Association of geriatric conditions and cardiovascular diseases with disability in older adults with diabetes: findings from a nationally representative survey.
Li Chia-Lin,Chiu Yi-Chen,Chang Hsing-Yi,Hsu Kuang-Hung,Bai Yuh-Bin,Wang Hui-Hsuan
Geriatrics & gerontology international
AIM:To examine how diabetes in combination with cardiovascular diseases (hypertension, heart disease and stroke) and geriatric conditions (cognitive impairment and depressive symptoms) affects the odds of disability in older adults. METHODS:We analyzed data from a nationally representative sample of people aged 65 years and over (n=2727) participating in the 2005 National Health Interview Survey in Taiwan. A total of 473 participants had a history of self-reported physician diagnosed diabetes. Disability was defined as reporting limitations in one or more tasks of activities of daily living (ADL), instrumental activities of daily living (IADL) or general physical activities (GPA). The Mini-Mental State Examination was used to assess cognitive function. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms. RESULTS:After adjustment for other factors, cardiovascular diseases and geriatric conditions independently contributed to the excess odds of disability among participants with diabetes. Participants who had diabetes combined with cardiovascular diseases and geriatric conditions had odds ratios for ADL, IADL and GPA disability of 18.02 (95% CI 5.13-63.34), 7.95 (95% CI 4.07-15.50) and 5.89 (95% CI 3.19-10.90), respectively. CONCLUSION:Our results highlight the high prevalence of co-occurrence of cardiovascular diseases with geriatric conditions in people with diabetes. Furthermore, the combined presence of these diseases and conditions is strongly associated with an excess odds of disability. These findings highlight the critical importance of preventing cardiovascular disease morbidity, and improving depressed mood and cognitive function in order to reduce disability risk in older adults with diabetes.
Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort.
Luchsinger J A,Tang M X,Stern Y,Shea S,Mayeux R
American journal of epidemiology
Research on the relation between diabetes mellitus and dementia has produced conflicting results, and the relation has not been investigated among Blacks and Hispanics. In this study, Cox proportional hazards models were used to analyze longitudinal data from 1,262 elderly subjects without dementia at baseline (1991-1996) who were followed for an average of 4.3 years between 1992 and 1997. Outcomes were incident Alzheimer's disease and dementia associated with stroke. The prevalence of diabetes was 20% at baseline. The adjusted relative risk of Alzheimer's disease among persons with diabetes as compared with those without diabetes was 1.3 (95% confidence interval (CI): 0.8, 1.9). The adjusted relative risk for the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) in subjects with diabetes was 1.6 (95% CI: 1.2, 2.1). The adjusted relative risk of stroke-associated dementia in persons with diabetes was 3.4 (95% CI: 1.7, 6.9). Among Blacks and Hispanics, approximately one third of the risk of stroke-associated dementia was attributable to diabetes (33% (95% CI: 31, 36) and 36% (95% CI: 33, 37), respectively), as compared with 17% (95% CI: 13, 22) among Whites. The finding of an association between diabetes and the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) is consistent with prior reports of a modest relation between diabetes and Alzheimer's disease.
Cognitive Decline in Adults Aged 65 and Older in Cumbayá, Quito, Ecuador: Prevalence and Risk Factors.
Espinosa Del Pozo Patricio H,Espinosa Patricio S,Donadi Eduardo A,Martinez Edson Z,Salazar-Uribe Juan C,Guerrero Marco A,Moriguti Julio C,Colcha Mishell C,Garcia Susana E,Naranjo Raquel,Altamirano Wilson E,Koek Adriana Y
Objective To assess the prevalence of and risk factors for cognitive decline and dementia in individuals greater than 65 years of age in Cumbayá, Quito, Ecuador. Methods This is a cross-sectional observational study that was carried out in adults over age 65. The Mini Mental State Examination (MMSE), Ascertain Dementia Eight-Item Informant Questionnaire (AD8), and Mini Nutritional Assessment (MNA) were used to assess the cognitive status and nutritional habits of this population. Results A total of 144 patients (mean age 75.3 years, 77.1% female) participated in this study. Forty percent of patients had AD8 and MMSE scores consistent with cognitive impairment and possible dementia. Age (p < 0.01), lower educational level (p < 0.01), history of stroke (p < 0.01), history of intracerebral hemorrhage (p < 0.01), diabetes mellitus (p < 0.01), and malnutrition (p < 0.01) were statistically significant risk factors for cognitive impairment. Exercise was found to be protective against cognitive decline in our study group (p < 0.03). Gender, ethnicity, location, head trauma, Parkinson disease, hypercholesterolemia, myocardial infarction, thyroid disease, depression, anxiety, and family history of dementia were not found to be associated with cognitive decline in this population. Conclusions The prevalence of cognitive impairment and possible dementia is 18-21% at age 65 and 54-60% at age 85 in Cumbayá, Quito, Ecuador. The major risk factors for cognitive impairment in this population are age, low educational level, malnutrition, prior stroke, prior intracerebral hemorrhage, and diabetes. Protective factors for cognitive decline include exercise and possibly modest consumption of alcohol.
Stroke Risk and Vascular Dementia in South Asians.
Singh Vineeta,Dhamoon Mandip S,Alladi Suvarna
Current atherosclerosis reports
PURPOSE OF REVIEW:South Asians (SA) are at a higher risk for stroke and vascular dementia due to the disproportionate burden of diabetes, hypertension, and dyslipidemia. This review summarizes the rationale for screening, early detection, and aggressive control of metabolic factors, and critically examines the published literature on primary and secondary stroke prevention. RECENT FINDINGS:South Asians have a higher prevalence of diabetes than non-SA. SA with diabetes are at a higher risk of recurrent ischemic stroke and have a higher incidence of stroke-related dementia compared to non-South Asians. South Asians are one of the fastest-growing ethnic groups worldwide with an unusually increased risk of heart disease and stroke. An accurate assessment of those at risk of stroke and cognitive impairment is urgently needed to plan preventive strategies.
Sex differences in risk factors for vascular contributions to cognitive impairment & dementia.
Gannon O J,Robison L S,Custozzo A J,Zuloaga K L
Vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia. While males overall appear to be at a slightly higher risk for VCID throughout most of the lifespan (up to age 85), some risk factors for VCID more adversely affect women. These include female-specific risk factors associated with pregnancy related disorders (e.g. preeclampsia), menopause, and poorly timed hormone replacement. Further, presence of certain co-morbid risk factors, such as diabetes, obesity and hypertension, also may more adversely affect women than men. In contrast, some risk factors more greatly affect men, such as hyperlipidemia, myocardial infarction, and heart disease. Further, stroke, one of the leading risk factors for VCID, has a higher incidence in men than in women throughout much of the lifespan, though this trend is reversed at advanced ages. This review will highlight the need to take biological sex and common co-morbidities for VCID into account in both preclinical and clinical research. Given that there are currently no treatments available for VCID, it is critical that we understand how to mitigate risk factors for this devastating disease in both sexes.
Neuropsychological profiles of vascular disease and risk of dementia: implications for defining vascular cognitive impairment no dementia (VCI-ND).
