Cognitive Composite Score Research Articles

How brain structure-function decoupling supports individual cognition and its molecular mechanism.

Functional signals emerge from the structural network, supporting multiple cognitive processes through underlying molecular mechanism. The link between human brain structure and function is region-specific and hierarchical across the neocortex. However, the relationship between hierarchical structure-function decoupling and the manifestation of individual behavior and cognition, along with the significance of the functional systems involved, and the specific molecular mechanism underlying structure-function decoupling remain incompletely characterized. Here, we used the structural-decoupling index (SDI) to quantify the dependency of functional signals on the structural connectome using a significantly larger cohort of healthy subjects. Canonical correlation analysis (CCA) was utilized to assess the general multivariate correlation pattern between region-specific SDIs across the whole brain and multiple cognitive traits. Then, we predicted five composite cognitive scores resulting from multivariate analysis using SDIs in primary networks, association networks, and all networks, respectively. Finally, we explored the molecular mechanism related to SDI by investigating its genetic factors and relationship with neurotransmitter receptors/transporters. We demonstrated that structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. We revealed better performance in cognition prediction is achieved by using high-level hierarchical SDIs, with varying significance of different brain regions in predicting cognitive processes. We found that the SDIs were associated with the gene expression level of several receptor-related terms, and we also found the spatial distributions of four receptors/transporters significantly correlated with SDIs, namely D2, NET, MOR, and mGluR5, which play an important role in the flexibility of neuronal function. Collectively, our findings corroborate the association between hierarchical macroscale structure-function decoupling and individual cognition and provide implications for comprehending the molecular mechanism of structure-function decoupling. PRACTITIONER POINTS: Structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. High-level hierarchical structure-function decoupling contributes much more than low-level decoupling to individual cognition. Structure-function decoupling could be regulated by genes associated with pivotal receptors that are crucial for neuronal function flexibility.

The CogniAid trial. The impact of two hearing aid signal processing strategies on cognition

BackgroundUntreated hearing loss is a risk factor for age-related cognitive decline and hearing aids have been shown to slow cognitive decline in a population at risk for dementia. This double-blind multiple site randomized trial tested the hypothesis that for older adults with below-average cognition, a “Simple” hearing aid fitting strategy (based on linear amplification with output limiting compression signal processing) would improve hearing and cognition more than a “Standard” approach (adaptive compression-based processing).MethodsTwo hundred and fifty-six adults aged over 65 were screened for cognitive function using the NIH toolbox cognitive battery. Participants with below median age-adjusted fluid composite cognitive scores (<100) were eligible to participate (n = 104). Sixty-seven eligible participants proceeded to trial and were randomized 1:1 to a simple or standard hearing aid fitting. Participants in the Standard group were fitted with hearing aids matched to non-linear real-ear prescription targets (either NAL-NL1 or NL2), while participants in the Simple group were fitted with hearing aids matched to linear prescription targets (NAL-R). Participants and researchers not fitting the hearing aids were blinded to allocation.ResultsForty-eight participants completed assessments in 12 months. The Standard hearing aid group improved on measures of fluid cognition and hearing. There was a statistically significant difference in fluid cognition scores between groups. The fluid cognition composite score for participants receiving the Simple fitting changed by 3.5 points. Those with the Standard fitting improved by 10.3 points. Hearing outcomes for each group were improved by the same amount.ConclusionThis is the first study to show that hearing aid fitting strategies using markedly different signal processing result in significantly different cognitive outcomes after 12 months of use. The Standard fitting resulted in greater improvement in cognition than the Simpler fitting which was the opposite result to what had been hypothesized. The results reinforce findings indicating hearing aid benefits for the elderly and that they improve cognition.

Prodromal Cognitive Changes as a Prognostic Indicator of Forthcoming Huntington's Disease Severity: A Retrospective Longitudinal Study.

