Risk Of Incident Cognitive Decline Research Articles

Association of long-term exposure to various ambient air pollutants, lifestyle, and genetic predisposition with incident cognitive impairment and dementia

BackgroundLong-term exposure to air pollution has been found to contribute to the development of cognitive decline. Our study aimed to assess the association between various air pollutants and cognitive impairment and dementia. Additionally, explore the modification effects of lifestyle and genetic predisposition.MethodsThe exposure levels to various air pollutants, including particulate matter (PM) with diameters ≤ 2.5 (PM2.5), ≤ 10 (PM10), and between 2.5 and 10 μm (PM2.5−10) and nitrogen oxides (NO and NO2) were identified. An air pollution score (APS) was calculated to evaluate the combined exposure to these five air pollutants. A genetic risk estimate and healthy lifestyle score (HLS) were also generated. The Cox regression model adjusted by potential confounders was adopted to access the association between pollution exposure and cognitive decline, and several sensitivity analyses were additionally conducted to test the robustness.ResultsThe combined exposure to air pollutants was associated with an increased risk of incident cognitive decline. Compared with the low exposure group, the hazard ratio (HR) and 95% confidence interval (CI) for all-cause dementia, Alzheimer’s dementia, vascular dementia, and mild cognitive impairment (MCI) in those exposed to the highest levels of air pollutants were respectively 1.07 (95% CI: 1.04 to 1.09), 1.08 (95% CI: 1.04 to 1.12), 1.07 (95% CI: 1.02 to 1.13), and 1.19 (95% CI: 1.12 to 1.27). However, the modification effects from genetic predisposition were not widely observed, while on the contrary for the healthy lifestyle. Our findings were proven to be reliable and robust based on the results of sensitivity analyses.ConclusionsExposure to air pollution was found to be a significant contributing factor to cognitive impairment and dementia, and this association was not easily modified by an individual’s genetic predisposition. However, adopting a healthy lifestyle may help to manage the risk of cognitive decline related to air pollution.

Characterising mild behavioural impairment in Asian mild cognitive impairment and cognitively normal individuals

AbstractBackgroundMild Behavioural Impairment (MBI) is a neurobehavioral syndrome characterized by later‐life emergent and sustained neuropsychiatric symptoms that is associated with higher risk of incident cognitive decline and dementia. While MBI is common in both subjective and mild cognitive impairment (MCI), most findings are based on Caucasians and the literature of MBI among Asians remains sparse. Here, we aim to investigate the frequency of MBI and its relationship with cognition, sleep and mood symptoms among cognitively intact (CN) and MCI Asians.Method162 subjects (80 CN and 82 MCI) with a Clinical Dementia Rating of 0 or 0.5 were recruited from an outpatient neurology clinic (National Neuroscience Institute, Singapore). All subjects were administered a comprehensive neuropsychological assessment, the Pittsburgh Sleep Quality Index (PSQI) and the MBI‐checklist (MBI‐C). The presence of MBI was determined based on published cut‐offs of 6.5 for MCI and 8.5 for CN. Regression models evaluated the relationships between MBI and cognition, sleep and mood.Result29 out of 162 subjects (17.9%) had MBI (28.0% of MCI and 7.5% of CN). Subjects with MBI had poorer global cognition (p=.029) and attention/working memory (p=.049). Specifically, we found that interest and impulse control subdomains of the MBI‐C were associated with poorer performance on the global cognition tests. In addition, those with MBI had sleep‐related daytime dysfunction (p=.008), poorer GDS and DASS scores (p<.01 or p<.001).ConclusionMBI in common among our Asian cohort and is associated with poorer cognitive performance, sleep and mood symptoms. Our findings further support the utility of MBI in clinical practice to identify individuals with early presentation of neurodegenerative diseases so as to provide a window of opportunity for early interventions to improve clinical outcomes.

