSRA, APSRA, and C‐SF) on the same day in the course of routine care. CAB‐NT included 7 cognitive domains: memory (Mem), executive function (Exe), attention (Att), information processing speed (Inf), visual spatial (Vis), verbal function (Ver), motor skills (Mot) as well as a global cognitive summary score (GCS).Results312 PwDaD, 64.74% female, average age 66 +/‐ 17 years. Simple linear regression analyses were performed with significant correlations (p = &lt;0.05): CAB‐NT vs SSRA: GCS r = 0.2, Exe r = 0.3, Mot r = 0.2, and Att r = 0.3. CAB‐NT vs APSRA: Exe r = 0.3, Att r = 0.2. CAB‐NT vs C‐SF: Exe r = 0.2.ConclusionSocial roles and communication in PwDAD are most impacted by CI associated with executive functioning and attention. Impairment in these domains are associated with increased difficulty for PwDaD to effectively interact with others and may lead to reduced QoL for these patients. Identifying the degree and combination of such CI precisely might allow for early and effective targeted proactive behavioral and/or medicinal intervention to improve QOL of these patients.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: While oral targeted therapies (OTT) have transformed the care of patients (pts) with lymphoma, adherence, cost, and chronic low-grade toxicities with subsequent impact on health-related quality of life (HRQoL) remain challenging issues. There are limited data on HRQoL in older adults (OA), who tend to be more vulnerable to treatment-related adverse effects. We prospectively evaluated the role of geriatric assessment (GA) in predicting HRQoL and adherence in OA with lymphoma on OTT. Methods: Pts ≥70 years (yrs) with lymphoma, initiating or already on OTT were included. A GA was performed at baseline; pt, disease, and OTT characteristics were recorded. Pts were followed monthly for the first 3 months (mos), then every 3 mos for 1 year. QoL was measured at each visit using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (EORTC QLQ-C30) and EORTC QLQ- chronic lymphocytic leukemia 16 (EORTC QLQ-CLL16) modules. The log QoL scores were modeled as a function of visit and mean scores at 12 months were compared to baseline using a linear mixed model. Results: We enrolled 50 pts. Median age was 77 yrs (70–93 yrs) with 88% pts having at least 1 geriatric syndrome (GS), including cognitive impairment (22%), depression (24%), polypharmacy (86%) and falls (16%); 50% pts had ≥2 GS; 50% having an impaired 4-meter gait speed (<1 m/s); 46% having an abnormal timed-up-and-go (TUG) time (>10s) and 86% had an adjusted CIRS-G score of ≥6. OTT included ibrutinib (54%), venetoclax (26%) and acalabrutinib (12%). At baseline, advancing age, activities of daily living (ADL) dependence, and instrumental activities of daily living (IADL) dependence were associated with inferior global health status, physical functioning, role functioning, and cognitive functioning scores. IADL dependence was also associated with worse social functioning and most symptoms scores. An abnormal TUG was associated with lower global health score (p = 0.002) and cognitive functioning (p = 0.003). At the end of 1 year, there was a statistically significant worsening of global health status (mean difference -8.4, p = 0.003) without any changes in other functional scales; however, it did not reach the predefined criterion for clinical relevance (absolute difference of >10, Figure 1). Only impaired baseline TUG was associated with significant worsening of global health status (-1.9 vs. -23.2, p = 0.048), physical (4.1 vs. -8.2, p = 0.031), role (1.3 vs. -18.5, p = 0.026) and social functioning (5.1 vs. -24.1, p = 0.016), and increasing fatigue scale (-11.5 vs. 20.4, p < 0.001) over 1 year. Other geriatric impairments did not impact changes in HRQoL over time. The research was funded by: Roswell Park Alliance Foundation Keywords: Cancer Health Disparities, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. P. Torka Consultant or advisory role: Genenetech, GenMab, Lilly USA, Seagen

Protocol development to study launch: The Australian‐multidomain approach to reduce dementia risk by protecting brain health With lifestyle intervention (AU‐ARROW) study

