Cognitive Impairment In Old Age Research Articles

Cognitive Rehabilitation Programme (CRP): An Effective Tool Against Mild Cognitive Impairment Among Elderly

Background: With a steady increase in life expectancy seen worldwide, age-associated cognitive decline and mild cognitive impairment in old age are major public health challenges. Objective: To determine the effectiveness of the Cognitive Rehabilitation Program on cognition parameters in old age people with mild cognitive impairment. Materials and Methods: Design: This study was a quasi-experimental design using a non-equivalent control group pretest post-test design. Setting/Location: Mullana and Adhoya villages of Ambala, Haryana. Subjects: Eighty old age people with mild cognitive impairment. Intervention: The pre- and post-interventional cognition parameters were assessed using Addenbrooke’s cognitive examination on Day 1 and Day 29. The cognitive Rehabilitation Program was administered in the experimental group once a day for 28 days. Outcome Measures: Dependent variables were cognition parameters. Results and Conclusion: In the experimental group, a significant increase in cognition parameters score was observed from Day 1 (62.28 ± 6.23) to Day 29 (63.25 ± 5.10) after administration of the Cognitive Rehabilitation Program. In the comparison group, there was a non-significant decrease in cognition parameters score from Day 1 (56.73 ± 8.24) to Day 29 (55.85 ± 8.90). The post-implementation cognition parameters score of old age people in the experimental group (mean = 63.25) was significantly higher than in the comparison group (mean = 55.85). The mean gain in cognition scores was significantly higher in the experimental group than in the comparison group with a moderate effect size. It is concluded that the cognitive rehabilitation program is an effective tool in improving cognition parameters score among old age people with mild cognitive impairment.

The relationship between playing musical instruments and cognitive trajectories: Analysis from a UK ageing cohort.

The accumulation of age-associated cognitive deficits can lead to Mild Cognitive Impairment (MCI) and dementia. This is a major public health issue for the modern ageing population, as it impairs health, independence and overall quality of life. Keeping the brain active during life has been associated with an increased cognitive reserve, therefore reducing the risk of cognitive impairment in older age. Previous research has identified a potential relationship between musicality and cognition. Explore the relationship between musicality and cognitive function in a large cohort of older adults. This was a nested study within the PROTECT-UK cohort, which collects longitudinal computerised assessments of cognitive function in adults over 40. Participants were invited to complete the validated Edinburgh Lifetime Musical Experience Questionnaire (ELMEQ) to assess their musical experience and lifetime exposure to music. Linear regression analysis was performed using cognitive data from PROTECT-UK. Analysis identified an association between musicality and cognition in this cohort. Playing a musical instrument was associated with significantly better performance in working memory and executive function. Significant associations were also found between singing and executive function, and between overall musical ability and working memory. Our findings confirm previous literature, highlighting the potential value of education and engagement in musical activities throughout life as a means of harnessing cognitive reserve as part of a protective lifestyle for brain health.

Comorbidity of cerebral amyloid angiopathy and Alzheimer's disease. Clinical case analysis

The development of cognitive impairment in old age is often caused by overlapping neurodegenerative and cerebrovascular changes which have a mutually aggravating clinical effect. In recent years, the problem of cerebral amyloid angiopathy (CAA), which is one of the variants of such an interaction, has gained importance. Despite the frequent occurrence of this pathology in the elderly, a unified approach to the treatment of these patients has not yet been developed, especially taking into account the frequent combination with other nosological forms. CAA is a disease associated with both Alzheimer's type neurodegeneration and cerebrovascular pathology. The article presents a clinical case illustrating this situation and discusses the diagnostic algorithm in detail. The characteristics of the pathogenesis and clinical manifestations of CAA and the link between neurodegenerative and cerebrovascular pathologies are discussed.

Long-term environmental enrichment overcomes depression, learning, and memory impairment in elderly CD-1 mice with maternal sleep deprivation exposure.