Cognitive changes in Huntington's disease (HD) precede motor manifestations. ENROLL-HD platform includes four cognitive measures of information processing speed (IPS). Our group is eager to seek clinical markers in the life stage that is as close as possible to the age of onset (ie, the so called prodromal HD phase) because this is the best time for therapeutic interventions. Our study aimed to test whether cognitive scores in prodromal ENROLL-HD mutation carriers show the potential to predict the severity of motor and behavioral changes once HD became fully manifested. From the global ENROLL-HD cohort of 21,343 participants, we first selected a premanifest Cohort#1 (ie, subjects with Total Motor Score (TMS) <10 and Diagnostic Confidence Level (DCL) <4, N = 1.222). From this cohort, we then focused on a prodromal Cohort#2 of subjects who were ascertained to phenoconvert into manifest HD at follow-up visits (ie, subjects from 6 ≤ TMS≤9 and DCL <4 to TMS≥10 and DCL = 4, n = 206). The main results of our study showed that low IPS before phenoconversion in Cohort#2 predicted the severity of motor and behavioral manifestations. By combining the four IPS cognitive measures (eg, the Categorical Verbal Fluency Test; Stroop Color Naming Test; Stroop Word Reading; Symbol Digit Modalities Test), we generated a Composite Cognition Score (CCS). The lower the CCS score the higher the TMS and the apathy scores in the same longitudinally followed-up patients after phenoconversion. CCS might represent a clinical instrument to predict the prognosis of mutation carriers who are close to manifesting HD.

Effect of immersive virtual reality-based cognitive remediation in patients with mood or psychosis spectrum disorders: study protocol for a randomized, controlled, double-blinded trial

BackgroundCognitive impairments are prevalent across mood disorders and psychosis spectrum disorders, but there is a lack of real-life-like cognitive training programmes. Fully immersive virtual reality has the potential to ensure motivating and engaging cognitive training directly relevant to patients’ daily lives. We will examine the effect of a 4-week, intensive virtual reality-based cognitive remediation programme involving daily life challenges on cognition and daily life functioning in patients with mood disorders or psychosis spectrum disorders and explore the neuronal underpinnings of potential treatment efficacy.MethodsThe trial has a randomized, controlled, double-blinded, parallel-group design. We will include 66 symptomatically stable outpatients with mood disorders or psychosis spectrum disorders aged 18–55 years with objective and subjective cognitive impairment. Assessments encompassing a virtual reality test of daily life cognitive skills, neuropsychological testing, measures of daily life functioning, symptom ratings, questionnaires on subjective cognitive complaints, and quality of life are carried out at baseline, after the end of 4 weeks of treatment and at a 3-month follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and at the end of treatment. The primary outcome is a broad cognitive composite score comprising five subtasks on a novel ecologically valid virtual reality test of daily life cognitive functions. Two complete data sets for 54 patients will provide a power of 80% to detect a clinically relevant between-group difference in the primary outcome. Behavioural data will be analysed using linear mixed models in SPSS, while MRI data will be analysed with the FMRIB Expert Analysis Tool (FEAT). Treatment-related changes in neural activity from baseline to end of treatment will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest.DiscussionThe results will provide insight into whether virtual reality-based cognitive remediation has beneficial effects on cognition and functioning in symptomatically stable patients with mood disorders or psychosis spectrum disorders, which can aid future treatment development.Trial registrationClinicalTrials.gov NCT06038955. Registered on September 15, 2023.

Prenatal current-use pesticide exposure and children's neurodevelopment at one year of age in the Infants' Environmental Health (ISA) birth cohort, Costa Rica

BackgroundPesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. ObjectiveWe evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants’ Environmental Health (ISA) birth cohort. MethodsTo determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1–3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). ResultsWe found higher prenatal urinary 2,4-D concentrations were associated with lower language (βper ten-fold increase = −2.0, 95 % confidence interval (CI) = −3.5, −0.5) and motor (βper ten-fold increase = −2.2, 95 %CI = −4.2, −0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (βper ten-fold increase = −1.9, 95 %CI = −4.7, 0.8), and lower motor composite scores among boys (βper ten-fold increase = −3.8, 95 % CI = −7.7, 0.1) but not girls (βper ten-fold increase = 2.3, 95 %CI = −1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. DiscussionPrenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.