AbstractBackgroundThe Finnish Geriatric Intervention Study (FINGER) reported that a multidomain lifestyle intervention could provide an effective and accessible means of protecting against age‐related cognitive decline and dementia. This led to the global dementia risk reduction initiative: World‐Wide FINGERS (WW‐FINGERS). As part of WW‐FINGERS, the AU‐ARROW study mirrors aspects of FINGER, as well as the U.S. study (US‐POINTER, also part of WW‐FINGERS), while allowing for Australian cultural and dietary adaptations.MethodAU‐ARROW is a randomised, single‐blind, 2‐year clinical trial, recruiting 600 participants aged 60‐79, who satisfy study‐specific eligibility inclusion/exclusion criteria. Participants will be recruited at (a) Macquarie University, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and randomised into either the multimodal lifestyle intervention (ML) group or the Health Education and Coaching (HC) group. The ML group will engage in a) aerobic exercise, resistance training and stretching facilitated by local gym memberships, b) monthly telehealth diet monitoring and advice, to encourage MIND diet adherence whilst aligning with Australian Dietary Guidelines, c) online BrainHQ cognitive training sessions, and d) medical monitoring and health education sessions. The HC group will receive occasional health education sessions. All participants receive heart rate trackers, 6‐monthly blood tests, regular health monitoring and clinician advice.ResultAU‐ARROW’s primary outcome measure involves assessment of changes in a global composite cognitive score, measured using neurocognitive tests as in US‐POINTER. Further neurocognitive tests, lifestyle questionnaires, physical function tests, diet and sleep monitoring will determine specific contributions of the various lifestyle changes. Extra value will emanate from Alzheimer’s disease (AD) biomarker analysis of blood and urine samples collected yearly, as well as AD Aβ amyloid‐specific ligand‐PET imaging, brain MRI and retinal biomarker tests at 0 and 24 months. The final AU‐ARROW protocol design and methods will be presented. Initial recruitment data may also be presented.ConclusionThe finalised AU‐ARROW protocol is expected to facilitate study completion and maximise data sources, and allow a) development of an evidence‐based innovative treatment plan to reduce cognitive decline and dementia risk, b) effective transfer of research outcomes into Australian health policy, and c) validation of emerging blood and retinal diagnostic biomarkers in preclinical screening.

Association between social support and cognitive function

AbstractBackgroundObservational studies suggest social support is associated with vulnerability for cognitive decline in older adults. Because of racial/ethnic homogeneity in prior studies beings predominantly in White/European ancestry, less is known about the generalization of these putative psychosocial mechanisms. Thus, we evaluated whether better telecommunication social support systems were associated with better cognitive performance using a unique longitudinal cohort of rural South African older adults.MethodWe conducted a cross‐sectional study using 541 participants from the HAALSI (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) Dementia Cohort. Participants’ exposure to social support via telecommunication was measured using a standard assessment. Cognitive performance was measured using a neuropsychological battery validated in this population that assesses the domains consistent with the Alzheimer’s Disease Research Centers Uniform Data Set. Raw scores were converted into z scores and a composite global cognitive score was created as an additional indicator of global cognition. We examined cross‐sectional associations with multivariate robust regression analysis using robust S‐estimation. Telecommunication social support was modeled as the independent variable; cognitive measures were modeled as dependent variables.ResultHigher telecommunication social support was associated with better global cognitive function after adjustment for age, gender, and education (β:0.01, 95% CI: 0.006, 0.022). This association persisted after additional adjustments for depressive symptoms and vascular risk factors. Higher telecommunication social support was also associated with cognitive function assessed by mini mental status examination and tests of executive function and memory.ConclusionTelecommunication‐based social support was associated with higher levels of cognitive performance in a rural South African cohort of Black older adults. Although these findings and the potential of reverse causality need to be further validated, our results suggest that intervention studies might be specifically merited to understand whether promoting social support through telecommunication in similar samples of older adult populations lessen vulnerability for cognitive decline.