Stephan Blossom Christa Maree,Minett Thais,Muniz-Terrera Graciela,Harrison Stephanie L,Matthews Fiona E,Brayne Carol
Age and ageing
Background:vascular cognitive impairment no dementia (VCI-ND) defines a preclinical phase of cognitive decline associated with vascular disorders. The neuropsychological profile of VCI-ND may vary according to different vascular conditions. Objective:to determine the neuropsychological profile of individuals with no dementia and vascular disorders, including hypertension, peripheral vascular disease (PVD), coronary heart disease (CHD), diabetes and stroke. Risk of 2-year incident dementia in individuals with disease and cognitive impairment was also tested. Methods:participants were from the Cognitive Function and Ageing Study. At baseline, 13,004 individuals aged ≥65 years were enrolled into the study. Individuals were grouped by baseline disorder status (present, absent) for each condition. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). Dementia was assessed at 2 years. Results:in the cross-sectional analysis, hypertension, PVD and CHD were not associated with cognitive impairment. Stroke was associated with impaired global (MMSE) and CAMCOG sub-scale (including memory and non-memory) scores. Diabetes was associated with impairments in global cognitive function (MMSE) and abstract thinking. In the longitudinal analysis, cognitive impairments were associated with incident dementia in all groups. Conclusion:the neuropsychological profile in individuals with vascular disorders depends on the specific condition investigated. In all conditions cognitive impairment is a risk factor for dementia. A better understanding of which cognitive domains are affected in different disease groups could help improve operationalisation of the neuropsychological criteria for VCI-ND and could also aid with the development of dementia risk prediction models in persons with vascular disease.
Post-stroke cognitive impairment: high prevalence and determining factors in a cohort of mild stroke.
Jacquin Agnès,Binquet Christine,Rouaud Olivier,Graule-Petot Anny,Daubail Benoit,Osseby Guy-Victor,Bonithon-Kopp Claire,Giroud Maurice,Béjot Yannick
Journal of Alzheimer's disease : JAD
BACKGROUND:Because of the aging population and a rise in the number of stroke survivors, the prevalence of post-stroke cognitive impairment (PSCI) is increasing. OBJECTIVE:To identify the factors associated with 3-month PSCI. METHODS:All consecutive stroke patients without pre-stroke dementia, mild cognitive disorders, or severe aphasia hospitalized in the Neurology Department of Dijon, University Hospital, France (November 2010 - February 2012) were included in this prospective cohort study. Demographics, vascular risk factors, and stroke data were collected. A first cognitive evaluation was performed during the hospitalization using the Mini-Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MOCA). Patients assessable at 3 months were categorized as cognitively impaired if the MMSE score was ≤26/30 and MOCA <26/30 or if the neuropsychological battery confirmed PSCI when the MMSE and MOCA were discordant. Multivariable logistic models were used to determine factors associated with 3-month PSCI. RESULTS:Among the 280 patients included, 220 were assessable at 3 months. The overall frequency of 3-month PSCI was 47.3%, whereas that of dementia was 7.7%. In multivariable analyses, 3-month PSCI was associated with age, low education level, a history of diabetes mellitus, acute confusion, silent infarcts, and functional handicap at discharge. MMSE and MOCA scores during hospitalization were associated with 3-month PSCI (OR = 0.63; 95% CI: 0.54-0.74; p < 0.0001 and OR = 0.67; 95% CI: 0.59-0.76; p < 0.0001, respectively). CONCLUSION:Our study underlines the high frequency of PSCI in a cohort of mild stroke. The early cognitive diagnosis of stroke patients could be useful by helping physicians to identify those at a high risk of developing PSCI.
One-year prospective study on the presence of chronic diseases and subsequent cognitive decline in older adults.
Bakouni Hamzah,Gontijo Guerra Samantha,Chudzinski Veronica,Berbiche Djamal,Vasiliadis Helen-Maria
Journal of public health (Oxford, England)
Background:The literature is inconsistent regarding the effect of the presence of chronic physical and mental diseases on cognitive decline in older adults. The objectives of this study were to explore the effect of chronic diseases on subsequent cognitive decline assessed via the Mini Mental State Examination (MMSE) in community living older adults. Methods:We used data from individuals (n = 2010) participating in the ESA (Étude sur la Santé des Aînés) study. Cognitive status was measured with the MMSE at baseline and after 1 year. Chronic diseases were identified via administrative databases in accordance with International Classification of Diseases 9/10. Multivariate linear regression was used to assess the change in MMSE as a function of chronic physical and mental disorders, while adjusting for socio-demographic and clinical factors. Results:Significant decreases in MMSE scores were found in patients who had a stroke (β value: -2.83) or diabetes (β value: -1.06) and in older adults aged older than 75 years (β value: -0.91). Conclusions:When adjusting for other chronic diseases, stroke, diabetes and advanced age were associated with subsequent cognitive decline in older adults during a one-year follow-up. Longer follow-up is recommended to assess long-term effect.
Age and recurrent stroke are related to the severity of white matter hyperintensities in lacunar infarction patients with diabetes.
Yu Ling,Yang Lei,Zhang Xiaoyu,Yuan Junliang,Li Yue,Yang Shuna,Gu Hua,Hu Wenli,Gao Shan
Clinical interventions in aging
Background and purpose:White matter hyperintensities (WMH) is identified as a marker of cerebral small vessel diseases and is a major contributor to cognitive impairment, depression, gait disturbance, and urinary incontinence. However, the risk factors for WMH in patients with type 2 diabetes mellitus (T2DM) has not been well explored. Thus, in this study, we aimed to investigate the relationship between the severity of WMH and vascular risk factors in lacunar infarction patients with T2DM. Methods:Consecutive lacunar infarction patients with T2DM were recruited in this cross-sectional study. Paraventricular WMH (P-WMH) and deep WMH (D-WMH) were separately scored by the Fazekas scale, and classified into two categories by the severity. Vascular risk factors and clinical features were compared between the mild and severe WMH. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors. Results:A total of 327 participants aged 34-91 years were enrolled in this study. Compared with the patients with mild P-WMH, the patients with severe P-WMH had higher age (=0.031), higher proportion of hypertension (=0.042) and stroke (<0.001). Levels of TG, LDL, and HbA1c were significantly higher in patients with mild P-WMH. Compared with the patients with mild D-WMH the patients with severe D-WMH had higher age and hyperhomocysteinemia (HCY) level (<0.001), higher proportion of hyperlipidemia (=0.008), and stroke (<0.001). Multivariable logistic regression analyses showed that higher age and recurrent stroke were independently related to severe P-WMH and D-WMH in lacunar infarction patients with T2DM. Conclusions:Age and recurrent stroke are related to the severity of P-WMH and D-WMH in lacunar infarction patients with T2DM.
Risk factors for development of dementia in a unique six-year cohort study. I. An exploratory, pilot study of involvement of the E4 allele of apolipoprotein E, mutations of the hemochromatosis-HFE gene, type 2 diabetes, and stroke.
Percy Maire,Somerville Martin J,Hicks Mark,Garcia Angeles,Colelli Teresa,Wright Emily,Kitaygorodsky Julia,Jiang Amy,Ho Valerie,Parpia Alyssa,Wong Michael K
Journal of Alzheimer's disease : JAD
Risk factors for dementia development are not well-defined. We evaluated several factors alone and in combination in a unique cohort of Caucasian volunteers over an approximately 6-year observation window using a nested case/control design. Factors included: apolipoprotein E (ApoE) gene variants (the E4 allele is the strongest confirmed genetic predisposing factor for Alzheimer's disease), the hemochromatosis-HFE gene mutations (H63D and C282Y), diabetes, and stroke. At study entry, subjects were ≥65 years of age (M ± SD = 73.0 ± 4.9), had an MMSE score ≥24, and no evidence of cerebrovascular disease or current depression. Genotyping was completed on 163 available DNA samples from three different groups at the study end: those who still had normal cognitive function; those who had developed dementia; and those with Mild Cognitive Impairment (MCI). Analyses were interpreted at the 95% confidence level without Bonferroni corrections. In the subgroup with dementia, all cases of diabetes were type 2 and present at study entry, whereas all strokes occurred during the study. The results highlight apparently synergistic interactions between genetic and medical risk factors for dementia development, gender differences in risk factors, and involvement of HFE mutations. Having E4 (i.e., either of E3/4 or E4/4), C282Y, H63D, diabetes, or stroke alone did not attain significance. Significant predisposing factors with post-hoc power ≥80% were: E4 homozygosity (E4/4)males+females, odds ratio (OR) = 56.0); E4+diabetes (males+females, OR = 13.7; E4+H63D+diabetes (females, OR = 52.0); E4+stroke (males, OR = 46.5). The importance of preventing diabetes and stroke to ward off dementia and the possible role of iron dysmetabolism in dementia are discussed.