Platelet Transfusion and Death or Neurodevelopmental Impairment in Children Born Extremely Preterm

Infants born extremely preterm receive transfusions at higher platelet count thresholds than older children and adults due to concerns for intracranial hemorrhage. A recent randomized trial comparing 2 platelet transfusion thresholds showed the higher threshold was associated with increased risk of long-term adverse neurodevelopmental outcomes. To evaluate the association of platelet transfusion exposure with death and severe neurodevelopmental impairment (NDI) at 2 years' corrected age in a cohort of infants born extremely preterm. An observational cohort study and secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, a randomized, placebo-controlled clinical trial of erythropoietin neuroprotection in neonates born extremely preterm, was conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 819 infants born extremely preterm at 24 to 27 completed weeks of gestation who had a documented outcome (death or neurodevelopmental assessment). Analysis was performed in April 2023. Any platelet transfusion during neonatal intensive care unit hospitalization. The primary composite outcome was death or severe NDI evaluated at 2 years' corrected age using the Bayley Scales of Infant Development-Third Edition (BSID-III) and the Gross Motor Function Classification System and was defined as the presence of severe cerebral palsy or a BSID-III composite motor or cognitive score 2 SDs below the mean. Confounding by indication for platelet transfusion was addressed with covariate adjustment and propensity score methods. Of the 819 infants included in the analysis (429 [52.4%] male; mean [SD] gestational age, 25.5 [1.1] weeks), 245 (30.0%) received at least 1 platelet transfusion during their initial hospitalization. The primary outcome occurred in 46.5% (114 of 245) of infants exposed to a platelet transfusion and 13.9% (80 of 574) of nonexposed infants with a corresponding odds ratio of 2.43 (95% CI, 1.24-4.76), adjusted for propensity score, gestational age at birth, and trial treatment group. The individual components of death and severe NDI were directionally consistent with the overall composite outcome. The findings of this study suggest that platelet transfusion in infants born extremely preterm may be associated with an increased risk of death or severe NDI at 2 years' corrected age, although the possibility of residual confounding by indication cannot be excluded.

Atrophy of the cholinergic regions advances from early to late mild cognitive impairment.

We investigated the volumetric changes in the components of the cholinergic pathway for patients with early mild cognitive impairment (EMCI) and those with late mild cognitive impairment (LMCI). The effect of patients' apolipoprotein 4 (APOE-ε4) allele status on the structural changes were analyzed. Structural magnetic resonance imaging data were collected. Patients' demographic information, plasma data, and validated global cognitive composite scores were included. Relevant features were extracted for constructing machine learning models to differentiate between EMCI (n = 312) and LMCI (n = 541) and predict patients' neurocognitive function. The data were analyzed primarily through one-way analysis of variance and two-way analysis of covariance. Considerable differences were observed in cholinergic structural changes between patients with EMCI and LMCI. Cholinergic atrophy was more prominent in the LMCI cohort than in the EMCI cohort (P < 0.05 family-wise error corrected). APOE-ε4 differentially affected cholinergic atrophy in the LMCI and EMCI cohorts. For LMCI cohort, APOE-ε4 carriers exhibited increased brain atrophy (left amygdala: P = 0.001; right amygdala: P = 0.006, and right Ch123, P = 0.032). EMCI and LCMI patients showed distinctive associations of gray matter volumes in cholinergic regions with executive (R2 = 0.063 and 0.030 for EMCI and LMCI, respectively) and language (R2 = 0.095 and 0.042 for EMCI and LMCI, respectively) function. Our data confirmed significant cholinergic atrophy differences between early and late stages of mild cognitive impairment. The impact of the APOE-ε4 allele on cholinergic atrophy varied between the LMCI and EMCI groups.

Do moderate-to-late preterm twins and singletons differ in the early motor repertoire and later developmental functioning?

