Lower verbal intelligence is associated with diabetic complications and slower walking speed in people with Type 2 diabetes: the Maastricht Study.

AIMS: To determine the association of verbal intelligence, a core constituent of health literacy, with diabetic complications and walking speed in people with Type 2 diabetes. METHODS: This study was performed in 228 people with Type 2 diabetes participating in the Maastricht Study, a population-based cohort study. We examined the cross-sectional associations of score on the vocabulary test of the Groningen Intelligence Test with: 1) determinants of diabetic complications (HbA1c , blood pressure and lipid level); 2) diabetic complications: chronic kidney disease, neuropathic pain, self-reported history of cardiovascular disease and carotid intima-media thickness; and 3) walking speed. Analyses were performed using linear regression and adjusted in separate models for potential confounders and mediators. Significant age- and sex-adjusted associations were additionally adjusted for educational level in a separate model. RESULTS: After full adjustment, lower verbal intelligence was associated with the presence of neuropathic pain [odds ratio (OR) 1.18, 95% CI 1.02;1.36], cardiovascular disease (OR 1.14, 95% CI 1.01;1.30), and slower walking speed (regression coefficient -0.011 m/s, 95% CI -0.021; -0.002 m/s). These associations were largely explained by education. Verbal intelligence was not associated with blood pressure, glycaemic control, lipid control, chronic kidney disease or carotid intima-media thickness. CONCLUSIONS: Lower verbal intelligence was associated with the presence of some diabetic complications and with a slower walking speed, a measure of physical functioning. Educational level largely explained these associations. This implies that clinicians should be aware of the educational level of people with diabetes and should provide information at a level of complexity tailored to the patient.

[Mindfulness, cognitive function and 'successful ageing']. / Mindfulness, cognitieve functies en 'succesvol ouder worden'

There is ample empirical evidence that cultivation of mindfulness in dedicated target populations has positive health effects, specifically in the context of stress management and mental disorders. Research into the effectiveness of mindfulness-based interventions (MBI) in age-related conditions and disorders is still in its infancy. This paper describes, in brief, the scientific background of MBI and its potential to contribute to successful ageing and the care for and wellbeing of older people. Special focus is dedicated to the contribution of optimal cognitive abilities to this success and to what extent MBI may support cognitive reserve.

Effectiveness of an electronic cognitive aid in patients with acquired brain injury: a multicentre randomised parallel-group study.

The objective of the study was to examine the effectiveness of a customised personal digital assistant (PDA) as a cognitive aid for people with acquired brain injury, using a randomised parallel-group study. The participants were 34 patients with acquired brain injury in a cognitive rehabilitation setting. The experimental group used a customised PDA, while the control group received care-as-usual (paper-and-pencil aids). Measurements were conducted at baseline (T0), after 8 hours of training (T1), after 16 hours of training (T2), and at 5-month follow-up (T3). The main outcome was the attainment of individualised goals. Both groups showed a significant increase in goal attainment (GAS) (p < .001). There were no significant differences between the groups at T1 or T2 on any of the other outcome measures. It was concluded that the customised PDA was as effective as paper-and-pencil aids, and may therefore serve as a useful alternative when choosing the optimal rehabilitation strategy for a patient.

Cognitive Functioning in Survivors of Hematopoietic Stem Cell Transplantation Compared With a Matched General Population Sample-The Maastricht Observational Study of Late Effects After Stem Cell trAnsplantation Study.