CUMULATIVE BLOOD PRESSURE LOAD AND INCIDENT DEMENTIA, COGNITIVE FUNCTION, AND ALL-CAUSE AND CARDIOVASCULAR DEATHS IN ADULTS AGED 70 YEARS AND OLDER

Objective: Few studies have focused on the contribution of long-term exposure to elevated BP to dementia and deaths, particularly among older adults. We examined the prognostic value of cumulative BP (cBP) and cBP load in relation to incident dementia, cognitive decline, all-cause and cardiovascular deaths among adults aged 70 years and above, followed over 15 years. We also explored whether seated vs standing BP has more predictive value for these outcomes. Design and method: The Sydney Memory and Aging Study (N = 1,037) comprised a cohort of community-dwelling individuals aged 70 - 90 years without dementia, recruited from two areas of Sydney, Australia. Baseline data collection was performed in 2005-2007 and the cohort was followed every two years for 7 waves until 2021. Sitting and standing systolic, diastolic BP and pulse pressure (PP) were measured from wave 1 to 3. Cumulative sitting and standing BP and its load were calculated from the area under the curve. We assessed the association of BP parameters with incident dementia, cognitive function, all-cause and cardiovascular deaths between wave 4 and 7, in Cox proportional hazards models. Results: A total of 520 participants with three waves of BP data were included (47.7% men, median age at baseline, 77 [IQR: 74 - 81] years). In the multivariable-adjusted Cox model, cumulative pulse pressure (cPP) load was associated with a higher risk of dementia (sitting p for trend = 0.004; standing p for trend = 0.023), and lower global cognitive scores (sitting p for trend = 0.005; standing p for trend = 0.022). However, no significant associations were found upon additional age adjustment (p for tend&gt;0.05). Sitting and standing cPP and cPP load were also associated with higher risk of all-cause deaths (all p for trend &lt; 0.006). No associations were found for cumulative systolic or diastolic sitting or standing BP and dementia and cognition, as well as all-cause and cardiovascular deaths in both crude and adjusted models. Conclusions: Long-term cPP load predicted a significant age-dependent increase in risk for dementia, cognitive decline, and deaths in adults older than 70 years.

Associations of Microvascular Dysfunction with Mild Cognitive Impairment and Cognitive Function Among Rural-Dwelling Older Adults in China.

Microvascular dysfunction (MVD) may contribute to cognitive impairment and Alzheimer's disease, but evidence is limited. To investigate the association of composite and organ-specific MVD burden with mild cognitive impairment (MCI) and cognition among rural-dwelling Chinese older adults. In this population-based cross-sectional study, we assessed MVD makers using optical coherence tomographic angiography for retinal microvasculature features, brain magnetic resonance imaging scans for cerebral small vessel disease (CSVD), and serum biomarkers for MVD. A composite MVD score was generated from the aforementioned organ-specific parameters. We used a neuropsychological test battery to assess memory, verbal fluency, attention, executive function, and global cognitive function. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were diagnosed following the Petersen's criteria. Data was analyzed with the linear and logistic regression models. Of the 274 dementia-free participants (age≥65 years), 56 were diagnosed with MCI, including 47 with aMCI and 9 with naMCI. A composite MVD score was statistically significantly associated with an odds ratio (OR) of 2.70 (95% confidence interval 1.12-6.53) for MCI and β-coefficient of -0.29 (-0.48--0.10) for global cognitive score after adjustment for socio-demographics, lifestyle factors, APOE genotype, the Geriatric Depression Scale score, serum inflammatory biomarkers, and cardiovascular comorbidity. A composite score of retinal microvascular morphology was associated with a multivariable-adjusted OR of 1.72 (1.09-2.73) for MCI and multivariable-adjusted β-coefficient of -0.11 (-0.22--0.01) for global cognitive score. A composite CSVD score was associated with a lower global cognitive score (β= -0.10; -0.17--0.02). Microvascular dysfunction, especially in the brain and retina, is associated with MCI and poor cognitive function among rural-dwelling older adults.