ApoE ε4 status in pre‐dementia risk states, mild behavioural impairment and subjective cognitive decline, and the risk of incident cognitive decline

AbstractBackgroundDementia has an increasing global burden with over 40 million affected individuals. With sub‐optimal advances in drug development, there is an increasing shift to determine risk of dementia in the non‐demented population. Assessment of neuropsychiatric symptoms (NPS) may offer an opportunity to capture the at‐risk group earlier. Mild Behavioural Impairment (MBI) is a validated neurobehavioural syndrome, characterized by the emergence of sustained NPS in older adults as an at‐risk state for dementia. Cognitively, subjective cognitive decline (SCD) is a dementia at‐risk group in which cognitive symptoms are reported in the absence of objective findings. The apolipoprotein epsilon 4 (ApoE ε4) gene is a well‐known risk marker for dementia. We aim to determine the frequency of ApoE homozygosity in SCD, stratified by MBI status cross‐sectionally, and calculate the hazard of incident cognitive decline in this group longitudinally.MethodData from 5005 participants in the National Alzheimer’s Coordinating Center (NACC) were used to capture older adults who were cognitively normal, but had subjective cognitive complaints (SCD). We determined MBI status (+/‐) using a previously published transformation algorithm of NPI‐Q scores. We tabulated ApoE genotype in both groups. We compared proportion of ApoE homozygousity (APOE ε4+/+)in the MBI+ versus the MBI‐ group. Additionally, a Cox proportional hazards regression will be done to capture hazard of incident mild cognitive impairment in MBI+ versus MBI‐.ResultA two‐sample test of proportions of MBI+/‐ status stratified by ApoE ε4+/+resulted in significant differences between groups with homozygosity more frequent in MBI+ versus MBI‐ (p<0.001). We will also present the results of the Cox proportional hazards regression analysis.ConclusionIn older adults with subjective cognitive decline, ApoE ε4 allele homozygosity was more frequently seen in the MBI+ group. These findings provide additional evidence for the utility in determining MBI status in SCD.

Adverse life events and late-life cognitive decline in a Chinese cohort: The Shanghai Aging Study.

This study aimed to demonstrate the association between adverse life events (ALEs) and the risk of late-life cognitive decline in older community-dwelling individuals in China. We prospectively followed up 1657 dementia-free participants with ALE data at baseline in the Shanghai Aging Study. The cohort was categorized into four subgroups (depression with ALEs, depression without ALEs, no depression with ALEs, and no depression without ALEs). Cox regressions were conducted to estimate the hazard ratio (HR) for incident dementia stratified by all participants and depressed and nondepressed participants. We identified 168 incident dementia cases over a mean period of 5.2 years. The cumulative dementia incidence in nondepressed participants with ALEs was the lowest among the four subgroups. Nondepressed participants with ALEs had a lower risk of incident dementia (HR [95% CI]: 0.50 [0.27-0.92], P = .0267) than those without ALEs, adjusted for age, sex, education, apolipoprotein E ε4 (APOE ε4), body mass index, cigarette smoking, heart disease, hypertension, diabetes, stroke, Mini-Mental State Examination (MMSE) at baseline, and anxiety. This study explored a significant inverse association between ALEs and the risk of incident cognitive decline among older adults without depression in China. Interventions for depression prevention immediately after ALEs may reduce the risk of cognitive decline later in life.

Neuropsychiatric Correlates of Small Vessel Disease Progression in Incident Cognitive Decline: Independent and Interactive Effects.

Cerebral small vessel disease (SVD) and neuropsychiatric symptoms (NPS) independently increase the risk of cognitive decline. While their co-existence has been reported in the preclinical stage of dementia, longitudinal data establishing the prognosis of their associations, especially in an Asian context remains limited. This study investigated the role of SVD and NPS progressions on cognitive outcomes over 2 years in a dementia-free elderly cohort. 170 dementia-free elderly with baseline and 2-year neuropsychological assessments and MRI scans were included in this study. White matter hyperintensities (WMH), lacunes, and microbleeds (CMBs) were graded as markers of SVD. The Neuropsychiatric Inventory (NPI) was used to measure NPS. Generalized estimating equations modelling evaluated the relationship between NPI change and SVD progression. Logistic regression evaluated the risk of incident cognitive decline with both SVD and NPS. All models were adjusted for demographics, baseline cerebrovascular diease, and medial temporal lobe atrophy. Higher NPI scores were associated with higher SVD burden at baseline. Subjects with WMH progression had greater increase in total NPI (β[SE] = 0.46[0.19], p = 0.016), driven by hyperactivity subsyndrome (β[SE] = 0.88[0.34], p = 0.007). Subjects with incident CMBs had greater increase in psychosis subsyndrome (β[SE] = 0.89[0.30], p < 0.001). Subjects with progressions in both SVD and NPS were more likely to develop cognitive decline over 2 years (OR[95% CI] = 4.17[1.06-16.40], p < 0.05). Our findings support worsening of NPS as a clinical indicator of SVD progression and are associated with cognitive decline over 2 years. Early detection of NPS and targeted interventions on SVD burden may improve NPS outcomes.

