Journal of Alzheimer's Disease - Volume 70, issue s1

Authors: Anstey, Kaarin J. | Peters, Ruth

Article Type: Editorial

DOI: 10.3233/JAD-190506

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S1-S3, 2019

Authors: Glymour, M. Maria | Whitmer, Rachel A.

Article Type: Editorial

DOI: 10.3233/JAD-190304

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S5-S10, 2019

Authors: Brayne, Carol | Richard, Edo

Article Type: Editorial

DOI: 10.3233/JAD-190448

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S11-S14, 2019

Authors: Sexton, Claire E. | Yaffe, Kristine

Article Type: Editorial

DOI: 10.3233/JAD-190104

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S15-S17, 2019

Authors: Sacre, Julian W. | Magliano, Dianna J. | Zimmet, Paul Z. | Polkinghorne, Kevan R. | Chadban, Steven J. | Anstey, Kaarin J. | Shaw, Jonathan E.

Article Type: Research Article

Abstract: Background: The role of chronic kidney disease (CKD) as a risk factor for cognitive impairment independent of their shared antecedents remains controversial. Objective: To determine whether kidney damage (indicated by albuminuria) or kidney dysfunction (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 ) predict future (12-year) cognitive function independently of their shared risk factors. Methods: We studied 4,128 individuals from the 1999/00 population-based Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study who returned in 2011/12 for follow-up cognitive function testing. Albuminuria was defined by urinary albumin:creatinine≥3.5 (women) or≥2.5 mg/mmol (men). Kidney dysfunction was indicated by eGFR <60 ml/min/1.73 m2 . Cognitive function …domains assessed included memory (California Verbal Learning Test [CVLT]) and processing speed (Symbol Digit Modalities Test [SDMT]). Results: Baseline albuminuria and kidney dysfunction were identified in 142 (3.4%) and 39 (0.9%) individuals, respectively, with minimal overlap (n  = 7). Those with albuminuria demonstrated concurrently reduced 12-year SDMT (p  = 0.084) and CVLT scores (p  = 0.005) following adjustment for age, sex, and education. However, only CVLT performance remained worse (p  = 0.027) following additional adjustment for myocardial infarction, stroke, and related risk factors (hypertension, diabetes, dyslipidemia, smoking, BMI, physical activity, and alcohol intake). Indeed, these collective covariates were responsible for 47% of the effect of albuminuria on SDMT, but only 21% of its effect on CVLT. Kidney dysfunction was not associated with either SDMT or CVLT performance (p  > 0.10). Conclusions: Albuminuria predicted worse memory function at 12 years follow-up, whereas its effect on processing speed was driven largely by differences in cardiovascular risk. Kidney dysfunction based on eGFR predicted neither cognitive domain. Show more

Keywords: Cardiovascular diseases, cognition disorders, cognitive decline, cognitive impairment, cohort studies, kidney diseases

DOI: 10.3233/JAD-180498

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S19-S30, 2019

Authors: Deckers, Kay | Nooyens, Astrid | van Boxtel, Martin | Verhey, Frans | Verschuren, Monique | Köhler, Sebastian

Article Type: Research Article

Abstract: Background: Several modifiable risk factors for cognitive decline have been identified, but whether differences by gender and educational level exist is unclear. Objective: The present study aims to clarify this by prospectively investigating the relationship between health and lifestyle factors and cognitive functioning in different subgroups defined by gender and educational level. Methods: 2,347 cognitive healthy individuals (mean age = 54.8, SD = 6.8, range: 41–71; 51.8% female; 26.2% low education) from the Doetinchem Cohort Study were examined for cognitive function at baseline, and at 5- and 10-year follow-up. Health- and lifestyle factors were captured by a poly-environmental risk score …labelled ‘LIfestyle for BRAin Health’ (LIBRA). This score consists of 12 modifiable risk and protective factors for cognitive decline and dementia, with higher scores indicating greater risk (range: –2.7 to +12.7). Heterogeneity in associations between LIBRA and decline in verbal memory, cognitive flexibility, and mental speed between males and females and individuals with different levels of education were assessed in linear mixed models. Results: Overall, higher LIBRA scores predicted faster decline in verbal memory, cognitive flexibility, and mental speed over 10 years. Higher LIBRA scores were further associated with increased risk for incident cognitive impairment (one-point increase in LIBRA: HR = 1.09, 1.04–1.14, p  = 0.001). In general, these effects were similar across gender and educational level. Conclusion: A composite risk score comprising unhealthy lifestyle and relatively poor health in midlife is significantly associated with a worse course of cognition 10 years later. These associations were for the most part unrelated to gender or educational differences. Show more