Early-life stress disrupts central nervous system development and increases the risk of neuropsychiatric disorder in offspring based on rodent studies. Maternal sleep deprivation (MSD) in rodents has also been associated with depression and cognitive decline in adult offspring. However, it is not known whether these issues persist into old age. Environmental enrichment is a non-pharmacological intervention with proven benefits in improving depression and cognitive impairment; however, it is unclear whether these benefits hold for aging mice following MSD exposure. The aim of this study was to explore the effects of MSD on depression and cognition in elderly offspring CD-1 mice and to determine whether long-term environmental enrichment could alleviate these effects by improving neuroinflammation and synaptic plasticity. The offspring mice subjected to MSD were randomly assigned to either a standard environment or an enriched environment. At 18 months of age, the forced swimming and tail suspension tests were used to evaluated depression-like behaviors, and the Morris water maze test was used to evaluate cognitive function. The expression levels of hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins were also measured. MSD increased depression-like behaviors and impaired cognition function in aging CD-1 offspring mice. These effects were accompanied by upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-α expression, and downregulated brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin expression in the hippocampus. All of these changes were reversed by long-term exposure to an enriched environment. These findings suggest that MSD exerts long-term effects on the behaviors of offspring in mice, leading to depression and cognitive impairment in older age. Importantly, long-term environmental enrichment could counteract the behavior difficulties induced by MSD through improving hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins.

Correlation between serum lipid profiles and cognitive impairment in old age: a cross-sectional study

BackgroundThe correlation between cognitive function and lipid profiles, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, is inconsistent.AimsThis cross-sectional study investigated the association between serum...

Creativity across the lifespan: changes with age and with dementia

BackgroundIt is well known that older age is associated with losses in cognitive functioning. Less is known about the extent to which creativity is changing with age or dementia. Aim of the current study was to gain more insights into psychometric aspects of creativity in younger and older people as well as people with dementia.MethodOur sample comprised three groups, (1) participants between age 18—30 years (n = 24), (2) participants 65 + years without cognitive impairment (n = 24), and (3) participants 65 + years with cognitive impairment / dementia (n = 23). Cognitive abilities were assessed via the Standard Progressive Matrices Test (SPM), Montreal Cognitive Assessment Test (MoCa), and Trail Making Test (TMT). Creativity was assessed via the Creative Reasoning Task (CRT), Test of Creative Thinking-Drawing Production (TCT-DP), and Alternate Uses Task (AUT).ResultsCompared to younger people, older people scored significantly lower in only two out of eleven creativity sub-scores (one in the CRT and one in the TCT-DP). Performance in the SPM was significantly associated with these two sub-scores and age. Cognitively impaired older people had significantly lower scores in the creativity task AUT compared to cognitively healthy older people and younger people. The associations between MoCa and AUT scores were also significant.ConclusionCreativity appears relatively stable in older age, with exception of those creativity skills that are affected by abstract reasoning (SPM), which appear susceptible to aging. As our findings suggest, cognitive impairment in older age might impair only some aspects of creativity with other creativity aspects being comparable to cognitively healthy people. The age-related and the cognitive status-related effects seem to be independent. The preserved creative abilities can be used in dementia care programs.

Purpose in life promotes resilience to age-related brain burden in middle-aged adults

BackgroundDisease-modifying agents to counteract cognitive impairment in older age remain elusive. Hence, identifying modifiable factors promoting resilience, as the capacity of the brain to maintain cognition and function with aging and disease, is paramount. In Alzheimer’s disease (AD), education and occupation are typical cognitive reserve proxies. However, the importance of psychological factors is being increasingly recognized, as their operating biological mechanisms are elucidated. Purpose in life (PiL), one of the pillars of psychological well-being, has previously been found to reduce the deleterious effects of AD-related pathological changes on cognition. However, whether PiL operates as a resilience factor in middle-aged individuals and what are the underlying neural mechanisms remain unknown.MethodsData was obtained from 624 middle-aged adults (mean age 53.71 ± 6.9; 303 women) from the Barcelona Brain Health Initiative cohort. Individuals with lower (LP; N = 146) and higher (HP; N = 100) PiL rates, according to the division of this variable into quintiles, were compared in terms of cognitive status, a measure reflecting brain burden (white matter lesions; WMLs), and resting-state functional connectivity, examining system segregation (SyS) parameters using 14 common brain circuits.ResultsNeuropsychological status and WMLs burden did not differ between the PiL groups. However, in the LP group, greater WMLs entailed a negative impact on executive functions. Subjects in the HP group showed lower SyS of the dorsal default-mode network (dDMN), indicating lesser segregation of this network from other brain circuits. Specifically, HP individuals had greater inter-network connectivity between specific dDMN nodes, including the frontal cortex, the hippocampal formation, the midcingulate region, and the rest of the brain. Greater functional connectivity in some of these nodes positively correlated with cognitive performance.ConclusionExpanding previous findings on AD pathology and advanced age, the present results suggest that higher rates of PiL may promote resilience against brain changes already observable in middle age. Furthermore, having a purposeful life implies larger functional integration of the dDMN, which may potentially reflect greater brain reserve associated to better cognitive function.