Purpose: The aim of this study was to investigate the differences in early motor repertoire and later developmental functioning between moderate-to-late preterm twins and singletons. Material and Methods: The study included 40 moderate-to-late preterm twin infants (50% female), and 40 moderate-to-late preterm singleton infants (50% female). All infants were assessed from 9 up to 20 post-term weeks of corrected age using the General Movement Assessment (GMA), and between 24 and 42 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Results: There were no differences between the Motor Optimality Score (MOS) and its subcategories, including fidgety movements, obtained as a result of detailed GMA (p&gt;0.05), when the early motor repertoire results were examined. At later ages, there were also no significant differences in cognitive, language, and motor domain composite scores between twin and singleton infants, according to Bayley-III (p&gt;0.05). Discussion: Our results suggest moderate-to-late preterm twin infants had a similar developmental process to moderate-to-late preterm singleton infants from early periods up to 3.5 years of age. However, all preterm infants, including moderate-to-late infants, should be assessed in the clinic in terms of the risks of developmental problems from the early period of life.

L-shaped association between dietary zinc intake and cognitive decline in Chinese older people.

The prospective association between dietary zinc (Zn) intake and cognitive decline remains uncertain. We aimed to assess the relationship of dietary Zn intake with the risk of cognitive decline in the Chinese older people, and examine the possible effect modifiers on this association. A total of 3,106 older Chinese adults aged 55years or older from China Health and Nutrition Survey were included. Dietary nutrients intake information was collected by combined 24-h dietary recalls with weighing food inventory. The cognitive decline was defined as the 5-year decline rate in global and composite cognitive scores, based on a subset of items from the Telephone Interview for Cognitive Status-modified. The median follow-up duration was 5.9years. There was an L-shaped association between dietary Zn intake and the 5-year decline rates in global and composite cognitive scores, with an inflection point at 8.8mg/day of dietary Zn. For the composite cognitive scores, compared with the first quantile (<7.9mg/day) of dietary Zn intake, quantiles 2-6 (≥7.9mg/day) had a significantly slower cognitive decline rate (β: -0.24; 95% confidence interval: -0.40 to -0.07). Similar results were found for the global cognitive scores. Moreover, the inverse association between dietary Zn intake and cognitive decline in composite cognitive scores was significantly stronger in those with lower levels of physical activity (P-interactions = 0.041). Dietary Zn intake was negatively associated with cognitive decline in the older people. Maintaining appropriate dietary Zn levels may prevent cognitive decline.

Neurodevelopmental outcomes at 18 months of children diagnosed with CHD compared to children born very preterm.

To compare neurodevelopmental outcomes and parent behaviour ratings of children born term with CHD to children born very preterm. A clinical research sample of 181 children (CHD [n = 81]; very preterm [≤32 weeks; n = 100]) was assessed at 18 months. Children with CHD and born very preterm did not differ on Bayley-III cognitive, language, or motor composite scores, or on expressive or receptive language, or on fine motor scaled scores. Children with CHD had lower ross motor scaled scores compared to children born very preterm (p = 0.047). More children with CHD had impaired scores (<70 SS) on language composite (17%), expressive language (16%), and gross motor (14%) indices compared to children born very preterm (6%; 7%; 3%; ps < 0.05). No group differences were found on behaviours rated by parents on the Child Behaviour Checklist (1.5-5 years) or the proportion of children with scores above the clinical cutoff. English as a first language was associated with higher cognitive (p = 0.004) and language composite scores (p < 0.001). Lower median household income and English as a second language were associated with higher total behaviour problems (ps < 0.05). Children with CHD were more likely to display language and motor impairment compared to children born very preterm at 18 months. Outcomes were associated with language spoken in the home and household income.

Predicting the Progression of Mild Cognitive Impairment to Alzheimer's Dementia Using Recurrent Neural Networks With a Series of Neuropsychological Tests.

