To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons.
This is a ...cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions.
People with multiple (≥ 2) CMBs had lower Z scores on tests of processing speed (β-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62).
Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community.
To examine the associations of fatty acid and fish intake with cognitive function.
Data are from a cross-sectional population-based study among 1,613 subjects ranging from 45 to 70 years old. From ...1995 until 2000, an extensive cognitive battery was administered and compound scores were constructed for memory, psychomotor speed, cognitive flexibility (i.e., higher order information processing), and overall cognition. A self-administered food-frequency questionnaire was used to assess habitual food consumption. The risk of impaired cognitive function (lowest 10% of the compound score) according to the energy adjusted intake of fatty acids was assessed with logistic regression, adjusting for age, sex, education, smoking, alcohol consumption, and energy intake.
Marine omega-3 polyunsaturated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid) were inversely related to the risk of impaired overall cognitive function and speed (per SD increase: OR = 0.81, 95% CI 0.66 to 1.00 and OR = 0.72, 95% CI 0.57 to 0.90). Results for fatty fish consumption were similarly inverse. Higher dietary cholesterol intake was significantly associated with an increased risk of impaired memory and flexibility (per SD increase: OR = 1.27, 95% CI 1.02 to 1.57 and OR = 1.26, 95% CI 1.01 to 1.57). Per SD increase in saturated fat intake, the risk of impaired memory, speed, and flexibility was also increased, although not significantly.
Fatty fish and marine omega-3 PUFA consumption was associated with a reduced risk and intake of cholesterol and saturated fat with an increased risk of impaired cognitive function in this middle-aged population.
Based on many experimental and observational studies we now understand that neurodegenerative brain changes begin by middle age. Characteristics of the risk factors for these brain changes may also ...change with age. A review is conducted of studies that report on the association of mid-life risk factors to late cognitive impairment and dementia. Issues related to the interpretation of the data are discussed. The studies suggest that mid-life cardiovascular risk factors, and in particular elevated levels of blood pressure, increase the risk for late-life cognitive impairment and dementia. Our understanding the contribution of cardiovascular risk factors to late age brain disease has been helped tremendously by prospective studies with long follow-up. To better understand which risk factors lead to disease initiation, progression and prognosis, a life course approach to the epidemiologic study of dementia is needed.
Background Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent ...studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear. Methods Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed. Results Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio HR: 1.14; 95% confidence interval CI: 1.11–1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12–1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07–1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07–1.18). Furthermore, the RDW–mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21–1.44). Conclusions RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.
Previous studies have suggested that migraine is a risk factor for brain lesions, but methodological issues hampered drawing definite conclusions. Therefore, we initiated the magnetic resonance ...imaging (MRI) ‘CAMERA’ (Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis) study. We summarize our previously published results. A total of 295 migraineurs and 140 controls were randomly selected from a previously diagnosed population-based sample (n = 6039), who underwent an interview, physical examination and a brain MRI scan. Migraineurs, notably those with aura, had higher prevalence of subclinical infarcts in the posterior circulation odds ratio (OR) 13.7; 95% confidence interval (CI) 1.7, 112. Female migraineurs were at independent increased risk of white matter lesions (WMLs; OR 2.1; 95% CI 1.0, 4.1), and migraineurs had a higher prevalence of brainstem hyperintense lesions (4.4% vs. 0.7%, P = 0.04). We observed a higher lifetime prevalence of (frequent) syncope and orthostatic insufficiency in migraineurs; future research needs to clarify whether autonomic nervous system dysfunction could explain (part of) the increased risk of WMLs in female migraineurs. Finally, in migraineurs aged < 50 years, compared with controls, we found evidence of increased iron concentrations in putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Higher risks in those with higher attack frequency or longer disease duration were found consistent with a causal relationship between migraine and lesions. This summary of our population-based data illustrates that migraine is associated with a significantly increased risk of brain lesions. Longitudinal studies are needed to assess whether these lesions are progressive and have relevant (long-term) functional correlates.
We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total ...n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.
A small magnetic resonance imaging (MRI) study showed increased iron depositions in the periaqueductal grey matter in migraineurs, suggestive of a disturbed central antinociceptive neuronal network. ...With 1.5–T MRI, we assessed iron concentrations in seven deep brain nuclei in a large population-based cohort. We compared T2 values between migraineurs (n = 138) and controls (n = 75), with multivariate regression analysis. Analyses were conducted in age strata (< 50, n = 112; ≥ 50) because iron measures are increasingly influenced by non-iron-related factors in the older group. Overall, migraineurs and controls did not differ, nor did migraineurs with vs. without aura. In the younger migraineurs compared with controls, T2 values were lower in the putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Similarly, in these younger migraineurs, controlling for age, those with longer migraine history had lower T2 values in the putamen (P = 0.01), caudate (P = 0.04) and red nucleus (P = 0.001). Repeated migraine attacks are associated with increased iron concentration/accumulation in multiple deep nuclei that are involved in central pain processing and migraine pathophysiology. It remains unclear whether iron accumulation in the antinociceptive network has a causative role in the development of (chronic) migraine headache.
Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for ...cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs.
Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death.
Compared to controls, migraineurs were more likely to smoke (OR = 1.43 1.1 to 1.8), less likely to consume alcohol (OR = 0.58 0.5 to 0.7), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL OR = 1.43 (0.97 to 2.1), TC:HDL ratio > 5.0 OR = 1.64 (1.1 to 2.4)), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg OR = 1.76 (1.04 to 3.0)), and report a history of early onset CHD or stroke (OR = 3.96 1.1 to 14.3); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 1.05 to 4.0). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura.
Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.
A frailty index (FI) based on the accumulation of deficits typically has a submaximal limit at about 0.70. The objectives of this study were to examine how population characteristics of the FI change ...in the Honolulu-Asia Aging Study cohort, which has been followed to near-complete mortality. In particular, we were interested to see if the limit was exceeded.
Secondary analysis of six waves of the Honolulu-Asia Aging Study. Men (n = 3,801) aged 71-93 years at baseline (1991) were followed until death (N = 3,455; 90.9%) or July 2012. FIs were calculated across six waves and the distribution at each wave was evaluated. Kaplan-Meier analyses and Cox proportional hazard models were performed to examine the relationship of frailty with mortality.
At each wave, frailty was nonlinearly associated with age, with acceleration in later years. The distributions of the FIs were skewed with long right tails. Despite the increasing mortality in each successive wave, the 99% submaximal limit never exceeded 0.65. The risk of death increased with increasing values of the FI (eg, the hazard rate increased by 1.44 95% CI = 1.39-1.49 with each increment in the baseline FI grouping). Depending on the wave, the median survival of people with FI more than 0.5 ranged 0.84-2.04 years.
Even in a study population followed to almost complete mortality, the limit to deficit accumulation did not exceed 0.65, confirming a quantifiable, maximum number of health deficits that older men can tolerate.
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