Genetic risk for attention‐deficit/hyperactivity disorder is associated with amyloid‐dependent cognitive decline in older adults

AbstractBackgroundRecent epidemiological studies using population‐based registers showed that patients with Attention‐Deficit/Hyperactivity Disorder (ADHD) are more likely to be diagnosed with mild cognitive impairment (MCI) and Alzheimer’s disease (AD), suggesting a higher risk for cognitive impairment in older age. Here, we aimed to assess whether genetic liability for ADHD, as measured by a validated polygenic risk score (ADHD‐PRS), is associated with cognitive decline in cognitively unimpaired (CU) subjects and whether these effects vary according to baseline amyloid‐β (Aβ) burden.MethodWe studied 212 CU participants (116 women [54.7%], mean [SD] age of 73.1 [5.9]) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Subjects had available baseline Aβ burden (measured by [18F]Florbetapir Aβ‐PET) and genetic information, as well as a minimum of 2 cognitive assessments (Preclinical Alzheimer Cognitive Composite [PACC] and MMSE) in a 6‐year period. Aβ positivity was defined using a previously published cutoff of global [18F]Florbetapir PET SUVR > 1.11. We calculated ADHD‐PRS using data from the latest genome‐wide association study on ADHD, with a p‐value threshold of 1. Statistical analyses were performed using linear mixed‐effects models adjusted for age, sex, APOE ε4 status, and the first seven principal components to adjust for population stratification.ResultADHD‐PRS was normally distributed and was not associated with age, sex, or APOE ε4 status (Figure 1). We observed a significant ADHD‐PRS by time interaction (β=‐.03, 95% CI ‐.05 to ‐.01, p‐value=.001 for PACC, β=‐.04, 95% CI ‐.07 to ‐.009, p‐value=.01 for MMSE) on cognitive performance, indicating that higher ADHD‐PRS is associated with decreased cognitive function over time (Figure 2). Additionally, we observed a significant interaction between ADHD‐PRS, time, and baseline Aβ burden (β=‐.05, 95% CI ‐.10 to ‐.008, p‐value=.02 for PACC, β=‐.08, 95% CI ‐.15 to ‐.01, p‐value=.02 for MMSE), suggesting that higher ADHD‐PRS is associated with longitudinal cognitive decline only in Aβ‐positive individuals (Figure 3).ConclusionOur findings indicate that higher genetic liability for ADHD is associated with cognitive decline in Aβ‐positive older adults without cognitive impairment. These findings support the hypothesis that higher rates of MCI and AD in patients with ADHD may result from decreased resilience to Aβ pathology.

Multiple exposures to sevoflurane across postnatal development may cause cognitive deficits in older age.