Although cognitive problems can recover over time, a subgroup of hematopoietic stem cell transplantation (HCT) survivors experience persistent cognitive problems in the long term. Despite these implications, studies assessing cognitive functioning in HCT survivors are limited. The aim of the present study was (1) to quantify the prevalence of cognitive impairment in patients treated with HCT who survived at least 2 years and to compare these with a matched reference group representing the general population; (2) to identify potential determinants of cognitive functioning within the HCT survivor group. Within the single-center Maastricht Observational study of late effects after Stem cell trAnsplantation, cognitive performance was assessed by a neuropsychological test battery divided into 3 cognitive domains: memory, information processing speed, and executive function and attention. An overall cognition score was calculated as the average of the domain scores. A total of 115 HCT survivors were group-matched on a 1:4 ratio to the reference group by age, sex, and level of education. Regression analyses adjusted for different sets of covariates including demographic and health- and lifestyle-related factors were used to test for differences in cognition between HCT survivors and the reference group resembling the general population. A limited set of clinical characteristics (diagnosis, type of transplant, time since treatment, conditioning regimen with total body irradiation and age at time of transplantation) were assessed as potential determinants of neurocognitive dysfunction among HCT survivors. Cognitive impairment was defined as scores in the cognitive domains < -1.5 standard deviation (SD) from what can be expected based on someone's age, sex, and education. The mean age at time of transplantation was 50.2 (SD ± 11.2) years, and the mean number of years after transplant was 8.7 (SD ± 5.7) years. The majority of HCT survivors were treated with autologous HCT (n = 73 [64%]). The prevalence of cognitive dysfunction was 34.8% in HCT survivors and 21.3% in the reference group (p = .002.) When adjusted for age, sex, and level of education, HCT survivors had a worse overall cognition score (b = -0.35; 95% confidence interval [CI], -0.55 to -0.16; p < .001), translating into 9.0 years of higher cognitive age. Analyses of specific cognitive domain scores showed that HCT survivors scored worse on memory (b = -0.43; 95% CI, -0.73 to -0.13; p = .005), information processing speed (b = -0.33; 95% CI, -0.55 to -0.11; p = .003), and executive function and attention (b = -0.29; 95% CI, -.55 to -.03; p = .031) than the reference group. The odds of cognitive impairment were on average 2.4 times higher among HCT survivors than the reference group (odd ratio = 2.44; 95% CI, 1.47-4.07; p = .001). Within the HCT survivor group none of the tested clinical determinants of cognitive impairment were significantly associated with cognition. This cohort study showed evidence for worse cognitive functioning in HCT survivors encompassing all three cognitive domains, respectively memory, information processing speed, and executive and attention compared to a reference group that represents the general population translating into nine years of faster cognitive ageing in HCT survivors than can be expected based on their chronological age. It is important to increase awareness for signs of neurocognitive dysfunction after HCT in clinicians and HCT survivors.

[The shrinking brain: result of normal aging or of selection bias in research?]. / Het krimpende brein: normale veroudering of een gevolg van selectiebias in het onderzoek?

The volume of our brain decreases as we age. This has been demonstrated by several large studies on normal aging. A recent study indicates, however, that the extent of this decline in normal aging probably has been overestimated because these studies have included subjects with preclinical disorders. In this article, an example from science is used to describe what effect selection bias may have on our model of the aging brain.

Age differences in speed of processing are partially mediated by differences in axonal integrity.

Advanced age is associated with declines in brain structure and in cognitive performance, but it is unclear which aspects of brain aging mediate cognitive declines. We inquired if individual differences in white matter integrity contribute to age differences in two cognitive domains with established vulnerability to aging: executive functioning and speed of processing. The participants were healthy volunteers aged 50-81, some of whom had elevated blood pressure, a known vascular risk factor. Using latent variable analyses, we examined whether age differences in regional white matter integrity mediated age-related differences in executive functions and speed of processing. Although diffusion-related latent variables showed stronger age differences than white matter volumes and white matter hyperintensity volumes, only one of them was significantly associated with cognitive performance. Smaller linear anisotropy partially mediated age-related reduction in speed of processing. The effect was significant in posterior (temporal-parietal-occipital) but not anterior (frontal) region, and appeared stronger for cognitive rather than reaction time measures of processing speed. The presence of hypertensive participants did not affect the results. We conclude that in healthy adults, deterioration of axonal integrity and ensuing breech of connectivity may underpin age-related slowing of information processing.

Brain-specific fatty acid-binding protein is elevated in serum of patients with dementia-related diseases.

BACKGROUND: There is a need for biomarkers in accessible matrices, such as blood, for the diagnosis of neurodegenerative diseases. The aim of this study was to measure the serum levels of brain-type fatty acid-binding protein (FABP) and heart-type FABP in patients with dementia-involving diseases. METHODS: Brain- and heart-type FABP were measured in serum samples from patients with either Alzheimer's disease (AD) (n = 31), Parkinson's disease (PD, n = 43), or other cognitive disorders (OCD, n = 42) and in 52 healthy controls. The localization of brain- and heart-type FABP was determined in brain sections by immunohistochemistry. RESULTS: Brain-type FABP levels were elevated in serum of 29%, 35%, and 24% of the patients with AD, PD, and OCD, respectively, and in 2% of the healthy donors. Heart-type FABP serum levels were not different amongst the patient groups. Brain-type and heart-type FABP expression was observed in reactive astrocytes in brain sections of patients with AD. CONCLUSIONS: In contrast to heart-type FABP, serum levels of brain-type FABP are elevated in a significant proportion of patients with various neurodegenerative diseases and can therefore have importance for defining subgroups of these patients.

Influence of multimorbidity on cognition in a normal aging population: a 12-year follow-up in the Maastricht Aging Study.