The prevalence of Alzheimer's dementia (AD) is increasing as populations age, causing immense suffering for patients, families, and communities. Unfortunately, no treatments for this neurodegenerative disease have been established. Predicting AD is therefore becoming more important, because early diagnosis is the best way to prevent its onset and delay its progression. Mild cognitive impairment (MCI) is the stage between normal cognition and AD, with large variations in its progression. The disease can be effectively managed by accurately predicting the probability of MCI progressing to AD over several years. In this study we used the Alzheimer's Disease Neuroimaging Initiative dataset to predict the progression of MCI to AD over a 3-year period from baseline. We developed and compared various recurrent neural network (RNN) models to determine the predictive effectiveness of four neuropsychological (NP) tests and magnetic resonance imaging (MRI) data at baseline. The experimental results confirmed that the Preclinical Alzheimer's Cognitive Composite score was the most effective of the four NP tests, and that the prediction performance of the NP tests improved over time. Moreover, the gated recurrent unit model exhibited the best performance among the prediction models, with an average area under the receiver operating characteristic curve of 0.916. Timely prediction of progression from MCI to AD can be achieved using a series of NP test results and an RNN, both with and without using the baseline MRI data.

A neuroimaging measure to capture heterogeneous patterns of atrophy in Parkinson’s disease and dementia with Lewy bodies

IntroductionParkinson’s disease (PD) and Dementia with Lewy bodies (DLB) show heterogeneous brain atrophy patterns which group-average analyses fail to capture. Neuroanatomical normative modelling overcomes this by comparing individuals to a large reference cohort. Patient-specific atrophy patterns are measured objectively and summarised to index overall neurodegeneration (the ‘total outlier count’). We aimed to quantify patterns of neurodegenerative dissimilarity in participants with PD and DLB and evaluate the potential clinical relevance of total outlier count by testing its association with key clinical measures in PD and DLB. Materials and methodsWe included 108 participants with PD and 61 with DLB. PD participants were subclassified into high and low visual performers as this has previously been shown to stratify those at increased dementia risk. We generated z-scores from T1w-MRI scans for each participant relative to normative regional cortical thickness and subcortical volumes, modelled in a reference cohort (n = 58,836). Outliers (z < −1.96) were aggregated across 169 brain regions per participant. To measure dissimilarity, individuals’ Hamming distance scores were calculated. We also examined total outlier counts between high versus low visual performance in PD; and PD versus DLB; and tested associations between these and cognition. ResultsThere was significantly greater inter-individual dissimilarity in brain-outlier patterns in PD poor compared to high visual performers (W = 522.5; p < 0.01) and in DLB compared to PD (W = 5649; p < 0.01). PD poor visual performers had significantly greater total outlier counts compared to high (β = -4.73 (SE = 1.30); t = -3.64; p < 0.01) whereas a conventional group-level GLM failed to identify differences. Higher total outlier counts were associated with poorer MoCA (β = -0.55 (SE = 0.27), t = -2.04, p = 0.05) and composite cognitive scores (β = -2.01 (SE = 0.79); t = -2.54; p = 0.02) in DLB, and visuoperception (β = -0.67 (SE = 0.19); t = -3.59; p < 0.01), in PD. ConclusionsNeuroanatomical normative modelling shows promise as a clinically informative technique in PD and DLB, where patterns of atrophy are variable.

Actigraphy estimated sleep moderates the relationship between physical activity and cognition in older adults

Background and aimsPhysical inactivity and poor sleep are common in older adults and may interact to contribute to age- and disease-related cognitive decline. However, prior work regarding the associations among physical activity, sleep, and cognition in older adults is primarily limited to subjective questionnaires that are susceptible to inaccuracies and recall bias. Therefore, this study examined whether objectively measured physical activity and sleep characteristics, each estimated using actigraphy, are independently or interactively associated with cognitive performance. MethodsThe study included 157 older adults free of dementia (136 cognitively unimpaired; 21 MCI; M age = 71.7) from the BIOCARD cohort. ResultsUsing multiple linear regression, cognition was regressed on estimated total volume of physical activity (TVPA), sleep efficiency (SE), wake after sleep onset (WASO), and total sleep time (TST) (adjusted for age, sex, education, diagnosis, vascular risk factors, and Apolipoprotein E (APOE)-e4 genetic status). Models were also run for domain-specific cognitive composite scores. TVPA and SE each were positively associated with a global cognitive composite score. TVPA was positively associated with executive function and language composites, and SE was positively related to executive function, visuospatial, and language composites. Importantly, a TVPA by SE interaction (p = .015) suggested that adults with the poorest SE experienced the greatest benefit from physical activity in relation to global cognition. The other sleep metrics were unrelated to cognitive performance. ConclusionThese results suggest that TVPA and SE may synergistically benefit cognition in older adults.