The aim of the study was to determine the effects of repeated anesthesia exposure across postnatal development. Seventy-two newborn Sprague-Dawley rats were randomly divided into Sev group and Con-aged group. Sev groups were exposed to 2.6% sevoflurane for 2 h on postnatal day (P) 7, P14, and P21; the Con groups only received carrier gas for 2 h. Learning and memory were evaluated using the MWM test at P31 (juvenile), P91 (adult), and 18 months postnatally (aged). The relative expression of APP and Mapt mRNA was detected by RT-PCR, while Aβ, tau, and P-tau protein levels were analyzed by immunohistochemistry. After repeated inhalation of sevoflurane, MWM test performance was significantly decreased in the Sev-aged group compared to the Con-aged group (P > 0.05). The relative expression of APP and Mapt mRNA was not significantly different between groups in each growth period (P > 0.05). The tau expression in the juvenile hippocampal CA1, CA3, and dentate gyrus regions increased markedly in the Sev group, while P-tau only increased in the hippocampal CA3 region in the Sev-adult group. The expression of tau, P-tau, and Aβ in the hippocampal regions was upregulated in the Sev-aged group. Multiple exposures to sevoflurane across postnatal development can induce or aggravate cognitive impairment in old age. Whether multiple sevoflurane exposures across postnatal development cause cognitive impairment in childhood, adulthood, or old age, as well as the relationship between sevoflurane and the hippocampal Aβ, tau, and P-tau proteins, remains unknown. This study's results demonstrate that multiple exposures to sevoflurane across postnatal development do not appear to affect cognitive function in childhood and adulthood; however, multiple exposures may lead to a cognitive function deficit in old age. The underlying mechanism may involve overexpression of the tau, P-tau, and Aβ proteins in the hippocampus.

Leisure activities and cognitive impairment in old age: The role of life course socioeconomic status

Objectives: In the current literature on cognitive function, life course socioeconomic status (SES) and engaging in leisure activities are often viewed as parallel measures of cognitive reserve that independently affect cognitive impairment in old age. Some studies also suggest that leisure activity mediates the effect of SES on cognitive impairment. What is less examined is the modification effect of SES on the association between engaging in leisure activities and cognitive impairment, especially from a life course perspective. In this study, we focus on the interaction effects of specific measures of SES and leisure activities on cognitive impairment. Method: We use data from the Chinese Longitudinal Healthy Longevity Survey, which includes five waves of interviews with adults aged 65 and older between 2002 and 2014. Cognitive impairment is measured by the Chinese version of the Mini-Mental Status Examination. Childhood and adulthood SES and participation in seven leisure activities are included in this analysis. We adopt a lagged independent variable approach and the Generalized Linear Mixed Model to conduct the analysis. Results: Findings confirm that higher SES in both childhood and adulthood are associated with low levels of cognitive impairment in the older Chinese population. Furthermore, there are significant interaction effects between specific life course SES and leisure activities with a consistent pattern: Those of higher life course SES enjoy extra benefits from engaging in leisure activities. Conclusion: The findings point to a modification mechanism that connects life course SES, leisure activities, and cognitive health inequality among older adults.

Cognitive impairment in elderly patients suffering from Alzheimer's disease

The purpose of the study: to study destructive forms of cognitive impairment in old age. Materials and methods. A study of 38 people was conducted, of which 16 were men and 22 were women. The control sample consists of 23 people, of which 8 are men and 15 are women. The definition of the control sample was based on the fact that this category of people had cognitive impairments that are the result of other age-related changes that are not the result of AD, whereas the experimental sample needed to have cognitive impairments that are the result of AD. The experimental sample consisted of 15 people, 7 men, 8 women. In the process of MMSE testing, 6 subjects (15.8%) entered the first group, 10 subjects (26.3%) entered the second group, and 22 (57.9%) entered the last group. 42.1% of respondents had mild Alzheimer's type dementia, while 57.9% of respondents had cognitive impairment due to age-related changes. According to the indicators obtained by the method of the short scale of assessment of mental status (Mini-Mental State Examination, MMSE), it can be concluded that memory, attention and orientation in time and space are primarily reduced. Data on the Frontal Dysfunction Battery (FAB) technique showed the absence of a grasping reflex in 29 out of 38 subjects (76.3%), so the presence of a grasping reflex most often indicates a severe degree of Alzheimer's type dementia.