OBJECTIVE: The prevalence of multimorbidity has risen considerably because of the increase in longevity and the rapidly growing number of older individuals. Today, only little is known about the influence of multimorbidity on cognition in a normal healthy aging population. The primary aim of the present study was to investigate the effect of multimorbidity on cognition over a 12-year period in an adult population with a large age range. METHODS: Data were collected as part of the Maastricht Aging Study (MAAS), a prospective study into the determinants of cognitive aging. Eligible MAAS participants (N = 1763), 24-81 years older, were recruited from the Registration Network Family Practices (RNH) which enabled the use of medical records. The association between 96 chronic diseases, grouped into 23 disease clusters, and cognition on baseline, at 6 and 12 years of follow-up, were analyzed. Cognitive performance was measured in two main domains: verbal memory and psychomotor speed. A multilevel statistical analysis, a method that respects the hierarchical data structure, was used. RESULTS: Multiple disease clusters were associated with cognition during a 12-year follow-up period in a healthy adult population. The disease combination malignancies and movement disorders multimorbidity also appeared to significantly affect cognition. CONCLUSIONS: The current results indicate that a variety of medical conditions adversely affects cognition. However, these effects appear to be small in a normal healthy aging population.

Multimorbidity and its relation to subjective memory complaints in a large general population of older adults.

BACKGROUND: Multimorbidity has been suggested to be associated with a variety of negative health-related outcomes. The present study was designed to evaluate the association between multimorbidity and subjective memory complaints. METHODS: This cross-sectional study was based on data obtained from a postal survey designed by the Public Health Service (Gemeentelijke Gezondheids Dienst, GGD) involving 15,188 persons aged 55 years and over living independently in Limburg, the Netherlands. Multivariate logistic regression analyses, adjusted for potentially important covariates, were performed to evaluate the association between self-reported multimorbidity and three outcomes related to subjective memory complaints. RESULTS: Multimorbidity was indeed related to subjective memory complaints. The association between multimorbidity and subjective memory complaints was positively influenced by age. Moreover, multimorbidity was related to the degree of worrying about memory complaints in people who perceived themselves as forgetful. Multimorbidity was also associated with reporting a larger increase in these subjective memory complaints during the past year. In this latter case, multimorbidity had more prognostic capability in men than in women. Psychological distress was related to all three subjective memory-related outcome measures. CONCLUSIONS: In our sample, which was representative of the Dutch population, multimorbidity was associated with subjective memory complaints. The relationship between multimorbidity and subjective memory complaints differed between men and women and between age groups.

Multiple indicators of age-related differences in cerebral white matter and the modifying effects of hypertension.

We investigated differences associated with age and hypertension, a common risk factor for vascular disease, in three aspects of white matter integrity--gross regional volumes of the white matter, volume of the white matter hyperintensities (WMH) and diffusion properties. We acquired MRI scans on 93 adult volunteers (age 50-77 years; 36 with diagnosis of hypertension or elevated blood pressure), and obtained all measures in seven brain regions: frontal, temporal, parietal and occipital white matter, and the genu, body and splenium of the corpus callosum. The results demonstrated robust age-related differences in diffusion-based indices of cerebral white matter integrity and age-related increase in the WMH volume, but no age differences in the gross regional volumes of the white matter. Hypertension was associated with decline in fractional anisotropy, and exacerbated age differences in fractional anisotropy more than those in the volume of WMH. These findings indicate that of all examined measures, diffusion-based indices of white matter integrity may be the most sensitive indicators of global and regional declines and vascular damage in the aging brain.

The effect of the APOE-epsilon4 allele and ACE-I/D polymorphism on cognition during a two-year follow-up in first-ever stroke patients.

BACKGROUND: Cognitive impairment is commonly observed after stroke and has a negative impact on survival and rehabilitation. Some stroke patients deteriorate in cognitive functioning whereas others do not. Environmental and demographic risk factors cannot fully explain this. There is growing evidence that a genetic predisposition plays a role in the pathogenesis of post-stroke cognitive decline. OBJECTIVE: To study the influence of the APOE-epsilon4 allele and the ACE-I/D polymorphism on cognitive functioning after stroke. METHODS: We included 194 first-ever stroke patients of whom information about APOE genotyping and ACE-I/D polymorphism was available in 92 and 129 patients, respectively. Patients were cognitively assessed at 1, 6, 12 and 24 months after the event. Linear mixed models with slope estimates were used to study the influence of the APOE-epsilon4 allele and the ACE-I/D polymorphism on the MMSE score, CAMCOG, executive functioning, psychomotor speed, and verbal memory function during follow-up. RESULTS: Patients carrying the APOE-epsilon4 allele more often suffered a lacunar infarction than non-carriers. The APOE-epsilon4 allele had no effect on cognitive functioning during the follow-up. ACE-DD homozygosity was associated with a worse performance in executive functioning compared to patients with neither an APOE-epsilon4 allele nor the ACE-DD genotype. There was no interaction between the APOE-epsilon4 allele and the ACE-DD phenotype in the prediction of cognitive decline. CONCLUSION: The ACE-DD genotype may be associated with post-stroke cognitive decline while the APOE-epsilon4 allele is not. Further research is needed to examine the role of genetic risk factors for post-stroke cognitive decline and to determine why some patients deteriorate cognitively after stroke but others do not.

