Background
Despite the well‐established link between type 2 diabetes and dementia, its impact on the prodromal dementia phase remains controversial, as does the impact of comorbid cardiovascular ...disease (CVD). In this study, we assessed the impact of diabetes and CVD on the development of cognitive impairment no dementia (CIND) and its progression to dementia.
Methods
In the Swedish National Study on Aging and Care‐Kungsholmen (SNAC‐K), a cohort of cognitively‐intact individuals (n=1840) and a cohort of individuals with CIND (n=682) aged ≥60 years were followed over 15 years. At baseline and each follow‐up (every 3 or 6 years), a neuropsychological test battery was administered to assess five cognitive domains (episodic memory, processing speed, executive function, verbal fluency, visuospatial abilities). CIND was defined as having no dementia and cognitive performance ≥1.5 SDs below age group‐specific means in at least one domain. Dementia was diagnosed according to international criteria. Diabetes (controlled and uncontrolled: HbA1c <7.5% vs. ≥7.5%) was assessed based on medical history, clinical records, and glycated hemoglobin. CVD (atrial fibrillation, heart failure, ischemic heart disease, cardiac valve diseases, and bradycardias) was ascertained through medical examinations and medical records. Data were analyzed with multivariable Cox regression models.
Results
At baseline, 135 (7%) participants in the cognitively‐intact cohort and 85 (12%) in the CIND cohort had diabetes. During follow‐up (mean 9.2 ± 3.1 years 2.2–15.6 years), 544 (30%) participants in the cognitively‐intact cohort developed CIND. Diabetes was associated with a 35% higher risk of CIND (HR 1.35, 95% CI: 0.98‐1.88) compared to the diabetes‐free group. This risk rose to 75% in people with comorbid diabetes and CVD (HR 1.75, 95% CI: 1.01‐3.04) and was doubled in people with uncontrolled diabetes (HR 1.97, 95% CI: 1.12‐3.49). In the CIND cohort, 151 (22%) individuals progressed to dementia during follow‐up. Participants with uncontrolled diabetes had triple the risk of progressing to dementia (HR 3.00, 95% CI: 1.26‐7.13) vs. the diabetes‐free group, and the HR of dementia was 4.36 (95% CI: 1.51‐12.59) in individuals with uncontrolled diabetes and comorbid CVD.
Conclusions
Uncontrolled diabetes increases the risk of cognitive impairment and accelerates its progression to dementia, particularly in older adults with comorbid CVD.
Abstract
Background
Cognitive deficits can occur years or even decades before a clinical diagnosis of dementia, with a rate of decline which differs from that in normal aging. This study aimed to ...investigate differences in trajectories of cognitive decline in multiple cognitive domains in the preclinical dementia phase, and whether early rates of decline can be used to predict dementia.
Method
Repeated neuropsychological assessments were conducted for 1652 participants (age ≥60 years) from the Swedish National Study on Aging and Care–Kungsholmen (SNAC‐K). In this sample, 220 developed dementia and 1432 remained dementia free or died without dementia over 12 years. Piecewise linear mixed models were used to compare rates of cognitive decline between people who developed dementia and those who remained dementia free. Individual rates of decline from baseline over six years follow‐up were extrapolated from the mixed models for episodic memory, semantic memory, verbal fluency, and perceptual speed. Fast decliners were identified as those whose rate of decline was >1.5SDs faster than the mean of the no‐dementia group. Multinomial logistic regressions were used to estimate the association between domain‐specific rate of decline and dementia at 9 or 12 year.
Result
Significantly faster decline was observed in all cognitive domains in those who developed dementia vs. those who did not. In piecewise linear mixed‐models, participants in a preclinical dementia phase showed disproportionally accelerated decline as they neared the time of diagnosis in all cognitive domains except episodic memory, where decline was more linear. Being a fast decliner was associated with increased dementia risk and being a fast decliner in at least two cognitive domains further increased the risk of dementia. For the individual domains, however, only rate of decline in verbal fluency added independent variance above that of baseline scores.