Keywords: Aging, cognition, dementia, education, gender, lifestyle, modifiable risk factors, prevention

DOI: 10.3233/JAD-180492

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S31-S41, 2019

Authors: Abu Bakar, Zulzikry Hafiz | Damanhuri, Hanafi Ahmad | Makpol, Suzana | Wan Kamaruddin, Wan Mohd Aizat | Abdul Sani, Nur Fathiah | Amir Hamzah, Ahmad Imran Zaydi | Nor Aripin, Khairun Nain | Mohd Rani, Mohd Dzulkhairi | Noh, Nor Azila | Razali, Rosdinom | Mazlan, Musalmah | Abdul Hamid, Hamzaini | Mohamad, Mazlyfarina | Wan Ngah, Wan Zurinah

Article Type: Research Article

Abstract: Background: Many studies on biochemical and psychological variables have aimed to elucidate the association between aging and cognitive function. Demographic differences and protein expression have been reported to play a role in determining the cognitive capability of a population. Objective: This study aimed to determine the effect of age on the protein profile of Malay individuals and its association with cognitive competency. Methods: A total of 160 individuals were recruited and grouped accordingly. Cognitive competency of each subject was assessed with several neuropsychological tests. Plasma samples were collected and analyzed with Q Exactive HF Orbitrap. Proteins …were identified and quantitated with MaxQuant and further analyzed with Perseus to determine differentially expressed proteins. PANTHER, Reactome, and STRING were applied for bioinformatics output. Results: Our data showed that the Malay individuals are vulnerable to the deterioration of cognitive function with aging, and most of the proteins were differentially expressed in concordance. Several physiological components and pathways were shown to be involved, giving a hint of a promising interpretation on the induction of aging toward the state of the Malays’ cognitive function. Nevertheless, some proteins have shown a considerable interaction with the generated protein network, which provides a direction of focus for further investigation. Conclusion: This study demonstrated notable changes in the expression of several proteins as age increased. These changes provide a promising platform for understanding the biochemical factors affecting cognitive function in the Malay population. The exhibited network of protein-protein interaction suggests the possibility of implementing regulatory intervention in ameliorating Malay cognitive function. Show more

Keywords: Aging, cognitive function, Malay population, protein profiling

DOI: 10.3233/JAD-180511

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S43-S62, 2019

Authors: Cherbuin, Nicolas | Walsh, Erin I. | Prina, A. Matthew

Article Type: Research Article

Abstract: Background: Chronic obstructive pulmonary disease (COPD) is a major disease burden which accounts for 5% of all deaths globally, with most of those (>90%) occurring in lower to middle income countries (LMIC). It is also emerging as an important modifiable dementia risk factor. Objective: To address the knowledge gap surrounding the nature of the associations between COPD, dementia, and mortality, and the geographical variation of those associations in LMIC. Methods: Data from the 10/66 study surveying 15,394 participants (mean age 74 years, 62% female) across 8 countries was used to estimate the prevalence of self-reported COPD …and its association with incident dementia and premature death. Proportional sub-hazards models using a cumulative incidence function were applied to identify the probability of incident dementia onset given the risk of premature death, with estimates pooled across countries via random effect meta-analysis. Results: Over the 3-year follow-up, almost 10% of participants developed dementia and 14% were deceased. COPD was not significantly associated with dementia incidence except in Cuba. However, fully adjusted models indicated that individuals with COPD were at a 28% increased risk of premature death, a trend present across most countries when analyzed individually. Conclusion: The link between COPD and dementia is currently somewhat different and weaker in LMIC than in developed countries. This may be because premature death in the populations studied mask the development of clinical dementia. Given the global trend toward increased life expectancy, it is critical that the disease burden associated with COPD be addressed without delay if a further rise in dementia prevalence associated with COPD is to be avoided in LMIC. Show more

Keywords: Chronic obstructive pulmonary disease, lower to middle income countries, mild cognitive impairment, premature death, prevalence

DOI: 10.3233/JAD-180562

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S63-S73, 2019

Authors: Radford, Kylie | Lavrencic, Louise M. | Delbaere, Kim | Draper, Brian | Cumming, Robert | Daylight, Gail | Mack, Holly A. | Chalkley, Simon | Bennett, Hayley | Garvey, Gail | Hill, Thi Yen | Lasschuit, Danielle | Broe, Gerald A.