Agitation and impulsivity in mid and late life as possible risk markers for incident dementia.

To identify knowledge gaps regarding new‐onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre‐dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late‐onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre‐dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre‐dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.

Common bacterial infections and risk of incident cognitive decline or dementia: a systematic review protocol

IntroductionThe global burden of dementia is rising, emphasising the urgent need to develop effective approaches to risk reduction. Recent evidence suggests that common bacterial infections may increase the risk of...

Trajectory of blood pressure, body mass index, cholesterol and incident dementia: systematic review.

The global ageing population and the long prodromal period for the development of cognitive decline and dementia brings a need to understand the antecedents of both successful and impaired cognitive ageing. It is increasingly apparent that the trajectory of risk-factor change, as well as the level of the risk factor, may be associated with an increased or decreased risk of cognitive decline or dementia. Our aim was to summarise the published evidence and to generate hypotheses related to risk-factor trajectories and risk of incident cognitive decline or dementia. We collated data from longitudinal observational studies relating to trajectory of blood pressure, obesity and cholesterol and later cognitive decline or dementia using standard systematic review methodology. The databases MEDLINE, Embase and PsycINFO were searched from inception to 26 April 2018. Thirteen articles were retained for inclusion. Analytical methods varied. Our summary of the current evidence base suggests that first body mass index and then blood pressure rises and then falls more steeply in those who go on to develop dementia. The evidence for cholesterol was less consistent. Based on our review we present the hypothesis that weight falls around 10 years and blood pressure around 5 years before diagnosis. Confirmatory work is required. However, characterisation of risk according to combinations and patterns of risk factors may ultimately be integrated into the assessments used to identify those at risk of receiving a diagnosis of cognitive decline or dementia in late life.

Elevated Fasting Blood Glucose Level Increases the Risk of Cognitive Decline Among Older Adults with Diabetes Mellitus: The Shanghai Aging Study

Several studies have demonstrated that the elevated fasting blood glucose (FBG) may increase the risk of incident dementia in older adults with or without diabetes mellitus (DM). However, similar results are rarely reported in Chinese population. This study aimed to demonstrate the association between FBG and risk of incident cognitive decline in older Chinese adults. We prospectively followed up 1,555 dementia-free participants with baseline FBG measurement in the Shanghai Aging Study. We identified 126 incident dementia cases across a mean of 5.2 years. Cumulative dementia incidence in type II DM participants with higher FBG (>6.1 mmol/L) increased most dramatically, second with that of non-DM participants with higher FBG, than that of participants with lower FBG (≤6.1 mmol/L). DM participants had a significant higher risk of incident dementia (adjusted HR 1.51, 95% CI 1.25-1.82) by every 1 mmol/L increment of FBG. Among DM participants, baseline FBG was positively related to the rate of annual decline of MMSE (β= 0.10, p = 0.0018). Our results suggest that especially in people with type II DM, effective blood glucose control may help to prevent cognitive impairment in later life.