Conclusion
The preclinical dementia phase is associated with accelerated cognitive decline, especially in the last 6 years prior to diagnosis. Using early rates of decline (12‐6 years before diagnosis) add some information in the prediction of future dementia and can help identify individuals at increased risk of developing the disease.
Abstract
Background
Despite the well‐established link between type 2 diabetes and dementia, its impact on the prodromal dementia phase remains controversial, as does the impact of comorbid ...cardiovascular disease (CVD). In this study, we assessed the impact of diabetes and CVD on the development of cognitive impairment no dementia (CIND) and its progression to dementia.
Methods
In the Swedish National Study on Aging and Care‐Kungsholmen (SNAC‐K), a cohort of cognitively‐intact individuals (n=1840) and a cohort of individuals with CIND (n=682) aged ≥60 years were followed over 15 years. At baseline and each follow‐up (every 3 or 6 years), a neuropsychological test battery was administered to assess five cognitive domains (episodic memory, processing speed, executive function, verbal fluency, visuospatial abilities). CIND was defined as having no dementia and cognitive performance ≥1.5 SDs below age group‐specific means in at least one domain. Dementia was diagnosed according to international criteria. Diabetes (controlled and uncontrolled: HbA1c <7.5% vs. ≥7.5%) was assessed based on medical history, clinical records, and glycated hemoglobin. CVD (atrial fibrillation, heart failure, ischemic heart disease, cardiac valve diseases, and bradycardias) was ascertained through medical examinations and medical records. Data were analyzed with multivariable Cox regression models.
Results
At baseline, 135 (7%) participants in the cognitively‐intact cohort and 85 (12%) in the CIND cohort had diabetes. During follow‐up (mean 9.2 ± 3.1 years 2.2–15.6 years), 544 (30%) participants in the cognitively‐intact cohort developed CIND. Diabetes was associated with a 35% higher risk of CIND (HR 1.35, 95% CI: 0.98‐1.88) compared to the diabetes‐free group. This risk rose to 75% in people with comorbid diabetes and CVD (HR 1.75, 95% CI: 1.01‐3.04) and was doubled in people with uncontrolled diabetes (HR 1.97, 95% CI: 1.12‐3.49). In the CIND cohort, 151 (22%) individuals progressed to dementia during follow‐up. Participants with uncontrolled diabetes had triple the risk of progressing to dementia (HR 3.00, 95% CI: 1.26‐7.13) vs. the diabetes‐free group, and the HR of dementia was 4.36 (95% CI: 1.51‐12.59) in individuals with uncontrolled diabetes and comorbid CVD.
Conclusions
Uncontrolled diabetes increases the risk of cognitive impairment and accelerates its progression to dementia, particularly in older adults with comorbid CVD.
Background
Dementia is the end‐product of decades of accumulating neuropathology. Resilience mechanisms can help sustaining the brain structure (brain maintenance, BM) and/or compensating for ...neuropathology (cognitive reserve, CR), preserving cognition. Measuring such mechanisms, however, has been challenging with traditional approaches as they fail to capture the complex biological dimension. Using deep learning (DL), we recently developed a biological measure of brain age from raw brain MRI images. Here, we tested whether differences between predicted brain age and the chronological age (PBA‐CA) can be used as marker of BM/CR following the latest framework from the NIH‐supported Collaboratory on Research Definitions for Reserve and Resilience.
Method
Within the Gothenburg H70‐Birth cohort 1944, we included 728 septuagenarians with available brain MRI and without cognitive impairments/neuropsychiatric disorders. We applied the DL algorithm (developed in 15115 healthy individuals from four other cohorts) to the participants’ MRI images to predict brain age and compute PBA‐CA, which was categorized in 4 groups according to distribution: Q1 (younger‐appearing brain) to Q4 (older‐appearing brain). Brain pathology included measures of Alzheimer‐neurodegeneration (average cortical thickness in signature areas), small vessel disease (SVD, i.e. presence of lacunes, microbleeds, white‐matter lesions, perivascular spaces), and microstructural white‐matter changes. A global cognitive score was generated by averaging z‐scores from ten tests. Sex‐adjusted regressions were used in data analysis.