Stroke Symptoms With Absence of Recognized Stroke Are Associated With Cognitive Impairment and Depressive Symptoms in Older Adults With Diabetes.
Passler Jesse S,Clay Olivio J,Wadley Virginia G,Ovalle Fernando,Crowe Michael
Journal of geriatric psychiatry and neurology
Self-reported stroke symptoms may represent unrecognized cerebrovascular events leading to poorer cognitive and mental health. We examined relationships between stroke symptoms, cognitive impairment, and depressive symptoms in a high-risk sample: 247 adults aged ≥65 with diabetes. Stroke symptoms were assessed using the Questionnaire for Verifying Stroke-free Status, cognitive impairment was measured with the modified Telephone Interview for Cognitive Status, and depressive symptoms were measured using the 15-item Geriatric Depression Scale. In 206 participants without history of stroke/transient ischemic attack, 27.7% reported stroke symptoms, with sudden loss of comprehension most frequently reported (11.7%). Having >1 versus 0 stroke symptoms was associated with greater odds of cognitive impairment (odds ratio = 3.04, 95% confidence interval 1.15-8.05) and more depressive symptoms (b= 2.60,P< .001) while controlling for age, race, gender, education, diabetes duration, diabetes severity, and cardiovascular comorbidities. Better recognition and treatment of cerebrovascular problems in older adults with diabetes may lead to improved cognition and mental health.
Clinico-radiological predictors of vascular cognitive impairment (VCI) in patients with stroke: a prospective observational study.
Chaudhari Tejendra Sukdeo,Verma Rajesh,Garg Ravindra Kumar,Singh Manish Kumar,Malhotra Hardeep Singh,Sharma Praveen Kumar
Journal of the neurological sciences
BACKGROUND AND PURPOSE:Cognitive dysfunction occurs commonly following stroke and varies in severity. This study was aimed to determine the clinical, neuro-imaging, laboratory predictors of post stroke cognitive impairment and factors related to poor functional outcome in patients with post-stroke vascular cognitive impairment (VCI). MATERIAL AND METHODS:We prospectively evaluated 102 of 240 consecutive stroke patients for 6 months after incident stroke for development of VCI. Patients with VCI comprised of those with VCI-no dementia (VCIND) and vascular dementia (VaD). Functional outcome was assessed by modified Barthel index (MBI). RESULTS:Frequency of post-stroke VCI was 45.1% (46/102): 26.5% (27/102) having VCI-ND and 18.6% (19/102) having VaD. Patients with VCI were more likely to have lower educational and socioeconomic status, diabetes, hypertension, prior stroke, multiple risk factors, urinary incontinence, gait abnormality, peripheral signs of atherosclerosis, higher blood sugar level on admission and LDL levels, strategic site lesion, higher ARWMC (age related white matter changes) score, worse stroke severity (NIHSS) and functional outcome scores. On logistic regression analysis, lower educational status, strategic site lesion, higher ARWMC score and baseline stroke severity score were found to independently predict the risk of developing VCI. Worse stroke severity (NIHSS) scores and functional status scores at baseline predicted poor outcome in patients with VCI. CONCLUSION:Post-stroke cognitive impairment is frequent and is associated with poor functional outcome. Predictors like lower educational status, strategic site lesion, greater severity of age related white matter changes and baseline stroke severity independently contributed to the risk of developing VCI in stroke patients.
Mild cognitive impairment in a Spanish representative sample: prevalence and associated factors.
Lara Elvira,Koyanagi Ai,Olaya Beatriz,Lobo Antonio,Miret Marta,Tyrovolas Stefanos,Ayuso-Mateos Jose Luis,Haro Josep Maria
International journal of geriatric psychiatry
OBJECTIVE:Given the limitations of treatments for dementia, the characterisation of the early stages of dementia is crucial for the development of preventive programmes and interventions. We aimed to estimate the prevalence of mild cognitive impairment (MCI) and examine its medical and lifestyle correlates in a nationally representative sample of the Spanish population. METHODS:A total of 3625 participants (≥50 years of age) were interviewed in a cross-sectional study. MCI was defined as the presence of cognitive concerns, the objective evidence of impairment in one or more cognitive domains, the preservation of independence in functional abilities and no dementia. Participants were also asked to provide sociodemographic, health status and lifestyle information. Logistic regression analyses were performed using the overall sample and by age groups. RESULTS:The overall prevalence of MCI was 9.6%, with higher rates in older people and women. In the overall model, after adjustment for potential confounders, depression [odds ratio (OR) = 1.79; 95% confidence interval (CI) = 1.21, 2.66], diabetes (OR = 1.43; 95% CI = 1.05, 1.95), sleep disturbances (OR = 1.66; 95% CI = 1.09, 2.55) and low level of physical activity (OR = 1.71; 95% CI = 1.26, 2.31) were associated with significantly higher odds for MCI. When stratified by age groups, depression (OR = 2.41; 95% CI = 1.35, 4.31), stroke (OR = 3.77; 95% CI = 1.44, 9.83) and obesity (OR = 2.06; 95% CI = 1.20, 3.53) were significantly associated with MCI in middle-aged participants (50-64 years), whereas low level of physical activity (OR = 1.85; 95% CI = 1.32, 2.59) and sleep disturbances (OR = 1.79; 95% CI = 1.05, 3.05) were associated with MCI in individuals aged 65+ years. CONCLUSIONS:Significant associations between MCI and psychological, cardiovascular and lifestyle factors were found. Targeting modifiable risk factors might reduce the risk for MCI and subsequent dementia.
The use of MMSE and MoCA in patients with acute ischemic stroke in clinical.
Shen Yi-Jun,Wang Wen-An,Huang Fu-De,Chen Jie,Liu Hai-Yan,Xia Yi-Ling,Han Meng,Zhang Le
The International journal of neuroscience
BACKGROUND:The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are brief cognitive screening tools that have been developed for the screening of patients with Mild Cognitive Impairment. METHODS:A total of 105 patients were included in this study, aged 53-89 years, with acute ischemic stroke admitted to hospital and fell into two groups: stroke patients with cognitive impairment (SCI) and controls with no cognitive impairment (n-SCI). The patient's characteristics are collected and regression analyses were performed to predict cognitive impairments. We use MMSE and MoCA assessment as prognostic indices for cognitive impairments of patient's with stroke. OBJECTIVES:Our aim was to examine the effectiveness of the MMSE and MoCA in screening cognitive impairments. MAIN RESULTS:There were significant difference among the two groups in the prevalence of diabetes mellitus (p < 0.05) and intracranial atherosclerosis (p < 0.05). A linear regression determined that the age, diabetes, intracranial atherosclerosis predicted the cognitive impairments. The ROC results for MoCA with an AUC of 0.882 and the corresponding results for MMSE show a similar AUC of 0.839. CONCLUSION:Neuropsychological performance of stroke patients was influenced by biological and demographic variables: age, diabetes and intracranial atherosclerosis. The MoCA and MMSE are both reliable assessments for the diagnosis of cognitive impairment after stroke.