Article Type: Research Article

Abstract: Dementia prevalence in Aboriginal and Torres Strait Islander Australians is three to five times higher than the general Australian population. A better understanding of the underlying biomedical and social risk factors is needed to guide dementia prevention in Aboriginal Australians. The current study is the first to examine potential risk factors for dementia in the majority urban and regional population, with a representative sample of 336 Aboriginal Australians aged 60 years and older. Participants included 45 people with a dementia diagnosis (n  = 27 probable/possible Alzheimer’s disease); and 286 people without dementia. Univariate logistic regression analyses (controlling for age) identified childhood …trauma, mid-life factors (history of unskilled work, past high-risk alcohol use), and medical factors (history of stroke, head injury with loss of consciousness, epilepsy) as risk factors for dementia. Multivariable analysis revealed age, childhood trauma, unskilled work, stroke, and head injury as independent predictors of all-cause dementia. A range of comorbid factors related to dementia was also identified (i.e., functional impairment, incontinence, recent hospital admission, low body mass index, living in residential care, depression, current high-risk alcohol use, social isolation, low physical activity levels). These findings extend previous outcomes in a remote Aboriginal population by highlighting that life-course social determinants of health, in addition to neurological disorders, likely play an important role in elevating dementia risk. Certain psychosocial and medical exposures are highly prevalent in Aboriginal Australians, similar to other indigenous populations, and should be considered when designing targeted and culturally appropriate prevention initiatives to reduce the burden of dementia. Show more

Keywords: Aged, Alzheimer’s disease, indigenous population, neurocognitive disorders, social determinants of health

DOI: 10.3233/JAD-180573

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S75-S85, 2019

Authors: Danat, Isaac M. | Clifford, Angela | Partridge, Martin | Zhou, Weiju | Bakre, Aishat T. | Chen, Anthony | McFeeters, Danielle | Smith, Tina | Wan, Yuhui | Copeland, John | Anstey, Kaarin J. | Chen, Ruoling

Article Type: Research Article

Abstract: Background: It is unclear whether overweight and obesity in older age reduces or increases the risk of incident dementia. Objective: To assess the impacts of overweight and obesity in older age on incident dementia. Methods: We searched cohort studies reporting body weight measured in older age and dementia through PubMed, Embase, Medline, PyschInfo, and Cochrane library until July 2016. Sixteen articles were identified for the review. We pooled data from them and a new unpublished study from China, to calculate relative risk (RR) of incident dementia in relation to body mass index (BMI) and waist circumference …(WC). Results: All 16 cohort studies were undertaken in high income countries, with follow-up periods ranging between 3 to 18 years. Thirteen studies showed an inverse association between BMI and dementia, and three studies demonstrated a positive association. Pooled RR of dementia in relation to continuous BMI from 14 studied populations, including the new Chinese data, was 0.97 (95% CI 0.95–1.00); in those followed up <9 years it was 0.95 (0.93–0.96) while in ≥9 years follow-up it was 1.03 (0.96–1.11). In five studied populations examining categorical BMI, RR of dementia in older people classified as overweight and obese was 0.98 (0.54–1.77) and 1.17 (0.65–2.10) respectively, in comparison with other weights. The pooled WC data showed no association between increased WC and reduced risk of dementia. Conclusion: The current evidence did not support a paradox on beneficial impacts of overweight and obesity in older age on incident dementia. More studies with long term follow up are needed to clarify the association of body weight in older age with dementia risk. Show more

Keywords: Body weight, dementia, meta-analysis, older people

DOI: 10.3233/JAD-180763

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S87-S99, 2019