Result
Participants with younger‐appearing brains (reference=older‐appearing) were more likely to have less SVD burden (reference: ≥2 SVD; OR=2.75 95% CI 1.41–5.37 for no‐SVD; OR=2.55 95% CI 1.20–5.45 for one‐SVD), white‐matter microstructural alterations, or AD‐related atrophy. Younger‐appearing brains were also associated with better cognitive performance (β‐coefficient=0.19 95% CI 0.04–0.30).
Conclusion
Preliminary findings indicate that negative differences between PBA and CA (PBA<CA) were associated with less AD‐ and cerebrovascular pathology, and better cognitive functioning. This suggests that PBA<CA indicate preserved brain structure and could be used as marker of BM.
Background
Though cardiometabolic disorders (CMDs; including type 2 diabetes, heart disease, and stroke) have been individually associated with cognitive decline, their combined effect on the ...prodromal phase of dementia is unknown. We aimed to examine the extent to which CMD multimorbidity is associated with cognitive decline and the risk of cognitive impairment–no dementia (CIND) and its progression to dementia.
Method
Within the Swedish National Study on Aging and Care–Kungsholmen, 2934 dementia‐free adults aged ≥60—consisting of a cognitively intact (n=1821) and a CIND (n= 685) cohort—were followed over 12 years. At baseline and each follow‐up (every 3 or 6 years), participants were administered the Mini‐Mental State Examination (MMSE) and a neuropsychological test battery. CIND was defined as having no dementia and performance ≥1.5 SDs below age group‐specific means in at least one cognitive domain (episodic memory, processing speed, executive function, verbal fluency, or visuospatial ability). Dementia was diagnosed according to DSM‐IV criteria. CMDs were ascertained based on clinical examination, medication use, national patient registry data, and laboratory and instrumental tests. CMD multimorbidity was defined as the presence of ≥2 CMDs. Data were analyzed using multi‐adjusted linear mixed models, Cox regression, and Laplace regression, with adjustment for sociodemographic and vascular risk factors.
Result
Of all participants, 813 (27.7%) had one, 221 had two (7.5%), and 23 (0.8%) had three CMDs at baseline. Compared to no CMDs, the presence of one (β= ‐0.22, 95% CI: ‐0.28 to ‐0.15), two (β= ‐0.28, 95% CI: ‐0.40 to ‐0.16), and three (β= ‐0.40, 95% CI: ‐0.77 to ‐0.03) CMDs was related to accelerated MMSE decline in a dose‐dependent fashion (p<0.001). In Cox models, CMD multimorbidity was associated with nearly double the risk of both CIND (hazard ratio HR 1.71, 95% CI 1.22‐2.41) and the progression of CIND to dementia (1.89, 95% CI 1.17‐3.04). Furthermore, CMD multimorbidity anticipated the onset of CIND by 2.5 years and its progression to dementia by 2.2 years.
Conclusion
Cardiometabolic multimorbidity accelerates cognitive decline and increases the risk of CIND and dementia, anticipating the occurrence of both CIND and dementia by more than two years.
INTRODUCTION
Cognitive reserve might mitigate the risk of Alzheimer's dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation.
METHODS
We ...examined cross‐sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD‐related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3‐year follow‐up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol.
RESULTS
Higher CRI scores were associated with better cognition. Adjusting for cortisol measures reduced the beneficial association of CRI on cognition. A higher CRI score was associated with better working memory in individuals with higher (favorable) cortisol AM/PM ratio, but not among individuals with low cortisol AM/PM ratio. No association was found between CRI and AD‐related biomarkers.
