Cognition In Middle-aged Adults Research Articles

The Mediterranean diet is not associated with neuroimaging or cognition in middle-aged adults: a cross-sectional analysis of the PREVENT dementia programme.

The Mediterranean diet (MedDiet) has been associated with reduced dementia incidence in several studies. It is important to understand if diet is associated with brain health in midlife, when Alzheimer's disease and related dementias are known to begin. This study used data from the PREVENT dementia programme. Three MedDiet scores were created (the Pyramid, Mediterranean Diet Adherence Screener [MEDAS] and MEDAS continuous) from a self-reported food frequency questionnaire. Primary outcomes were hippocampal volume and cube-transformed white matter hyperintensity volume. Secondary outcomes included cornu ammonis 1 and subiculum hippocampal subfield volumes, cortical thickness and measures of cognition. Sex-stratified analyses were run to explore differential associations between diet and brain health by sex. An exploratory path analysis was conducted to study if any associations between diet and brain health were mediated by cardiovascular risk factors for dementia. In all, 504 participants were included in this analysis, with a mean Pyramid score of 8.10 (SD 1.56). There were no significant associations between any MedDiet scoring method and any of the primary or secondary outcomes. There were no differences by sex in any analyses and no significant mediation between the Pyramid score and global cognition by cardiovascular risk factors. Overall, this study did not find evidence for an association between the MedDiet and either neuroimaging or cognition in a midlife population study. Future work should investigate associations between the MedDiet and Alzheimer's disease and related dementias biomarkers as well as functional neuroimaging in a midlife population.

The Influence of Cholesterol on Resting Brain Blood Flow and Cognition in Middle-Aged Adults

Total cholesterol increases with age, with peak values observed in middle-aged adults (50-64 years old). Middle-aged adults are vulnerable to experiencing future cognitive decline, in which the concurrent reductions in resting brain blood flow with aging have been linked to cognitive impairments. PURPOSE: To determine the influence of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol on resting brain blood flow and cognition in middle-aged adults (50-64 years old). Methods: LDL and HDL cholesterol were measured in 18 healthy adults (57 ± 4 years old). Resting cerebral and hippocampal blood flow were assessed using a pseudo-continuous arterial spin labeling (pCASL) sequence from the Human Connectome Project inside a Siemens Prisma 3T MRI scanner. Cognitive function was assessed using the Hopkins Verbal Learning Test (HVLT) and the National Institute of Health (NIH) Toolbox’s Flanker Inhibitory Control and Attention Test and Pattern Comparison Processing Speed Test. The influence of cholesterol on resting brain blood flow and cognition was analyzed using Pearson correlations. Results: LDL cholesterol (123 ± 23 mg/dL) was negatively correlated with resting cerebral (70.1 ± 12.5 ml.100g−1.min−1; r = -0.78, p = 0.0001) and hippocampal (67.6 ± 13.1 ml.100g−1.min−1; r = -0.74, p = 0.0005) blood flow. There were no significant associations for HDL cholesterol (67 ± 17 mg/dL) on resting cerebral (r = -0.03, p = 0.9) nor hippocampal (r = -0.04, p = 0.9) blood flow. Among the cognitive function tests, only hippocampal-dependent memory retention from the HVLT was positively associated with HDL cholesterol (r = 0.51, p = 0.03). A follow-up analysis revealed participants with a higher resting brain blood flow presented a tendency for higher scores in the Pattern Comparison Processing Speed Test (r = 0.44, p = 0.06). CONCLUSION: LDL cholesterol, a cardiometabolic risk factor, was negatively associated with resting cerebral and hippocampal blood flow whereas the potentially cardioprotective factor HDL cholesterol was not. HDL cholesterol was positively associated with memory-related outcomes. Our results suggest cholesterol may impact resting brain blood flow and should be considered a target in preventing or delaying age-related memory loss. Further data are required to elucidate the underlying mechanisms. SIGNIFANCE: The cardiometabolic effects of cholesterol may have additional implications on cerebrovascular and brain health. NIH/NIGMS - P20 GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Insulin resistance, age and depression’s impact on cognition in middle-aged adults from the PREVENT cohort

BackgroundAlzheimer’s disease (AD), type 2 diabetes mellitus (characterised by insulin resistance) and depression are significant challenges facing public health. Research has demonstrated common comorbidities among these three conditions, typically focusing...