ASSOCIATIONS OF PLASMA GDF15 WITH PHYSICAL PERFORMANCE AND COGNITIVE FUNCTIONS IN OLDER ADULTS

Abstract Background Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. Methods The study was a secondary analysis on 1096 community-dwelling older adults (aged 69 to 94 years) recruited from the Multidomain Alzheimer’s Preventive Trial. Plasma GDF15 was measured one year after participants’ enrolment. Annual data of physical performance (grip strength and short physical performance battery [SPPB]) and global cognitive functions (mini-mental state examination [MMSE] and a composite cognitive score) were measured for four years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. Results A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = -1.1E-03, 95%CI [-2.0E-03, -1.5E-04]), a lower SPPB score (β = -3.1E-04, 95%CI [-5.4E-04, -9.0E-05]) and worse cognitive functions (β = -2.4E-04, 95%CI [-3.3E-04, -1.6E-04] for composite cognitive score; β = -4.0E-04, 95%CI [-6.4E-04, -1.6E-04] for MMSE). Participants with higher baseline GDF15 demonstrated greater longitudinal declines in SPPB (β = -1.0E-04, 95%CI [-1.7E-04, -2.0E-05]) and composite cognitive score (β = -2.0E-05, 95%CI [-4.0E-05, -3.6E-06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after one year were 2189 pg/mL for SPPB (AUC: 0.580) and 2330 pg/mL for composite cognitive score (AUC: 0.587). Conclusions Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has limited capacity of discriminating older adults who will develop clinically significant functional declines.

LONG-TERM ASSOCIATION OF AN INTENSIVE LIFESTYLE INTERVENTION ON GLOBAL COGNITIVE FUNCTION

Abstract The long-term effects of mid-life changes in lifestyle on later life cognitive function have not been rigorously assessed among individuals with type 2 diabetes. The Look AHEAD Aging study examined differences in standardized composite cognitive function scores in 1367 individuals, currently aged 64 to 95 years, who had enrolled an average of 20 years previously in a randomized controlled trial to compare a 10-year multidomain intensive lifestyle intervention (ILI) to a condition of diabetes support and education (DSE). The composite averaged standardized scores from the telephone administration of tests chosen to capture the individual cognitive domains of memory, attention/processing speed, executive function, and global cognitive function. At enrollment into the Look AHEAD Aging study there was no overall difference between intervention groups in cognitive test scores: mean [SE]: -0.01 [0.03] ILI versus 0.00 [0.04] DSE (p=0.76). However, among participants with overweight at Look AHEAD enrollment, those assigned to ILI had mean [95%CI] of 0.33 [0.08, 0.57] better global cognitive function scores than those assigned to DSE. For those initially with obesity, there was no relative intervention benefit: mean [95%CI] -0.08 [-0.18, 0.03] (interaction p=0.003). Benefits for those with overweight appeared to be strongest for tests of memory. ILI should be recommended to individuals with type 2 diabetes and overweight to provide long-term resilience against cognitive aging. The cognitive benefits we have reported earlier for individuals with overweight during intervention delivery endure for a decade following the cessation of the intervention.

Predicting cognitive decline: Which is more useful, baseline amyloid levels or longitudinal change?