The Interaction of Life Course Socioeconomic Status and Leisure Activities on Cognitive Performance in Old Age

While the separate effects of socioeconomic status and engaging in leisure activities on cognition have been well documented, their interaction effect has rarely been examined. After examining life course socioeconomic status (SES) on cognitive impairment in old age, this paper is focused on exploring the interaction effects between life course SES and leisure activities. We use data from the Chinese Longitudinal Healthy Longevity Survey, which covers five waves of interviews of adults aged 65 or older between 2002 and 2014. Cognitive impairment is measured by the Chinese version of Mini-Mental Status Examination. Two sets of variables are used to reflect an older person’s life course SES in childhood and adulthood, respectively. Seven leisure activities are included in this analysis. We adopt the lagged independent variable approach and a Generalized Linear Mixed Model to examine the association between leisure activity and cognitive impairment over time. Results show that there is an independent impact of SES in both childhood and adulthood on cognitive decline in Chinese older population. Furthermore, as the focus of this study, there are substantial interactions between life course SES and engaging in leisure activities with a consistent pattern: those of higher life course SES enjoy extra benefits from engaging in leisure activities. The interactions between life course SES and leisure activities promise a competing approach accounting for cognitive health inequality among older adults.

Circulating Mediators of Apoptosis and Inflammation in Aging; Physical Exercise Intervention.

Sarcopenia is an age-related loss of skeletal muscle mass caused by many cellular mechanisms and also by lifestyle factors such as low daily physical activity. In addition, it has been shown that sarcopenia may be associated with inflammation and cognitive impairment in old age. Regular exercise is key in reducing inflammation and preventing sarcopenia and diseases related to cognitive impairment. The study was designed to assess the impact of exercise training on circulating apoptotic and inflammatory markers of sarcopenia in older adults. Eighty older adults aged 70.5 ± 5.8 years were randomized to the physically active group who participated in a 10-month Tai-Chi training session (TC, n = 40) and the control group who participated in health education sessions (HE, n = 40). Tai-Chi training caused a significant decrease in fat mass (FM) by 3.02 ± 3.99%, but an increase in appendicular skeletal muscle mass index (ASMI) by 1.76 ± 3.17% and gait speed by 9.07 ± 11.45%. Tai-Chi training elevated the plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNFα), and tumor necrosis receptor factor II (TNFRII), and decreased caspases 8 and 9. Despite the increase in TNFα, apoptosis was not initiated, i.e., the cell-free DNA level did not change in the TC group. The study demonstrated that Tai-Chi training significantly reduced the symptoms of sarcopenia through the changes in body composition and physical performance, and improvements in cytokine-related mechanisms of apoptosis.

Childhood Socioeconomic Status, Adult Personality, and Cognition: Early Indicators of Cognitive Impairment in Old Age

This study investigated the association between childhood socioeconomic status (cSES) risk of cognitive impairment but not dementia (CIND), cognitive impairment (dementia or CIND), and dementia and whether adult personality mediated this association. A sample of 10,289 participants (aged 50 and older) from the Health and Retirement Study (HRS) were followed across 2-year periods between 2006 - 2018. Estimates of mediation effects in Cox Proportional Hazards regressions were conducted using Mplus software to approximate the total effects of cSES on the cognitive outcomes and the natural indirect effects and natural direct effects derived when personality causally mediated this outcome. cSES was associated with increased risk of all three cognitive outcomes. Conscientiousness partially mediated the relationship between cSES and dementia, CIND, and cognitive impairment risk while neuroticism partially mediated dementia and impairment, but not CIND. Personality improved the overall model fit between cSES and both CIND and impairment, and conscientiousness was specifically associated with significantly lowered cognitive impairment risk over time. Conscientiousness and neuroticism substantially mediated the relationship between cSES and risk of impairment in old age. This research adds to lifespan models and suggests that distinct personality traits attenuate early childhood factors that contribute to lifespan development and cognitive aging. Conscientiousness in particular may act as a protective buffer mediating risk factors associated with cognitive impairment in old age.

Patterns of Mitochondrial TSPO Binding in Cerebral Small Vessel Disease: An in vivo PET Study With Neuropathological Comparison.