Sense of Coherence Mediates the Relationship Between Cognitive Reserve and Cognition in Middle-Aged Adults.

In recent years, supported by new scientific evidence, the conceptualization of cognitive reserve (CR) has been progressively enriched and now encompasses not only cognitive stimulating activities or educational level, but also lifestyle activities, such as leisure physical activity and socialization. In this context, there is increasing interest in understanding the role of psychological factors in brain health and cognitive functioning. In a previous study, we have found that these factors mediated the relationship between CR and self-reported cognitive functioning. In this study, we have confirmed an association between two important constructs included in the psychological wellbeing and salutogenic models, “purpose in life” and “sense of coherence,” CR, as assessed using a questionnaire, and cognitive functioning, as evaluated using a comprehensive neuropsychological battery. Results from 888 middle-aged healthy participants from the Barcelona Brain Health Initiative indicate that both sense of coherence (SoC) and CR were positively associated with verbal memory, reasoning and attention, working memory, and global cognition. Moreover, the relation between CR and cognitive functioning in the different domains is partially mediated by SoC. When we controlled for brain integrity, introducing into the model neurofilament light chain measures, the mediator role of SoC was confirmed for reasoning and attention and global cognition. However, purpose in life was not associated with cognitive functioning. These results reveal the central role of the SoC construct, which mediates the association between classic CR estimates and cognitive functions, potentially representing a modifiable target for interventions that aim to promote brain health.

Current and long‐term trajectories of high BMI are associated with poorer cognitive functioning in middle‐aged adults at high Alzheimer’s risk due to a maternal family history

The deleterious impact of adiposity on cognition in older adults is well-established. Alzheimer's disease (AD) neuropathology begins accumulating decades prior to symptoms so investigation of associations of adiposity with cognition in middle-aged adults may illuminate pathways underlying the earliest stages of cognitive decline. We examined the relationship of body mass index (BMI) with cognitive functioning in middle-aged adults at high AD risk due to a parental family history. We also investigated whether this association differs by maternal (FHm) versus paternal (FHp) family history. Participants are offspring of AD patients from the Israel Registry of Alzheimer's Prevention (IRAP Study; N=271). We examined the association of BMI at the time of cognitive assessment, and of long-term trajectories of BMI, with global cognition and specific cognitive domains. Linear regressions assessed the associations of BMI and cognition adjusting for sociodemographic and cardiovascular risk factors. An interaction term assessed whether associations of BMI with cognition differed by FHm/FHp. ANCOVAs examined the association of trajectories of BMI ("normal" BMI, N=154; "overweight/obese" N= 86), with cognition. For the whole sample, higher BMI was associated with worse language functioning (p=.045). Interactions of BMI with parental history of AD were significant for episodic memory (p=.023), language (p=.027), working memory (p=.006), and global cognition (p=.008), such that the associations of BMI with cognition were consistently stronger among FHm than for FHp. For the BMI trajectories, no significant differences in cognition were identified between normal and overweight/obese trajectories for the entire sample, but the interactions of BMI trajectories with parental history of AD were significant for episodic memory (p=.017), language (p=.013), working memory (p=.001), and global cognition (p=.005), with stronger associations for FHm than for FHp. Higher BMI and ∼20 years of trajectories of overweight/obesity were associated with poorer cognitive function in cognitively normal middle-aged adults with a maternal history of AD, but not in those with a paternal history of AD. Exposure to greater adiposity over time may have a detrimental impact on the brain already in midlife. Investigation of genetic and environmental contribution of maternal history of AD to these associations is merited.

Elucidating the association between depression, anxiety, and cognition in middle-aged adults: Application of dimensional and categorical approaches