Mild cognitive impairment and depressive symptoms in elderly patients with diabetes: prevalence, risk factors, and comorbidity.
Gorska-Ciebiada Malgorzata,Saryusz-Wolska Malgorzata,Ciebiada Maciej,Loba Jerzy
Journal of diabetes research
The aim of the study was to estimate the prevalence of mild cognitive impairment (MCI), depressive syndrome cases, and its comorbidity, and to identify predictors of these conditions. Methods. 276 diabetics elders were screened for MCI and depressive symptoms. Detailed information of history of diabetes, and data of BMI, HbA1c, and blood lipids were collected. Results. The prevalence of MCI was 31.5%, depressive syndrome was 29.7%, and MCI with coexisting depressive mood was 9.1%. The logistic regression analysis revealed that variables which increased the likelihood of having been diagnosed with MCI were: higher HbA1c level, previous CVD, hypertension, retinopathy, increased number of comorbidities, and less years of formal education. Significant predictors of having a depressive mood included female gender, single marital status, current and past smoking status, lack of physical activity, higher BMI and total cholesterol level, increased number of comorbidities, history of hypoglycemia, and insulin treatment. Factors associated with both MCI and depressive syndrome were female gender, single marital status, past smoking status, retinopathy, previous CVD or stroke, increased number of comorbidities, and insulin treatment. Conclusions. Depressive symptoms, MCI, and its comorbidity are common in elderly subjects with type 2 diabetes. Systematic screening could result in the identification of high-risk patients.
Predicting dementia risk in primary care: development and validation of the Dementia Risk Score using routinely collected data.
Walters K,Hardoon S,Petersen I,Iliffe S,Omar R Z,Nazareth I,Rait G
BACKGROUND:Existing dementia risk scores require collection of additional data from patients, limiting their use in practice. Routinely collected healthcare data have the potential to assess dementia risk without the need to collect further information. Our objective was to develop and validate a 5-year dementia risk score derived from primary healthcare data. METHODS:We used data from general practices in The Health Improvement Network (THIN) database from across the UK, randomly selecting 377 practices for a development cohort and identifying 930,395 patients aged 60-95 years without a recording of dementia, cognitive impairment or memory symptoms at baseline. We developed risk algorithm models for two age groups (60-79 and 80-95 years). An external validation was conducted by validating the model on a separate cohort of 264,224 patients from 95 randomly chosen THIN practices that did not contribute to the development cohort. Our main outcome was 5-year risk of first recorded dementia diagnosis. Potential predictors included sociodemographic, cardiovascular, lifestyle and mental health variables. RESULTS:Dementia incidence was 1.88 (95% CI, 1.83-1.93) and 16.53 (95% CI, 16.15-16.92) per 1000 PYAR for those aged 60-79 (n = 6017) and 80-95 years (n = 7104), respectively. Predictors for those aged 60-79 included age, sex, social deprivation, smoking, BMI, heavy alcohol use, anti-hypertensive drugs, diabetes, stroke/TIA, atrial fibrillation, aspirin, depression. The discrimination and calibration of the risk algorithm were good for the 60-79 years model; D statistic 2.03 (95% CI, 1.95-2.11), C index 0.84 (95% CI, 0.81-0.87), and calibration slope 0.98 (95% CI, 0.93-1.02). The algorithm had a high negative predictive value, but lower positive predictive value at most risk thresholds. Discrimination and calibration were poor for the 80-95 years model. CONCLUSIONS:Routinely collected data predicts 5-year risk of recorded diagnosis of dementia for those aged 60-79, but not those aged 80+. This algorithm can identify higher risk populations for dementia in primary care. The risk score has a high negative predictive value and may be most helpful in 'ruling out' those at very low risk from further testing or intensive preventative activities.
Cortical cerebral microinfarcts on 3T MRI: A novel marker of cerebrovascular disease.
Hilal Saima,Sikking Emiel,Shaik Muhammad Amin,Chan Qun Lin,van Veluw Susanne J,Vrooman Henri,Cheng Ching-Yu,Sabanayagam Charumathi,Cheung Carol Y,Wong Tien Yin,Venketasubramanian Narayanaswamy,Biessels Geert Jan,Chen Christopher,Ikram Mohammad Kamran
OBJECTIVE:We examined the risk factors of cortical cerebral microinfarcts (CMIs) on 3T MRI and their association with cognitive impairment. METHODS:Participants (aged 60 years and older) from the multiethnic Epidemiology of Dementia In Singapore Study underwent detailed neuropsychological testing and 3T brain MRI. Cortical CMIs were graded using a previously validated protocol. Cognitive impairment was categorized into cognitive impairment, no dementia (CIND)-mild, CIND-moderate, and dementia. Cognitive function was summarized as composite and domain-specific z scores. RESULTS:Among 861 participants, 54 (6.3%) had ≥1 cortical CMI. In multivariate-adjusted models, the risk factors of cortical CMIs were increasing age, Malay ethnicity, hypertension, diabetes, history of stroke, and markers of both large (cortical infarcts and intracranial stenosis) and small (lacunar infarcts, white matter hyperintensities, cerebral microbleeds) vessel disease. Presence of cortical CMIs was associated with CIND-moderate (odds ratio: 3.12; 95% confidence interval [CI]: 1.18-8.58), dementia (odds ratio: 16.92; 95% CI: 3.37-85.05), and poorer cognitive function (mean difference in composite z score: -0.42; 95% CI: -0.62 to -0.21). Additional adjustments for vascular risk factors and other MRI markers did not alter these associations. CONCLUSIONS:Cortical CMIs are a novel MRI marker of cerebrovascular disease and are independently associated with cognitive impairment and dementia. These findings provide new insights into the burden of cerebrovascular disease in cognitive impairment. Future research is needed to establish the additional etiologic and prognostic significance of cortical CMIs.
Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease.
Malek Naveed,Lawton Michael A,Swallow Diane M A,Grosset Katherine A,Marrinan Sarah L,Bajaj Nin,Barker Roger A,Burn David J,Hardy John,Morris Huw R,Williams Nigel M,Wood Nicholas,Ben-Shlomo Yoav,Grosset Donald G,
Movement disorders : official journal of the Movement Disorder Society
OBJECTIVE:The purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD). METHODS:Recently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without functional impairment, and dementia 21 or less with functional impairment) and Movement Disorder Society Unified PD Rating Scale part 3 (UPDRS 3) scores were analyzed in relation to a history of vascular events and risk factors. RESULTS:In 1759 PD cases, mean age 67.5 (standard deviation 9.3) years, mean disease duration 1.3 (standard deviation 0.9) years, 65.2% were men, 4.7% had a history of prior stroke or transient ischemic attack, and 12.5% had cardiac disease (angina, myocardial infarction, heart failure). In cases without a history of vascular disease, hypertension was recorded in 30.4%, high cholesterol 27.3%, obesity 20.7%, diabetes 7.2%, and cigarette smoking in 4.6%. Patients with prior stroke or transient ischemic attack were more likely to have cognitive impairment (42% vs 25%) and postural instability gait difficulty (53.5% vs 39.5%), but these findings were not significant after adjustment for age, sex, and disease duration (P = .075). The presence of more than 2 vascular risks was associated with worse UPDRS 3 motor scores (beta coefficient 4.05, 95% confidence interval 1.48, 6.61, p = .002) and with cognitive impairment (ordinal odds ratio 2.24, 95% confidence interval 1.34, 3.74, p = .002). In 842 patients (47.8%) with structural brain imaging, white matter leukoaraiosis, but not lacunar or territorial infarction, was associated with impaired cognition (p = .006) and postural instability gait difficulty (p = .010). CONCLUSION:Vascular comorbidity is significantly associated with cognitive and gait impairment in patients with early PD, which may have prognostic and treatment implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Risk of prevalent and incident dementia associated with insulin-like growth factor and insulin-like growth factor-binding protein 3.