The use of biomarkers for the early detection of Alzheimer’s disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.,2021). However, it is still unclear whether longitudinal Aβ-PET may have additional value for predicting time to cognitive impairment in AD. The current study aims to evaluate the ability of baseline- versus longitudinal rate of change in-11C-Pittsburgh compound B (PiB) Aβ-PET to predict cognitive decline. A cohort of 153 participants who previously underwent PiB-PET scans and comprehensive clinical assessments were used in this study. Our analyses revealed that baseline Aβ is significantly associated with the rate of change in cognitive composite scores, with cognition declining more rapidly when baseline PiB Aβ levels were higher. In contrast, no signification association was identified between the rate of change in PiB-PET Aβ and cognitive decline. Additionally, the ability of the rate of change in the PiB-PET measures to predict cognitive decline was significantly influenced by APOE ε4 carrier status. These results suggest that a single PiB-PET scan is sufficient to predict cognitive decline and that longitudinal measures of Aβ accumulation do not improve the prediction of cognitive decline once someone is amyloid positive.

Financial stress, health and malnourishment among older adults in India

As India’s elderly population grows rapidly, there is a demand for robust policy tools for geriatric health management. This study focuses on unveiling the impact of financial stress and insecurity in diverse economic sectors on adult malnutrition in India. Further, we explore the connections of adult malnourishment with mental and physical health outcomes. Analysis has been done using data of 59,764 respondents aged 45 years and above from the Longitudinal Ageing Study in India (LASI- Wave I) (2017-19). A modified Malnutrition Universal Screening Tool (MUST) has been used to assess the risk of adult malnutrition. It categorizes malnutrition into Low Risk, High Risk Group 1 (HRG1-undernourished), and High Risk Group 2 (HRG2-over-nourished). Approximately 26% of adults were classified in HRG1, characterized by low body mass index, recent hospital admissions, and affiliation with food-insecure households. Around 25% adults belonged to HRG2 characterized by high body mass index and waist-to-hip ratio. The relative risk ratios from the multinomial logit generalized structural equation model indicate that the risk of being in HRG1 was 20–40% higher among respondents not presently working or receiving pension benefits, as well as those involved in agricultural work. The risk of being in HRG2 doubles if the respondent was diagnosed with some chronic disease during the last 12 months. A higher composite cognition score reduces the risk of being in HRG1 by 4%, while it increases the risk of being in HRG2 by 3%. Additionally, experiencing episodic depression raises the risk of being in HRG1 by 10%. Financial insecurity, particularly in the informal and agricultural sectors, coupled with poor mental health, hinders positive nutritional outcomes. Extending universal pro-poor policies to fortify food security in resource poor households and integrating mental health variables in nutrition policies can be beneficial to address adult malnourishment in India.

Association between intermittent hypoxemia and neurodevelopmental outcomes in extremely premature infants: A single-center experience

ObjectiveTo describe the association between intermittent hypoxemic events (IHEs) and severe neurodevelopmental impairment (SNDI) or death in extremely premature infants. Study designRetrospective study of extremely premature infants 230/7–276/7 weeks gestational age (GA) and birthweight (BW) ≤1250 g (g) admitted to a level IV neonatal intensive care unit (NICU) from 2013 to 2017. IHEs, defined as events with SpO2 ≤ 80 % lasting 10 s to 5 min, were algorithmically identified using data extracted from bedside monitors at 2 s intervals (0.5 Hz). The primary outcome was SNDI at 18–24 months corrected age (CA), defined as a Bayley-III motor, language or cognitive composite score ≤69, or death before discharge while the secondary outcome was SNDI alone. We used mixed-effects regression models to evaluate the relationship between mean daily IHE rate per postnatal week of life for the first 12 weeks and the outcomes, and logistic regression models to assess the association between outcomes and summary measures of hypoxic burden for the entire NICU hospitalization. ResultsThe mortality rate was 7 % (18/249) during NICU hospitalization. Of 249 infants born during this time period, IHE and neurodevelopmental outcome data were fully available for 65 infants (mean GA 26 ± 1.4 weeks, mean birth weight (BW) 738 ± 199 g). The outcome of SNDI alone occurred in 34 % (22/65) with a majority demonstrating motor or language delay on the Bayley-III. Although mean daily IHE rate/week was not associated with SNDI or death, total IHE duration was associated with increased odds of SNDI (OR (95 % CI) 1.03 (1.01, 1.05), p = 0.008) in models adjusted for GA. ConclusionsIn a cohort of extremely premature infants 23–27 weeks GA, each hour of total IHE duration (SpO2 ≤ 80 %) was associated with a 2.7 % (0.7 %, 4.8 %) increase in the odds of SNDI at 18–24 months CA.