BackgroundIn older adults, depressive and anxiety symptoms are associated with dementia risk, and represent a manifestation of the dementia prodrome. Understanding how these symptoms are related to cognition in midlife may inform risk models of dementia. MethodsThis study examined the relationship between depressive and anxiety symptoms, and cognition, in a sample (n= 2,657) of participants enrolled in the Healthy Brain Project. Depressive and Anxiety symptoms were assessed using the Depression Anxiety and Stress Scale, Hospital Anxiety and Depression Scale, and centre for Epidemiological Studies Depression Scale. Objective cognition was assessed using the Cogstate Brief Battery and subjective cognition assessed using the Alzheimer's disease Cooperative Study Cognitive Function Instrument. ResultsSomatic- and panic-related anxiety symptoms were associated significantly with poorer attention; while tension- and panic-related anxiety were associated significantly with poorer memory. Having clinically meaningful anxiety or depressive symptoms was associated with increased subjective cognitive concerns (d=-0.37). This was further increased for those with clinically meaningful anxiety and depressive symptoms (d = -1.07). LimitationsThis study reports cross-sectional data, and uses a sample enriched with individuals with a family history of dementia who are therefore at a higher risk of developing dementia compared to the general population. Additionally, biological markers such as cortisol, Aβ, and tau were unavailable. ConclusionThe results support the hypothesis that depressive and anxiety symptoms may increase risk of cognitive decline. Further, they suggest that using depression and anxiety as clinical markers may be helpful in identifying the earliest signs of cognitive decline.

Cognition in middle aged adults: A comparison between hypertensives and normotensives

ObjectiveThe American Heart association in December 2016 published a position paper concluding that there was insufficient data to make evidence-based recommendations on the relationship between hypertension and cognition of a person. The aim of the study was to study the effect of increased blood pressure on cognitive function. MethodsA cross sectional study of hypertensives (cases) and normotensive (controls) was done between January 2018 and December 2019. Subjects were recruited by convenience sampling. Subjects who were known cases of hypertension and had been on antihypertensive drug therapy for at least more than six months were considered as cases. Controls were those subjects who were having normal blood pressure and not suffering from any disease known to affect cognition. Out of 413 subjects, data from 388 subjects was used in the study (200 cases, 188 controls). The subjects were allowed to rest for 5min before measuring their blood pressure. Blood pressure was measured with a mercury sphygmomanometer in the right arm with the subject in seated position. Neuropsychological battery consisted of tests for domains of memory (auditory, visual, spatial), learning ability, attention, visuo-spatial construction, working memory. ResultsOn the neuropsychological tests, patients with hypertension had lower scores in the different domains. Age, hypertension duration, and educational level were the best predictors of cognitive impairment in patients with hypertension. ConclusionMiddle aged adults with hypertension have reduced cognitive functions as compared to normotensives.

The cross-sectional association of renal dysfunction with tests of cognition in middle-aged adults with early type 2 diabetes: The GRADE Study.

The association of renal dysfunction with tests of cognition in type 2 diabetes has been examined in individuals with moderate and advanced renal disease. Here we examine the association of renal dysfunction with tests of cognition in a cohort of middle-aged adults with short duration diabetes (mean 4.0 ± 2.8 years). Baseline data were examined from the Glycemia Reduction Approaches in Diabetes (GRADE) study (n = 4998). Renal dysfunction was defined by the presence of albumin in the urine or by estimated glomerular filtration rate (eGFR). Cognition was assessed with the Spanish English Verbal Learning Test, Letter and Animal fluency tests, and the Digit Symbol Substitution Test. Participants with albuminuria or eGFR <60 ml/min/1.73 m2 had significantly lower test scores of information processing speed and perception, executive function and ability to categorize information, and of verbal learning and memory compared to participants without renal disease. Adjustment for hypertension, dyslipidemia, and waist circumference attenuated many of these findings but markers of impaired learning and executive function continued to remain lower in association with higher urine albumin levels. In type 2 diabetes of short duration, there are already subtle deficiencies in markers of cognition in association with renal disease in middle aged adults.

Visual Memory Deficits in Middle-Aged APOEɛ4 Homozygotes Detected Using Unsupervised Cognitive Assessments.