Small vessel disease (SVD) is associated with cognitive impairment in older age and be implicated in vascular dementia. Post-mortem studies show proliferation of activated microglia in the affected white matter. However, the role of inflammation in SVD pathogenesis is incompletely understood and better biomarkers are needed. We hypothesized that expression of the 18 kDa translocator protein (TSPO), a marker of microglial activation, would be higher in SVD. Positron emission tomography (PET) was performed with the second-generation TSPO ligand [11C]PBR28 in 11 participants with SVD. TSPO binding was evaluated by a two-tissue compartment model, with and without a vascular binding component, in white matter hyperintensities (WMH) and normal-appearing white matter (NAWM). In post-mortem tissue, in a separate cohort of individuals with SVD, immunohistochemistry was performed for TSPO and a pan-microglial marker Iba1. Kinetic modeling showed reduced tracer volume and blood volume fraction in WMH compared with NAWM, but a significant increase in vascular binding. Vascular [11C]PBR28 binding was also increased compared with normal-appearing white matter of healthy participants free of SVD. Immunohistochemistry showed a diffuse increase in microglial staining (with Iba1) in sampled tissue in SVD compared with control samples, but with only a subset of microglia staining positively for TSPO. Intense TSPO staining was observed in the vicinity of damaged small blood vessels, which included perivascular macrophages. The results suggest an altered phenotype of activated microglia, with reduced TSPO expression, in the areas of greatest white matter ischemia in SVD, with implications for the interpretation of TSPO PET studies in older individuals or those with vascular risk factors.

Metformin administration during pregnancy attenuated the long-term maternal metabolic and cognitive impairments in a mouse model of gestational diabetes.

Background: Gestational diabetes mellitus (GDM) is a metabolic disease that can have long-term adverse effects on the cognitive function of mothers. In our study, we explored the changes in metabolic health and cognitive function in mice of middle- and old- age after exposure to GDM, and whether metformin therapy during pregnancy provided long-term benefits.Results: Mice with GDM demonstrated significant cognitive impairment in old age, which was associated with insulin resistance. Gestational metformin therapy was shown to increase insulin sensitivity and improve cognition. The ovarian aging rate was also accelerated in mice exposed to GDM during pregnancy, which may be related to fatty acid metabolism in the ovaries.Conclusion: Treatment with metformin during pregnancy was shown to improve fatty acid metabolism in ovarian tissues.Method: During pregnancy, mice were fed with a high-fat diet (GDM group) or a low-fat diet (Control group), and a third group received metformin while receiving a high-fat diet (Treatment group). At 12 months old, the mice completed an oral glucose tolerance test, insulin tolerance test, Morris water maze test, female sex hormones were measured, and metabolite profiles of tissue from the ovaries, hypothalamus, and pituitary glands were analysed using gas chromatography-mass spectrometry.

Cognitive Impairment in Old Age

Abstract. A decline in cognitive functioning is part of physiological aging. Accelerated cognitive decline is frequently linked to pathological changes, mostly due to Alzheimer’s Disease (AD), but is present also in Mild Cognitive Impairment (MCI) which is a predictor of transition to dementia. This review aims to summarize possible preventive biological and psychological treatments in different stages of lifespan to avoid more rapid cognitive decline and prevent pathological aging. Psychophysiological approaches aim to prevent brain damage and inflammation, two factors playing probably a major role in middle and old age. Interventions on working memory and imagery, using “cognitive reserve,” are beneficial for tolerating neuropathological age-related changes. Some controversial results are outlined, suggesting explanations for the inconsistency of findings. Although clear evidence from interventional studies is lacking, it seems that multi-domain interventions should be recommended to avoid or delay cognitive decline.

Adiposity, Weight Change, and Risk of Cognitive Impairment: The Singapore Chinese Health Study.

Few prospective studies with long duration of follow-up have assessed the relations of body mass index (BMI) and weight change with cognitive function, especially in Asian populations. To investigate whether BMI and weight change in midlife are associated with cognitive impairment in old age. We used data from 14,691 participants in the Singapore Chinese Health Study and computed weight change as the difference between weight reported at baseline (1993-1998) at mean age of 53.0 years and follow-up 1 (1999-2004) at mean age of 58.6 years. Cognitive impairment was determined using education-specific cut-offs of the Singapore Modified Mini-Mental State Examination at follow-up 3 (2014-2016) at mean age of 72.9 years. We used multivariable logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations. Obesity (as defined BMI ≥27.5 kg/m2) was associated with a higher risk of cognitive impairment at baseline (OR 1.33, 95% CI 1.12-1.58) and follow-up 1 (OR 1.30, 95% CI 1.10-1.54) compared to BMI of 18.5-22.9 kg/m2. Underweight (BMI <18.5 kg/m2) was not associated with a significant risk either at baseline (OR 0.91, 95% CI 0.73-1.13) or follow-up 1 (OR 1.05, 95% CI 0.85-1.28). Compared to participants with <5% weight change, the ORs (95% CIs) of cognitive impairment were 1.20 (1.03-1.41) for those with 5-9.9% weight loss, 1.53 (1.29-1.81) for ≥10% weight loss, 1.00 (0.85-1.17) for 5-9.9% weight gain, and 1.50 (1.28-1.75) for ≥10% weight gain. Obesity, weight loss, and excessive weight gain at midlife were associated with an increased risk of cognitive impairment at old age.