Almeida O P,Hankey G J,Yeap B B,Paul Chubb S A,Gollege J,Flicker L
Insulin-like growth factor 1 (IGF-1) influences cell proliferation and survival. In the extracellular environment, IGF-1 circulates bound to proteins (IGF-binding proteins; IGFBP), some of which have physiological effects that seem independent of IGF-1, including the brain (for example, IGFBP-3). We completed a systematic review of the association between dementia and IGF-1 and IGFBP-3, and a cross-sectional and longitudinal study designed to investigate if lower plasma concentration of these proteins increased the risk of prevalent and incident dementia. A total of 3967 men aged 71-89 years joined the study, of whom 535 (13.5%) showed evidence of prevalent cognitive impairment. The plasma concentrations of IGF-1 and IGFBP-3 were similar for men with and without cognitive impairment. The 3432 men free of cognitive impairment were then followed for up to 13 years. During this time 571 (16.6%) developed dementia. The plasma concentration of IGF-1 had no association with incident dementia. The doubling of the plasma concentration of IGFBP-3 decreased the hazard ratio of dementia by 23% (95% confidence interval=5-37%). The results were not affected by age, body mass index and history of smoking, diabetes, hypertension, coronary heart disease or stroke. If these findings are confirmed by others, the plasma concentration of IGFBP-3 could be used to improve the accuracy of predictive models of dementia and as a potential new factor to assist in the development of prevention and treatment strategies.
Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.
Fink Howard A,Jutkowitz Eric,McCarten J Riley,Hemmy Laura S,Butler Mary,Davila Heather,Ratner Edward,Calvert Collin,Barclay Terry R,Brasure Michelle,Nelson Victoria A,Kane Robert L
Annals of internal medicine
Background:Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain. Purpose:To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI. Data Sources:Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations. Study Selection:English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. Data Extraction:Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy. Data Synthesis:Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism). Limitation:High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication. Conclusion:Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI. Primary Funding Source:Agency for Healthcare Research and Quality.
Development and validation of a brief dementia screening indicator for primary care.
Barnes Deborah E,Beiser Alexa S,Lee Anne,Langa Kenneth M,Koyama Alain,Preis Sarah R,Neuhaus John,McCammon Ryan J,Yaffe Kristine,Seshadri Sudha,Haan Mary N,Weir David R
Alzheimer's & dementia : the journal of the Alzheimer's Association
BACKGROUND:Detection of "any cognitive impairment" is mandated as part of the Medicare annual wellness visit, but screening all patients may result in excessive false positives. METHODS:We developed and validated a brief Dementia Screening Indicator using data from four large, ongoing cohort studies (the Cardiovascular Health Study [CHS]; the Framingham Heart Study [FHS]; the Health and Retirement Study [HRS]; the Sacramento Area Latino Study on Aging [SALSA]) to help clinicians identify a subgroup of high-risk patients to target for cognitive screening. RESULTS:The final Dementia Screening Indicator included age (1 point/year; ages, 65-79 years), less than 12 years of education (9 points), stroke (6 points), diabetes mellitus (3 points), body mass index less than 18.5 kg/m(2) (8 points), requiring assistance with money or medications (10 points), and depressive symptoms (6 points). Accuracy was good across the cohorts (Harrell's C statistic: CHS, 0.68; FHS, 0.77; HRS, 0.76; SALSA, 0.78). CONCLUSIONS:The Dementia Screening Indicator is a simple tool that may be useful in primary care settings to identify high-risk patients to target for cognitive screening.
Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.
Jefferson Angela L,Cambronero Francis E,Liu Dandan,Moore Elizabeth E,Neal Jacquelyn E,Terry James G,Nair Sangeeta,Pechman Kimberly R,Rane Swati,Davis L Taylor,Gifford Katherine A,Hohman Timothy J,Bell Susan P,Wang Thomas J,Beckman Joshua A,Carr John Jeffrey
BACKGROUND:Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults. METHODS:Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 ( APOE ε4) status, and regional tissue volume. Models were repeated testing PWV× APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation. RESULTS:Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (β=-0.43; P=0.04) and higher CVR in the whole brain (β=0.11; P=0.02), frontal lobes (β=0.12; P<0.05), temporal lobes (β=0.11; P=0.02), and occipital lobes (β=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (β=-1.16; P=0.047), lower temporal lobe CBF (β=-1.81; P=0.004), and higher temporal lobe CVR (β=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (β=-0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (β=-1.20; P=0.02). CONCLUSIONS:Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.
Association of Nonalcoholic Fatty Liver Disease With Lower Brain Volume in Healthy Middle-aged Adults in the Framingham Study.
Weinstein Galit,Zelber-Sagi Shira,Preis Sarah R,Beiser Alexa S,DeCarli Charles,Speliotes Elizabeth K,Satizabal Claudia L,Vasan Ramachandran S,Seshadri Sudha
Importance:Nonalcoholic fatty liver disease (NAFLD) is a common condition that is most often asymptomatic. It is associated with metabolic syndrome, incident diabetes, carotid atherosclerosis, and endothelial dysfunction, conditions that in turn are strongly linked with brain damage and cognitive impairment. However, it is not known whether NAFLD is associated with structural brain measures in humans. Objective:To assess the association between prevalent NAFLD and brain magnetic resonance imaging (MRI) measures. Design, Setting, and Participants:The cross-sectional association between NAFLD and brain MRI measures was assessed from November 6, 2002, to March 16, 2011, in 766 individuals from the Offspring cohort of the Framingham Study. Participants were included if they did not have excessive alcohol intake and were free of stroke and dementia. Data analysis was conducted from December 30, 2015, to June 15, 2016. Exposures:Nonalcoholic fatty liver disease was assessed by multidetector computed tomographic scans of the abdomen. Main Outcomes and Measures:Linear or logistic regression models were used to evaluate the cross-sectional association between NAFLD and brain MRI measures, adjusting for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, hypertension, current smoking, high-density lipoprotein and low-density lipoprotein cholesterol levels, lipid treatment, type 2 diabetes, cardiovascular disease, physical activity, insulin resistance, C-reactive protein levels, and plasma homocysteine values. Brain MRI measures included total cerebral brain volume, hippocampal and white matter hyperintensity volumes, and presence or absence of covert brain infarcts. Results:Of the 766 individuals in the study sample (410 women and 356 men; mean [SD] age at the time of brain MRI, 67  years), 137 (17.9%) had NAFLD. Nonalcoholic fatty liver disease was significantly associated with smaller total cerebral brain volume even after adjustment for all the covariates included in the study (β [SE], -0.26 [0.11]; P = .02). Differences in total cerebral brain volume between those with and without NAFLD corresponded to 4.2 years of brain aging in the general sample and to 7.3 years in individuals younger than 60 years of age. No statistically significant associations were observed between NAFLD and hippocampal or white matter hyperintensity volumes or covert brain infarcts. Conclusions and Relevance:Nonalcoholic fatty liver disease is associated with a smaller total cerebral brain volume, independent of visceral adipose tissue and cardiometabolic risk factors, pointing to a possible link between hepatic steatosis and brain aging.