The apolipoprotein E (APOE) ɛ4 allele is associated with dose-response effects on cognitive dysfunction and dementia risk in older adults. However, its effects on cognition in middle-aged adults remains unclear. We examined effects of ɛ4 heterozygosity and homozygosity on objective and subjective cognition in middle-aged adults enrolled in the Healthy Brain Project (HBP) and in older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. HBP participants (1,000 non-carriers; 450 ɛ4 heterozygotes; 50 ɛ4 homozygotes) completed unsupervised assessments of the Cogstate Brief Battery (CBB), ratings of subjective cognitive function and provided a saliva sample. AIBL cognitively normal participants (650 non-carriers; 204 ɛ4 heterozygotes; 31 ɛ4 homozygotes) completed in-person assessments of the CBB, ratings of subjective cognitive function and provided a blood sample. Greater memory impairment was observed in middle-aged ɛ4 homozygotes compared with ɛ4 heterozygotes and non-carriers. When data from middle-aged (HBP) and older (AIBL) adults were pooled, the effect of ɛ4 homozygosity and memory impairment increased with age. In both middle-aged and older adults, ɛ4 heterozygotes did not differ from non-carriers on any measure of objective or subjective cognition. Memory impairment in ɛ4 homozygotes is evident in adults aged 50-60 years, and this can be detected through unsupervised cognitive assessments. The effect of ɛ4 homozygosity increases with older age. APOEɛ4 homozygosity has a negative impact on memory as early as midlife, but due to the subtle magnitude of effect, our findings support the necessity of online platforms in large cohorts to assess these complex relationships.

Long-term trajectories and current BMI are associated with poorer cognitive functioning in middle-aged adults at high Alzheimer's disease risk.

IntroductionWe examined relationships of body mass index (BMI) with cognition in middle‐aged adults at Alzheimer's disease (AD) risk due to parental family history.MethodsParticipants are offspring of AD patients from the Israel Registry of Alzheimer's Prevention (N = 271). Linear regressions assessed associations of BMI and cognition, and whether associations differed by maternal/paternal history. Analyses of covariance examined associations of long‐term trajectories of BMI with cognition.ResultsHigher BMI was associated with worse language (P = .045). Interactions of BMI with parental history were significant for episodic memory (P = .023), language (p = .027), working memory (P = .006), global cognition (P = .008); associations were stronger among participants with maternal history. Interactions of BMI trajectories with parental history were significant for episodic memory (P = .017), language (P = .013), working memory (P = .001), global cognition (P = .005), with stronger associations for maternal history.DiscussionHigher BMI and overweight/obese trajectories were associated with poorer cognition in adults with maternal history of AD, but not those with paternal history.

Metabolic Syndrome and Cognitive Function in Midlife.

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors associated with cognitive decline. We investigated the relationship between MetS and cognition in middle-aged adults. We hypothesized that higher numbers of MetS components will relate to poorer performance on executive function (EF) tasks as frontal lobe regions critical to EF are particularly vulnerable to cardiovascular disease. 197 adults (ages 40-60) participated. MetS was evaluated using established criteria. Composite scores for cognitive domains were computed as follows: Global cognitive function (subtests from the Wechsler Abbreviated Scale of Intelligence, 2nd Edition), EF (Stroop Color Word, Digit Span Backward, and Trails A and B), and memory (California Verbal Learning Test, 2 Edition). Higher number of MetS components was related to weaker EF-F(4, 191)=3.94, p=.004, MetS components ß=-.14, p=.044. A similar relationship was detected for tests of memory-F(4, 192)=7.86, p<.001, MetS components ß=-.15, p=.032. Diagnosis of MetS was not significantly associated with EF domain score (ß=-.05, p=.506) but was significantly associated with memory scores-F(4, 189)=8.81, p<.001, MetS diagnosis ß=-.19, p=.006. Our findings support prior research linking MetS components at midlife to executive dysfunction and demonstrate that MetS, and its components are also associated with poorer memory function. This suggests that cognitive vulnerability can be detected at midlife. Interventions for MetS at midlife could alter cognitive outcomes.

Interaction between Alcohol Consumption and Apolipoprotein E (ApoE) Genotype with Cognition in Middle-Aged Men.

Heavy alcohol consumption is associated with poorer cognitive function in older adults. Although understudied in middle-aged adults, the relationship between alcohol and cognition may also be influenced by genetics such as the apolipoprotein (ApoE) ε4 allele, a risk factor for Alzheimer's disease. We examined the relationship between alcohol consumption, ApoE genotype, and cognition in middle-aged adults and hypothesized that light and/or moderate drinkers (≤2 drinks per day) would show better cognitive performance than heavy drinkers or non-drinkers. Additionally, we hypothesized that the association between alcohol use and cognitive function would differ by ApoE genotype (ε4+ vs. ε4-). Participants were 1266 men from the Vietnam Era Twin Study of Aging (VETSA; M age = 56; range 51-60) who completed a neuropsychological battery assessing seven cognitive abilities: general cognitive ability (GCA), episodic memory, processing speed, executive function, abstract reasoning, verbal fluency, and visuospatial ability. Alcohol consumption was categorized into five groups: never, former, light, moderate, and heavy. In fully adjusted models, there was no significant main effect of alcohol consumption on cognitive functions. However, there was a significant interaction between alcohol consumption and ApoE ε4 status for GCA and episodic memory, such that the relationship of alcohol consumption and cognition was stronger in ε4 carriers. The ε4+ heavy drinking subgroup had the poorest GCA and episodic memory. Presence of the ε4 allele may increase vulnerability to the deleterious effects of heavy alcohol consumption. Beneficial effects of light or moderate alcohol consumption were not observed.