Subjective memory complaints and incident dementia in a high risk older adult hypertensive population.

there is a growing body of evidence demonstrating an association between subjective memory complaints (SMC) and an increased risk of incident cognitive decline or dementia. To date this has not been examined in hypertensive older adults, a prevalent and growing population group at high risk of cognitive decline. using data from participants in the Hypertension in the Very Elderly Trial cohort the association between baseline SMC and incident cognitive decline and dementia was examined using Cox proportional hazard regression. Cognitive function was assessed using the Mini-Mental State Exam and diagnoses of dementia were made using standard diagnostic criteria. SMC was assessed by the question 'do you feel that you have more problems with memory than most?' Analyses were rerun to examine the associations by level of baseline cognitive function, to evaluate the role of SMC by dementia type and by sex. baseline SMC were associated with an increased risk of developing any dementia (hazard ratio (HR)1.63 (95% confidence intervals (CI): 1.18:2.25)), Alzheimer's disease (HR1.59 (95% CI: 1.08:2.34)) and vascular dementia (HR2.05 (95% CI: 1.19:3.54)). Similar patterns were seen across all levels of baseline MMSE but were strongest in those with scores of 25-27. There were no clear differences by sex. a positive report of SMC assessed by a single question in an older adult with hypertension raises the possibility of increased risk of incident dementia. As such its use may be a useful addition to the repertoire of the general practitioner and geriatrician when assessing older adults.

Sensorial frailty: age-related hearing loss and the risk of cognitive impairment and dementia in later life.

The peripheral hearing alterations and central auditory processing disorder (CAPD) associated with age-related hearing loss (ARHL), may impact cognitive disorders in older age. In older age, ARHL is also a significant marker for frailty, another age-related multidimensional clinical condition with a nonspecific state of vulnerability, reduced multisystem physiological reserve, and decreased resistance to different stressors (i.e. sensorial impairments, psychosocial stress, diseases, injuries). The multidimensional nature of frailty required an approach based on different pathogeneses because this clinical condition may include sensorial, physical, social, nutritional, cognitive, and psychological phenotypes. In the present narrative review, the cumulative epidemiological evidence coming from several longitudinal population-based studies, suggested convincing links between peripheral ARHL and incident cognitive decline and dementia. Moreover, a few longitudinal case-control and population-based studies also suggested that age-related CAPD in ARHL, may be central in determining an increased risk of incident cognitive decline, dementia, and Alzheimer’s disease (AD). Cumulative meta-analytic evidence confirmed cross-sectional and longitudinal association of both peripheral ARHL and age-related CAPD with different domains of cognitive functions, mild cognitive impairment, and dementia, while the association with dementia subtypes such as AD and vascular dementia remained unclear. However, ARHL may represent a modifiable condition and a possible target for secondary prevention of cognitive impairment in older age, social isolation, late-life depression, and frailty. Further research is required to determine whether broader hearing rehabilitative interventions including coordinated counseling and environmental accommodations could delay or halt cognitive and global decline in the oldest old with both ARHL and dementia.

White Matter Hyperintensity Predicts the Risk of Incident Cognitive Decline in Community Dwelling Elderly.

Unlike western countries, data on white matter hyperintensity (WMH) in community dwelling elderly in Asian population is very limited. To examine the relation between baseline WMH burden and the risk of incident cognitive decline in a community-based cohort with Chinese-dwelling elderly. We prospectively evaluated the incident cognitive decline for 226 participants in the Shanghai Aging Study. Baseline WMH severity was visually rated by the age-related white matter changes (ARWMC) scale based on MRI. Cox proportional hazards regression model was used to estimate the relative risk (RR) of total ARWMC scale, global ARWMC score, presence of lacune and microbleed, for incident cognitive decline by adjusting potential confounders. Forty subjects were identified with incident cognitive decline (new onset 34 mild cognitive impairment and 6 dementia) during a median duration of 6 years follow-up. The incidence of cognitive decline was 3.0 (95% confidence interval [CI] 2.2-4.1) per 100 person-years. Increasing total ARWMC scale [RR1.21 (95% CI 1.06-1.39), p = 0.004)], confluent WMH [RR3.16 (95% CI 1.50-6.64), p = 0.002), and presence of lacunes [RR 2.73 (95% CI 1.21-6.15)] at baseline were independent predictors of incident cognitive decline. Our study demonstrated that confluent WMH may increase the risk of incident cognitive decline by 3 folds in community dwelling subjects. Small vessel disease may cause heavy burden of cognitive impairment in the elderly in China.

Regular aspirin use does not reduce risk of incident cognitive decline (P7.117)

Regular aspirin use does not reduce risk of incident cognitive decline (P7.117)