[Case-control study on the influencing factors related to cognitive impairment in the elderly population of China].
Qi S G,Wang Z H,Wei C B,Yang Z,Zhu X Q
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]
To explore the influencing factors affecting the cognitive impairment of the elderly population in China. A stratified multi-stage cluster sampling was used in 6 provinces (autonomous administrative regions and municipalities) to select the sample. A total 24 000 urban and rural residents aged 60 years and above received a set of standardized questionnaire interview, physical examinations, laboratory test of lipid and glucose levels of blood and apolipoprotein E (APOE) genotype. The primary screening of cognitive function was assessed by using the Chinese Version of Ascertain Dementia 8, and then suspicious cognitive impairment cases with more than two abnormal results would receive the further cognitive function assessment by using the Mini-Mental State Examination (MMSE). 1 300 cases with cognitive impairment and 2 600 controls without cognitive impairment were recruited and matched according to their age, gender and resident area in a 1∶2 case-control study. The conditional logistic regression model was used to analyze the association between relevant factors and cognitive impairment. Factors negatively associated with cognitive impairment and their (95) values were primary or middle school as 0.63 (0.51-0.77), high school and above as 0.59 (0.39-0.88), daily neighborhood communication as 0.61 (0.50-0.75), weekly participating in social activities 0.59 (0.44-0.79), daily tea drinking as 0.71 (0.58-0.88) and doing regular exercise as 0.71 (0.57-0.88), reading newspaper (occasional: 0.50 (0.37-0.67); frequent: 0.40 (0.28-0.57)), playing majiang or cards (occasional: 0.51 (0.34-0.74); frequent: 0.50 (0.36-0.68)) respectively. Factors positively associated with cognitive impairment and their (95) values were APOE-ε4 heterozygote as 1.31 (1.08-1.58), homozygote as 2.74 (1.52-5.00), diabetes onset before 50 years of age and after as 9.03 (3.07-33.60) and 4.40 (3.18-6.17), stroke as 1.90 (1.35-2.69), asthma as 1.95 (1.11-3.42) respectively. APOE-ε4 alleles, lower educational level, stroke, asthma, diabetes are risk factors of cognitive impairment in the elderly. Keeping a healthy lifestyle and preventing chronic diseases in the whole life course could significantly reduce the incidence of cognitive impairment in the elderly.
Carotid intima-media thickness is associated with the progression of cognitive impairment in older adults.
Moon Jae Hoon,Lim Soo,Han Ji Won,Kim Kyoung Min,Choi Sung Hee,Park Kyong Soo,Kim Ki Woong,Jang Hak Chul
BACKGROUND AND PURPOSE:We investigated the association between cardiovascular risk factors, including carotid intima-media thickness (CIMT), and future risk of mild cognitive impairment (MCI) and dementia in elderly subjects. METHODS:We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Our study included 348 participants who were nondemented at the baseline (mean age, 71.7±6.3 years) and underwent cognitive evaluation at the 5-year follow-up. Baseline cardiovascular risk factors were compared according to the development of MCI or dementia during the study period. RESULTS:At the baseline evaluation, 278 subjects were cognitively normal and 70 subjects had MCI. Diagnoses of cognitive function either remained unchanged or improved during the study period in 292 subjects (nonprogression group), whereas 56 subjects showed progression of cognitive impairment to MCI or dementia (progression group). The progression group exhibited a higher prevalence of hypertension and greater CIMT compared with the nonprogression group. Other baseline cardiovascular risk factors, including sex, body mass index, diabetes mellitus, insulin resistance, total cholesterol, waist-to-hip ratio, visceral fat, pulse wave velocity, and ankle-brachial index, were not significantly different between 2 groups. The association between greater baseline CIMT and the progression of cognitive impairment was maintained after adjustment for conventional baseline risk factors of cognitive impairment. Greater baseline CIMT was also independently associated with the development of MCI in the subjects whose baseline cognitive function was normal. CONCLUSIONS:Greater baseline CIMT was independently associated with the risk of cognitive impairment, such as MCI and dementia in elderly subjects.
A low ankle-brachial index is associated with cognitive impairment: The APAC study.
Wang Anxin,Jiang Ruixuan,Su Zhaoping,Jia Jiaokun,Zhang Ning,Wu Jianwei,Chen Shengyun,Zhao Xingquan
BACKGROUND AND AIMS:Given the recognized links between atherosclerosis and cognitive impairment, the aim of this study was to examine the association between the ankle-brachial index (ABI) and cognitive impairment in a cross-sectional setting of a Chinese population. METHODS:Participants (n = 3,048, aged ≥40 years, 1727 men and 1321 women) were recruited from the ongoing community-based Asymptomatic Polyvascular Abnormalities Community Study. ABI was measured and a low ABI was defined as <0.9. Cognition status was evaluated via the Mini-Mental Status Exam. Multivariate logistic regression models and linear regression models were used to assess the association between ABI and cognitive impairment. RESULTS:A low ABI was associated with cognitive impairment (odds ratio, OR = 1.983; 95% confidence interval, CI: 1.150-3.419), independent of the potential confounders. In addition, a decreasing ABI (per standard deviation) was significantly associated with cognitive impairment in fully adjusted models (OR = 1.156; CI: 1.013-1.319) and with a significant trend of decreasing MMSE scores (β = 0.703, 95% CI 0.189-1.218, p = 0.0074). Furthermore, the odds of a low ABI associated with cognitive impairment in participants without hypertension and participants with diabetes were 4.924 (CI: 1.860-13.035) and 6.393 (CI: 2.431-16.810), respectively. CONCLUSIONS:A low ABI is associated with cognitive impairment, especially in non-hypertensive and diabetic patients.
Influence of cerebral white matter hyperintensities on cognitive impairment in elderly medical patients.
Shibata Koichi,Nishimura Yoshiko,Otsuka Kuniaki,Sakura Hiroshi
Geriatrics & gerontology international
AIM:We investigated the characteristics of elderly medical patients with white matter hyperintensities on magnetic resonance imaging. METHODS:A total of 213 patients (123 men and 90 women; mean age 74.8 years) reported their history of hypertension, diabetes, dyslipidemia, previous stroke, coronary heart disease and chronic kidney disease (CKD). All patients completed the Mini-Mental State Examination and Geriatric Depression Scale. White matter hyperintensities were evaluated for the periventricular region, basal ganglia (BGH), deep white matter and infratentorial region, and brain atrophy was calculated as bicaudate ratios. RESULTS:Patients with cognitive impairment (Mini-Mental State Examination score < 24) were significantly older (P = 0.001), had periventricular region hyperintensities (P = 0.029) and BGH (P = 0.0015), and showed atrophy (P < 0.0001). Logistic regression showed that cognitive impairment was predicted by stroke (OR 2.5, 95% CI 0.033-0.894, P = 0.036) and atrophy (OR 8.43, 95% CI 5.71-37.0, P = 0.0109). Multiple regressions showed that BGH was associated with CKD (β = 0.213; P = 0.003), and infratentorial region was associated with stroke (β = 0.157; P =0.035) and CKD (β = 0.172; P = 0.016). Periventricular region was associated with age (β = 0.2; P = 0.011) and Geriatric Depression Scale (β = 0.151; P = 0.037), and deep white matter hyperintensities with age (β = 0.189; P = 0.016). CONCLUSIONS:Although cognitive impairment in elderly medical patients is associated with stroke and brain atrophy, white matter hyperintensities, especially BGH and infratentorial region, are associated with cognitive decline in relation to CKD. Geriatr Gerontol Int 2017; 17: 1488-1493.