DISCUSSION
Physiological stress reduces the neurocognitive benefits of cognitive reserve among memory clinic patients.
Highlights
Physiological stress may reduce the neurocognitive benefits accrued from cognitively stimulating and enriching life experiences (cognitive reserve CR) in memory clinic patients.
Cortisol awakening response modified the relation between CR and P‐tau181, a marker of Alzheimer's disease (AD).
Effective stress management techniques for AD and related dementia prevention are warranted.
Background
Social health (SH) markers, including marital status, contact frequency, network size, and social support, have been linked with increased cognitive capability. However, the underlying ...mechanisms remain poorly understood. We aim to investigate whether depression symptoms and inflammatory biomarkers mediate associations between SH and cognitive outcomes.
Method
We used data from waves 1‐9 of the English Longitudinal Study of Ageing, involving 7,136 participants aged 50 or older at baseline. First, we examined associations between SH (wave 1) and depression and inflammatory biomarkers (C‐reactive protein (CRP) and fibrinogen) (wave 2) using linear regression models. Second, we tested associations between a) SH and b) depression and inflammation with subsequent standardised verbal fluency and memory in wave 3 and change between waves 3‐9, indexed using slopes derived from multilevel models. We adjusted for age, sex, socio‐economic position, cardiovascular disease, basic and instrumental activities of daily living, health behaviours, and baseline depression symptoms and cognition. We will also conduct causal mediation analysis.
Result
All SH markers, except contact frequency, were associated with lower subsequent depression, but not inflammatory biomarkers. Greater contact frequency (e.g. once‐twice a week vs <once per year: β = 0.18 0.01, 0.36) and less negative support (β = 0.02 0.00, 0.03) were associated with higher verbal fluency. Larger network size (>6 people vs none: β = 0.007SD/year 0.001, 0.012), less negative (β = 0.001SD/year 0.001, 0.002) and more positive support (β = 0.001SD/year 0.000, 0.001) were linked with slower memory decline, and more positive support predicted slower verbal fluency decline (β = 0.001SD/year 0.000, 0.001). Depression symptoms were associated with lower memory and verbal fluency, and faster memory decline (β = ‐0.001SD/year ‐0.001, ‐0.000) and verbal fluency (β = ‐0.001SD/year ‐0.001, ‐0.000). CRP was associated with lower verbal fluency (β = ‐0.02 ‐0.04, 0.00), whereas fibrinogen was linked with faster memory decline (β = ‐0.001SD/year ‐0.003, ‐0.000).
Conclusion
Depression symptoms and SH showed associations with subsequent cognitive capability and change. SH was linked with lower depression, but not inflammatory biomarkers. Findings highlight the potential for depression to underpin associations between SH and cognition, a pathway which we will test using causal mediation analysis. We will also examine whether findings replicate in the Swedish National Study of Aging and Care in Kungsholmen.
The Mediterranean Diet Foundation, in collaboration with the International Menarini Foundation, organized the “International Conference on Mediterranean Diet and Health: A Lifelong Approach.” The ...Conference was held in Ostuni (Puglia, Italy) from March 30 to April 1, 2017. The event received the endorsement of the American Federation for Aging Research, the Research Consortium “Luigi Amaducci,” the European Nutrition for Health Alliance, the European Union Geriatric Medicine Society, the Clinical Section of the International Association of Gerontology and Geriatrics—European Region, the National Research Council Research Project on Aging, the Italian Society of Gerontology and Geriatrics, and the Italian Society of Clinical Nutrition and Metabolism.
During the conference, results were presented from major studies on dietary interventions aiming to assess the efficacy of the Mediterranean diet in the prevention of chronic diseases and the potential underlying mechanisms. Twenty-six international speakers, in seven different sessions, discussed the biological basis, clinical impact, health policy, and behavioral implications of the Mediterranean diet, and its use in potential interventions for health promotion.
PDF