Associations of Hearing Sensitivity, Higher-Order Auditory Processing, and Cognition Over Time in Middle-Aged Adults.

Age-related hearing loss (impairment in hearing sensitivity and/or higher-order auditory processing) and cognitive decline are common co-occurring impairments in elderly adults. Their relation in the process of aging remains insufficiently understood. We aim to assess the temporal relations of decline in hearing sensitivity, higher-order auditory processing, and cognition in middle-aged adults. This study included 1,274 Beaver Dam Offspring Study participants who participated in three examinations (baseline, 5-year, and 10-year follow-up). We assessed hearing sensitivity through pure-tone audiometry (PTA, averaged thresholds of 0.5, 1, 2, 4 kHz of the better ear), higher-order auditory processing as word recognition in competing message (WRCM) using the Northwestern University 6 word list in the better ear, and cognition through trail-making test performance (TMT). Linear mixed-effects models and linear regression models were used to determine associations over time and to what extent these measures influence each other over time. The longitudinal decline between all functions was associated with the strongest relationships between PTA and WRCM. The effect of baseline PTA on WRCM 10 years later (standardized ß = -.30) was almost twice as big as the effect of baseline WRCM on PTA 10 years later (standardized ß = -.18). The effect of baseline WRCM on TMT 10 years later and vice versa were small (standardized ß = -.05). No directional relationship between PTA and TMT was identified (standardized ß ≤ .02). While hearing sensitivity might affect higher-order auditory processing, associations between hearing and cognition appear bidirectional and weak in midlife. We need to be cautious before inferring causal effects of hearing on cognition.

Genetic modifiers of insulin resistance and its impact on brain and cognition in middle-aged adults at risk for Alzheimer’s disease

Genetic modifiers of insulin resistance and its impact on brain and cognition in middle-aged adults at risk for Alzheimer’s disease

Effects of Simvastatin on Cerebrospinal Fluid Biomarkers and Cognition in Middle-Aged Adults at Risk for Alzheimer's Disease

Statins reduce amyloid-beta (Abeta) levels in the brain and cerebrospinal fluid (CSF) in animals and may thereby favorably alter the pathobiology of AD. It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD. In a 4-month randomized, double-blind, controlled study, we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Abeta42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD. Compared to placebo, individuals randomized to simvastatin for 4 months had similar changes in CSF Abeta42 (p=0.344) and total tau levels (p=0.226), yet greater improvements in some measures of verbal fluency (p=0.024) and working memory (p=0.015). APOE4 genotype, gender, and vascular risk factors were associated with CSF biomarker levels, but did not modify treatment effects. In asymptomatic middle-aged adults at increased risk for AD, simvastatin use improved selected measures of cognitive function without significantly changing CSF Abeta42 or total tau levels. Further studies are needed to clarify the impact of higher dose and/or longer duration statin therapy on not only Abeta metabolism, but also other preclinical processes related to the development of AD.

Effects of alcohol and cigarette use on cognition in middle-aged adults.

In this retrospective cohort study we examined the independent and interactive effects of drinking and smoking on cognition in a sample of 3361 males, ages 31 to 49, with varying lifetime histories of alcohol and cigarette use. Dependent variables were neuropsychological measures of global and specific cognitive abilities. Comparison of the ability scores of seven groups, defined by their drinking and smoking histories, explained only 5.4% of the multivariate variance in cognitive ability and less than 2% in any individual cognitive measure. Regression analyses for current drinkers and smokers showed only a single significant, but negligible, effect of pack-years of smoking on a measure of global cognitive ability. Differences in cognitive function in groups defined by intensity of alcohol and cigarette use revealed no significant effect for drinking and a significant, but very small, effect for smoking.