Correlates of Dementia and Mild Cognitive Impairment in Patients With Atrial Fibrillation: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).
Alonso Alvaro,Knopman David S,Gottesman Rebecca F,Soliman Elsayed Z,Shah Amit J,O'Neal Wesley T,Norby Faye L,Mosley Thomas H,Chen Lin Y
Journal of the American Heart Association
BACKGROUND:Atrial fibrillation (AF) has been associated with faster cognitive decline and increased dementia risk. Factors associated with dementia in patients with AF have been seldom studied. METHODS AND RESULTS:We studied 6432 individuals from the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). In 2011 to 2013, participants underwent a physical exam, echocardiography, detailed cognitive assessments, and a subset, brain magnetic resonance imaging. Dementia and mild cognitive impairment (MCI), as well as etiology of MCI/dementia, Alzheimer's disease-related or vascular, were adjudicated by an expert panel. AF was defined by study ECGs and past hospitalizations. We used logistic regression to estimate odds ratios and 95% CI of MCI/dementia by AF status and to assess cross-sectional correlates of MCI/dementia in patients with AF. Among 6432 participants, 611 (9.5%) had prevalent AF. AF was associated with increased odds of dementia and MCI (odds ratio, 95% CI, 2.25, 1.64-3.10, and 1.28, 1.04-1.56, respectively). Prevalence of Alzheimer's disease-related MCI/dementia and vascular MCI/dementia were higher in participants with AF than without AF (odds ratio, 95% CI, 1.29, 1.04-1.61, and 1.50, 0.99-2.25, respectively). In multivariable analyses, older age, lower body mass index, diabetes mellitus, stroke, and genotype were associated with dementia prevalence in participants with AF. In models evaluating MCI/dementia subtypes, diabetes mellitus was associated with Alzheimer's disease-related MCI/dementia, whereas male sex and stroke were risk factors for vascular MCI/dementia. CONCLUSIONS:In a large, community-based study, AF was associated with higher prevalence of MCI and dementia. Controlling cardiometabolic risk factors is a potential target for prevention of adverse cognitive outcomes in AF patients.
Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus.
Sonoda Mika,Shoji Tetsuo,Kuwamura Yukinobu,Okute Yujiro,Naganuma Toshihide,Shima Hideaki,Motoyama Koka,Morioka Tomoaki,Mori Katsuhito,Fukumoto Shinya,Shioi Atsushi,Shimono Taro,Fujii Hisako,Kabata Daijiro,Shintani Ayumi,Emoto Masanori,Inaba Masaaki
Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.
FGF21 Attenuates High-Fat Diet-Induced Cognitive Impairment via Metabolic Regulation and Anti-inflammation of Obese Mice.
Wang Qingzhi,Yuan Jing,Yu Zhanyang,Lin Li,Jiang Yinghua,Cao Zeyuan,Zhuang Pengwei,Whalen Michael J,Song Bo,Wang Xiao-Jie,Li Xiaokun,Lo Eng H,Xu Yuming,Wang Xiaoying
Accumulating studies suggest that overnutrition-associated obesity may lead to development of type 2 diabetes mellitus and metabolic syndromes (MetS). MetS and its components are important risk factors of mild cognitive impairment, age-related cognitive decline, vascular dementia, and Alzheimer's disease. It has been recently proposed that development of a disease-course modification strategy toward early and effective risk factor management would be clinically significant in reducing the risk of metabolic disorder-initiated cognitive decline. In the present study, we propose that fibroblast growth factor 21 (FGF21) is a novel candidate for the disease-course modification approach. Using a high-fat diet (HFD) consumption-induced obese mouse model, we tested our hypothesis that recombinant human FGF21 (rFGF21) administration is effective for improving obesity-induced cognitive dysfunction and anxiety-like behavior, by its multiple metabolic modulation and anti-pro-inflammation actions. Our experimental findings support our hypothesis that rFGF21 is protective to HFD-induced cognitive impairment, at least in part by metabolic regulation in glucose tolerance impairment, insulin resistance, and hyperlipidemia; potent systemic pro-inflammation inhibition; and improvement of hippocampal dysfunction, particularly by inhibiting pro-neuroinflammation and neurogenesis deficit. This study suggests that FGF21 might be a novel molecular target of the disease-course-modifying strategy for early intervention of MstS-associated cognitive decline.
A Review of Risk Factors for Cognitive Impairment in Stroke Survivors.
Mohd Zulkifly Mohd Faizal,Ghazali Shazli Ezzat,Che Din Normah,Singh Devinder Kaur Ajit,Subramaniam Ponnusamy
In this review, we aimed to identify the risk factors that may influence cognitive impairment among stroke survivors, namely, demographic, clinical, psychological, and physical determinants. A search from Medline, Scopus, and ISI Web of Science databases was conducted for papers published from year 2004 to 2015 related to risk factors of cognitive impairment among adult stroke survivors. A total of 1931 articles were retrieved, but only 27 articles met the criteria and were reviewed. In more than half of the articles it was found that demographical variables that include age, education level, and history of stroke were significant risk factors of cognitive impairment among stroke survivors. The review also indicated that diabetes mellitus, hypertension, types of stroke and affected region of brain, and stroke characteristics (e.g., size and location of infarctions) were clinical determinants that affected cognitive status. In addition, the presence of emotional disturbances mainly depressive symptoms showed significant effects on cognition. Independent relationships between cognition and functional impairment were also identified as determinants in a few studies. This review provided information on the possible risk factors of cognitive impairment in stroke survivors. This information may be beneficial in the prevention and management strategy of cognitive impairments among stroke survivors.
Association between Metabolic Syndrome and Cognitive Impairment after Acute Ischemic Stroke: A Cross-Sectional Study in a Chinese Population.
Li Pan,Quan Wei,Lu Da,Wang Yan,Zhang Hui-Hong,Liu Shuai,Jiang Rong-Cai,Zhou Yu-Ying
BACKGROUND AND OBJECTIVES:Metabolic syndrome (MetS), a risk factor for many vascular conditions, is associated with vascular cognitive disorders. The objective of the present study was to explore the associations of MetS and its individual components with the risks of cognitive impairment and neurological dysfunction in patients after acute stroke. METHODS:This cross-sectional study enrolled 840 patients ranging in age from 53 to 89 years from the Tianjin area of North China. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination. Neuropsychiatric behavior was assessed using the Neuropsychiatric Inventory Questionnaire. Emotional state was examined according to the Hamilton Depression Rating Scale, and neuromotor function was evaluated using the National Institutes of Health Stroke Scale, Barthel index, and the Activity of Daily Living test. After overnight fasting, blood samples were obtained to measure biochemistry indicators. RESULTS:MetS and its individual components were closely correlated with MoCA score. MetS patients had high levels of inflammation and a 3.542-fold increased odds ratio (OR) for cognitive impairment [95% confidence interval (CI): 1.972-6.361]. Of the individual MetS components, central obesity (OR 3.039; 95% CI: 1.839-5.023), high fasting plasma glucose (OR 1.915; 95% CI: 1.016-3.607), and type 2 diabetes (OR 2.241; 95% CI: 1.630-3.081) were associated with an increased incidence of cognitive impairment. Consistent and significant worsening in different neurological domains was observed with greater numbers of MetS components. CONCLUSIONS:MetS was associated with worse cognitive function, neuromotor dysfunction, and neuropsychological symptoms among Chinese acute stroke patients.