The effect of mid-life insulin resistance and type 2 diabetes on older-age cognitive state: the explanatory role of early-life advantage

Aims/hypothesisType 2 diabetes, hyperglycaemia and insulin resistance are associated with cognitive impairment and dementia, but causal inference studies using Mendelian randomisation do not confirm this. We hypothesised that early-life cognition and social/educational advantage may confound the relationship.MethodsFrom the population-based British 1946 birth cohort, a maximum number of 1780 participants had metabolic variables (type 2 diabetes, insulin resistance [HOMA2-IR] and HbA1c) assessed at age 60–64 years, and cognitive state (Addenbrooke’s Cognitive Examination III [ACE-III]) and verbal memory assessed at age 69 years. Earlier-life measures included socioeconomic position (SEP), cognition at age 8 years and educational attainment. Polygenic risk scores (PRSs) for type 2 diabetes were calculated. We first used a PRS approach with multivariable linear regression to estimate associations between PRSs and metabolic traits and later-life cognitive state. Second, using a path model approach, we estimated the interrelationships between earlier-life measures, features of mid-life type 2 diabetes and cognitive state at age 69 years. All models were adjusted for sex.ResultsThe externally weighted PRS for type 2 diabetes was associated with mid-life metabolic traits (e.g. HOMA2-IR β = 0.08 [95% CI 0.02, 0.16]), but not with ACE-III (β = 0.04 [−0.02, 0.90]) or other cognitive outcomes. While there was an association between HOMA2-IR and subsequent ACE-III (β = −0.09 [−0.15, −0.03]), path modelling showed no direct effect (β = −0.01 [−0.06, 0.03]) after accounting for the association between childhood SEP and education with HOMA2-IR. The same pattern was observed for later-life verbal memory.Conclusions/interpretationAssociations between type 2 diabetes and mid-life metabolic traits with subsequent cognitive state do not appear causal, and instead they may be explained by SEP in early life, childhood cognition and educational attainment. Therefore, glucose-lowering medication may be unlikely to combat cognitive impairment in older age.

Meat consumption in midlife and risk of cognitive impairment in old age: the Singapore Chinese Health Study.

Epidemiological studies directly investigating the association between different types of meat intake and cognitive impairment are limited. We, therefore, examined this association in the Singapore Chinese Health Study. In total, 16,948 participants were included in analysis. Diet was measured by a 165-item semiquantitative food-frequency questionnaire at baseline (1993-1998) when participants were 45-74years. Cognitive impairment was defined using a Singaporemodified version of Mini-Mental State Examination during follow-up three visits (2014-2016) when participants were 61-96years. Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI). Cognitive impairment was present in 2443 (14.4%) participants. Compared to the lowest quartile, the highest quartile of red meat intake was associated with increased risk of cognitive impairment (OR 1.16, 95% CI 1.01-1.32, P for trend = 0.009), while the corresponding value for poultry intake was 0.89 (95% CI 0.78-1.02, P for trend = 0.10). Higher fresh fish/shellfish was associated with a lower risk of cognitive impairment (OR 0.88, 95% CI 0.77-1.00, P for trend = 0.03), while preserved fish/shellfish intake was associated with a higher risk (OR 1.19, 95% CI 1.04-1.36, P for trend = 0.01). This study found that a higher intake of red meat in midlife was associated with increased likelihood of cognitive impairment in later life, while substitution of red meat intake with poultry or fresh fish/shellfish was associated with reduced risk.