Postnatal acetaminophen exposure and neurodevelopmental outcomes at 18-21 months corrected gestational age in preterm infants

Studies have reported prenatal acetaminophen exposure is associated with abnormal neurodevelopment. There is limited and conflicting data on neurodevelopmental outcomes following postnatal acetaminophen exposure. Our objective was to investigate the neurodevelopmental outcomes of preterm infants < 29 weeks gestation postnatally exposed to acetaminophen. Retrospective cohort study of infants born between 2008 and 2017 at a tertiary care perinatal center. Exclusion criteria included chromosomal disorders, major congenital abnormalities, and congenital infections. The primary outcome was a composite score of <85 on the cognitive, language, or motor components of the Bayley Scales of Infant and Toddler Development, 3rd edition, assessed at 18 to 21 months corrected gestational age. Multivariate logistic regression was used to assess confounders. Of the 945 infants included in the study, 120 were in the acetaminophen group. There was no difference in any of Bayley-III cognitive, language or motor composite scores of < 85 between the two groups for postnatal acetaminophen exposure, adjusted odds ratios (aORs) 1.03, 95% CI 0.60-1.78, or days of acetaminophen use, aORs 1.10, 95% CI 0.93-1.29. There was no difference in neurodevelopmental outcome between the acetaminophen exposed and non-exposed groups. Our results need validation in larger cohorts. Animal research and cohort studies have suggested that prenatal acetaminophen exposure may be associated with an elevated risk of neurobehavioral abnormalities. However, there is limited and conflicting research on the impact of postnatal acetaminophen on neurodevelopment. The results of this study suggest that postnatal acetaminophen does not negatively impact neurodevelopment at 18 to 21 months in preterm infants born at <29 weeks gestational age. While these results need validation in larger and more longitudinal studies, this study provides reassurance for the use of postnatal acetaminophen in extremely preterm infants.

Clinical Manifestations.

In Alzheimer's disease (AD), a long preclinical and prodromal period precedes dementia onset in which cognition declines slowly, but at variable rates for different domains. Positive AD biomarkers, (e.g., amyloid, Tau, or APOE ε4 carriage), increase rates of cognitive decline and transition to dementia. However, the extent to which cognitive decline, identified in some older adults, reflects neurodegenerative disease or normal aging in the absence of knowledge about biomarkers or genes is not well understood. We applied a novel approach to classify cognitive decline in individuals using six cognitive composite scores (AIBL Pre-clinical Alzheimer's Cognitive Composite (AIBL-PACC), episodic recall, attention, executive function, language and recognition). We examine group-wise differences across cognitive composite scores and assessed frequencies for AD biomarker positivity amongst the novel groups. Prospective data from 1,389 Cognitively unimpaired (CU) participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing were analysed using an unsupervised multivariate mixture modelling framework, accounting for age, gender and APOE ε4 allele status. Participants cognitive status was classified for their final visit. The cognitive profile and biomarker characteristics of adults with abnormal cognitive decline was compared. Differences in composite score values between cognitive decline and no decline groups were strongest for episodic recall (Cohen's d = 1.49) and the AIBL-PACC score (Cohen's d = 1.45, Table 1, Figure 1A). By comparison, differences in composite scores between Aβ-PET groups, or APOE ε4 allele carriers/non-carriers were of less magnitude (Table 1, Figure 1). Participants with cognitive decline were more likely to be amyloid positive, (decline: 42% vs no decline: 28%, p<0.0001), but not ε4 allele carriers (decline: 28% VS no decline: 27%, p>0.05). A measure of objective cognitive decline, created using flexible mixture models with six cognitive composite scores from AIBL, has utility for discerning participants with early changes in cognition. Based upon using the cognitive data alone, this method was able to detect amyloid positivity in those CU participants with cognitive decline.