Cognitive impairment and postural control deficit in adults with Type 2 diabetes.
Gorniak Stacey L,Lu Fangmei Yoshimi,Lee Beom Chan,Massman Paul J,Wang Jing
Diabetes/metabolism research and reviews
BACKGROUND:Diseases induced by metabolic disorders, eg, Type 2 diabetes, has recently been linked to both sensory and motor deficit in the absence of a formal clinical diagnosis of peripheral neuropathy. Studies have demonstrated mild cognitive impairment in diabetic patients, which also plays a role in one's loss of ability to successfully perform basic motor activities. This project focused on evaluating cognitive function while maintaining balance. We hypothesized that simultaneous cognitive and motor deficit would occur among adults with Type 2 diabetes versus healthy age- and sex-matched control during a balance task. METHODS:A sample of 10 Type 2 diabetes patients and 10 age-matched and sex-matched controls underwent a series of sensory, motor, cognitive, and cognitive-motor evaluations. Blood pressure and A levels were assessed. RESULTS:Significantly lower cognitive function scores, particularly in the domain of working memory, were exhibited in the diabetic group than controls. Balance in the diabetic group was overall poorer in both single- and dual-tasks than controls. When diabetic patients were asked to verbally recall different words while maintaining their balance, their accuracy rate was significantly lower than controls. Some health state measures were found to co-vary with motor function. Increased body mass index in the diabetic group did not account for motor function deficit. SIGNIFICANCE:Our data suggest that: (1) systemic deficit beyond tactile dysfunction and increased body mass index contribute to reduced motor function in diabetes, and (2) both balance and working memory functions are simultaneously impaired in patients with Type 2 diabetes.
Vascular risk factors aggravate cognitive impairment in first-ever young ischaemic stroke patients.
Lu D,Ren S,Zhang J,Sun D
European journal of neurology
BACKGROUND AND PURPOSE:Young ischaemic stroke patients often suffer from cognitive impairment after stroke. However, the risk factors of cognitive impairment are still unclear. This study examined the impact of vascular risk factors (VRFs) on cognitive impairment in first-ever young ischaemic stroke patients. METHODS:Subjects were divided into low (0-1 VRF, n = 27), medium (2-3 VRFs, n = 45) and high-risk (≥4 VRFs, n = 12) groups according to their number of VRFs. The following VRFs were collected: hypertension, diabetes mellitus, dyslipidaemia, atrial fibrillation, obesity, smoking, excess alcohol consumption, coronary heart disease and hyperhomocysteinaemia. A battery of cognitive assessments was executed 2 weeks after stroke. Differences of cognitive performances between groups were compared. The correlation between VRFs and cognitive function was investigated with an emphasis on discovering the main VRFs. RESULTS:Eighty-four patients were enrolled in this study eventually. Compared with the low-risk group, the high-risk group had significantly worse performance in most of the cognitive domains. VRFs had a correlation with general cognition, executive function, attention and verbal fluency. After adjusting the covariates, VRFs showed a linear correlation with global cognitive function (R = 0.640, P = 0.000), verbal fluency (R = 0.372, P = 0.000), delayed memory (R = 0.327, P = 0.002), visual attention (R = 0.290, P = 0.007) and executive function (R = 0.266, P = 0.015). Amongst all the VRFs, hypertension, hyperlipidaemia, smoking and hyperhomocysteinaemia were the main influencing VRFs. CONCLUSION:Vascular risk factors aggravate cognitive impairment after young ischaemic stroke. Effective management of VRFs in young adults is urgent and this may reduce the cognitive impairment.
Risk factors for developing dementia in type 2 diabetes mellitus patients with mild cognitive impairment.
Albai Oana,Frandes Mirela,Timar Romulus,Roman Deiana,Timar Bogdan
Neuropsychiatric disease and treatment
Background:Dementia and cognitive dysfunction have many causes. There is strong evidence that diabetes mellitus (DM) increases the risk of cognitive impairment and dementia. Optimal glycemic control, identification of diabetic risk factors, and prophylactic approach are essential in the prevention of cognitive complications. Aims:The main purpose of this study was to establish the cognitive impairment in DM patients, cared for in the Diabetes Center from Timisoara. Also, we investigated the prevalence of dementia in our group as well as the risk factors involved in the progression of mild cognitive impairment (MCI) to dementia. Patients and methods:We considered a sample of 207 type 2 DM (T2DM) patients, aged between 33 and 81 years, mean 57.49 (±11.37) years. We established the diagnosis of dementia based on the Mini-Mental State Examination (MMSE) test, as well as on the psychological testing, psychiatric and neurological investigations, and imaging tests (computerized tomography and MRI). Results:A percentage of 42.03% of patients presented MCI, mean age 63 (57.00-71.00) years, being older than patients without MCI, mean age 52.00 (45.00-61.00) years, <0.001. We observed that diabetes duration was a significant risk factor for developing dementia. Also, patients with MCI presented higher values of body fat than patients without MCI. Moreover, we found that glucose levels, low-density lipoprotein cholesterol levels, the presence of stroke events, and the presence of cardiovascular disease were significant risk factors for MCI conversion to dementia. Conclusion:Patients with T2DM at early to severe stages of MCI are more likely to develop dementia and should be regularly evaluated for their cognitive status. Regular administrations of the MMSE test can be done to detect early stages of MCI development. Also, to reduce the progression of cognitive impairment to dementia, it is worthwhile to give greater importance to glycemic control and overall DM management.
Depression, Type 2 Diabetes, and Poststroke Cognitive Impairment.
Swardfager Walter,MacIntosh Bradley J
Neurorehabilitation and neural repair
Background Ten percent of stroke survivors develop dementia, which increases to more than a third after recurrent stroke. Other survivors develop less severe vascular cognitive impairment. In the general population, depression, and diabetes interact in predicting dementia risk, and they are both prevalent in stroke. Objective To assess the cumulative association of comorbid depressive symptoms and type 2 diabetes with cognitive outcomes among stroke survivors. Methods Multicenter observational cohort study of people within 6 months of stroke. Depression and cognitive status were screened using the Center for Epidemiological Studies Depression (CES-D) scale and the Montreal Cognitive Assessment (MoCA), respectively. Processing speed, executive function and memory were assessed using the Trail Making Test parts A and B, and the 5 Word Delayed Free Recall task. Results Among 342 participants (age 67.0 ± 13.5 years, 43.3% female, 46 ± 35 days poststroke), the prevalence of type 2 diabetes was 32.2% and depressive symptoms (CES-D ≥16) were found in 40.6%. Diabetes and depressive symptoms increased the risk of severe cognitive impairment (MoCA <20) with adjusted odds ratio (OR) 2.12 (95% confidence interval [CI] 1.20-3.74, P = .010) for 1 comorbidity and OR 3.18 (95% CI 1.26-8.02, P = .014) for both comorbidities. Associated cognitive deficits included executive function (F = 3.43, P = .035) but not processing speed (F = 1.86, P = .16) or memory (F = 0.82, P = .44). Conclusions Diabetes and depressive symptoms were associated cumulatively with poorer cognitive screening outcomes poststroke, particularly deficits in executive function. Having 1 comorbidity doubled the odds of screening for severe cognitive impairment, having both tripled the odds.