0087 Associations between AHA’s Life’s Essential 8 and cognition in a sample of diverse midlife adults

Abstract Introduction Life’s Simple 7 (LS7), originally proposed as the seven most important predictors of heart health, is associated with negative cognitive outcomes. Recently an updated Life’s Essential 8 (LE8) added sleep as the new eighth component. However, limited research has investigated LE8 and cognitive outcomes. We hypothesize that a higher composite LE8 score will be associated with better cognitive performance. Methods Cross-sectional analyses were conducted including 1498 adults (36-76 years old, 41% male, 61% African American) from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study who completed all LE8 and global cognition measurements in wave 4 data collection (2013-2017). Blood pressure, glucose, cholesterol, BMI, diet, physical activity, and smoking were calculated based on available wave 4 data per LE8 scoring guidance. The sleep component was scored based on the sleep duration question from the Pittsburgh Sleep Quality Index (“During the past month, how many hours of actual sleep did you get at night?”). LE8 score was calculated by averaging the scores from the eight components. Cognitive performance was measured from a Joggle battery to calculate a total global cognition score and individual domains (memory, attention, visual orientation, executive function, speed). A set of linear regression analyses were performed. Covariates included biological age, sex, race, poverty status, sleep apnea, education attainment (high school), reading literacy, and depression (CES-D). Results Higher scores on LE8 were significantly associated with better global cognitive performance, even after adjusting for covariates (b=0.024, p = .014). Among all cognitive domains, higher LE8 scores were significantly associated with better memory (b = 0.011, p &amp;lt; .001), attention (b=0.012, p = .007), but not visual orientation, executive function, or speed. Conclusion Better cardiovascular health, as indicated by a higher LE8 composite score, is associated with better cognitive performance among U.S. middle-aged and older adults. Future studies may further explore this relationship using longitudinal data and explore the predictive power of each LE8 component. Support (if any) UF1AG072619 (PI: Gamaldo)

Minding your steps: a cross-sectional pilot study using foot-worn inertial sensors and dual-task gait analysis to assess the cognitive status of older adults with mobility limitations

BackgroundCognitive impairment is a critical aspect of our aging society. Yet, it receives inadequate intervention due to delayed or missed detection. Dual-task gait analysis is currently considered a solution to improve the early detection of cognitive impairment in clinical settings. Recently, our group proposed a new approach for the gait analysis resorting to inertial sensors placed on the shoes. This pilot study aimed to investigate the potential of this system to capture and differentiate gait performance in the presence of cognitive impairment based on single- and dual-task gait assessments.MethodsWe analyzed demographic and medical data, cognitive tests scores, physical tests scores, and gait metrics acquired from 29 older adults with mobility limitations. Gait metrics were extracted using the newly developed gait analysis approach and recorded in single- and dual-task conditions. Participants were stratified into two groups based on their Montreal Cognitive Assessment (MoCA) global cognitive scores. Statistical analysis was performed to assess differences between groups, discrimination ability, and association of gait metrics with cognitive performance.ResultsThe addition of the cognitive task influenced gait performance of both groups, but the effect was higher in the group with cognitive impairment. Multiple dual-task costs, dual-task variability, and dual-task asymmetry metrics presented significant differences between groups. Also, several of these metrics provided acceptable discrimination ability and had a significant association with MoCA scores. The dual-task effect on gait speed explained the highest percentage of the variance in MoCA scores. None of the single-task gait metrics presented significant differences between groups.ConclusionsOur preliminary results show that the newly developed gait analysis solution based on foot-worn inertial sensors is a pertinent tool to evaluate gait metrics affected by the cognitive status of older adults relying on single- and dual-task gait assessments. Further evaluation with a larger and more diverse group is required to establish system feasibility and reliability in clinical practice.Trial registrationClinicalTrials.gov (identifier: NCT04587895)