Predictive value of mild cognitive impairment for dementia. The influence of case definition and age.

BACKGROUND/AIMS: In population studies, different mild cognitive impairment (MCI) definitions have been used to predict dementia at a later stage. This study compared predictive values of different MCI definitions for dementia, and the effect of age on the predictive values was investigated. METHODS: This study was conducted as part of an ongoing longitudinal study into the determinants of cognitive aging, the Maastricht Aging Study. RESULTS: MCI best predicted dementia when multiple cognitive domains were considered and subjective complaints were not (sensitivity: 0.66, specificity: 0.78). Age had a strong influence on the sensitivity of MCI for dementia (age 60-70 years: sensitivity = 0.56; age 70-85 years: sensitivity = 0.70). CONCLUSION: The inclusion of multiple cognitive domains and participants aged 70 years and older leads to the best prediction of dementia, regardless of subjective complaints.

Diabetes mellitus type II as a risk factor for depression: a lower than expected risk in a general practice setting.

The aim of the present study was to determine whether a diagnosis of diabetes mellitus (DM) in a primary setting is associated with an increased risk of subsequent depression. A retrospective cohort design was used based on the Registration Network Family Practice (RNH) database. Patients diagnosed with diabetes mellitus at or after the age of 40 and who were diagnosed between 01-01-1980 and 01-01-2007 (N = 6,140), were compared with age-matched controls from a reference group (N = 18,416) without a history of diabetes. Both groups were followed for an emerging first diagnosis of depression (and/or depressive feelings) until January 1, 2008. 2.0% of the people diagnosed with diabetes mellitus developed a depressive disorder, compared to 1.6% of the reference group. After statistical correction for confounding factors diabetes mellitus was associated with an increased risk of developing subsequent depression (HR 1.26; 95% CI: 1.12-1.42) and/or depressive feelings (HR 1.33; 95% CI: 1.18-1.46). After statistical adjustment practice identification code, age and depression preceding diabetes, were significantly related to a diagnosis of depression. Patients with diabetes mellitus are more likely to develop subsequent depression than persons without a history of diabetes. Results from this large longitudinal study based on a general practice population indicate that this association is weaker than previously found in cross-sectional research using self-report surveys. Several explanations for this dissimilarity are discussed

Measuring rebelliousness and predicting health behaviour and outcomes: an investigation of the construct validity of the Social Reactivity Scale.

The Social Reactivity Scale is a questionnaire measure of individual differences in rebelliousness. The associations between rebelliousness, health behaviours and health outcomes were examined in two Dutch samples by means of cross-sectional survey data. We found moderate support for the reliability and construct validity of the scale. Findings were suggestive of rebelliousness, first, being associated with low control beliefs, second, being related to hostility and, third, also heightening the risk of engaging in unhealthy behaviours and that of poor health (perhaps through deliberately rejecting health education messages). Findings thus contribute to the ongoing emergence of an empirically viable theoretical construct.

Interaction between blood-brain barrier and glymphatic system in solute clearance.

Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-ß, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-ß accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease.

Cognitive functioning in healthy older adults aged 64-81: a cohort study into the effects of age, sex, and education.

The objective of this study was to determine a possible differential effect of age, education, and sex on cognitive speed, verbal memory, executive functioning, and verbal fluency in healthy older adults. A group of 578 healthy participants in the age range of 64-81 was recruited from a large population study of healthy adults (Maastricht Aging Study). Even in healthy individuals in this restricted age range, there is a clear, age-related decrease in performance on executive functioning, verbal fluency, verbal memory, and cognitive speed tasks. The capacity to inhibit information is affected most. Education had a substantial effect on cognitive functioning: participants with a middle or high level of education performed better on cognitive tests than did participants with a low level of education. Women performed better than men on verbal memory tasks. Therefore, education and sex must be taken into account when examining an older individual's cognitive performance.

Obesity and Cognitive Decline in Adults: Effect of Methodological Choices and Confounding by Age in a Longitudinal Study.

BACKGROUND AND OBJECTIVES: Obesity has been associated with increased risk of cognitive impairment or dementia, but recent findings are contradictory, possibly due to methodological differences. The present study tries to clarify these inconsistencies by following the cognitive trajectories of individuals with obesity over 12 years and studying the effect of obesity status (obesity at baseline versus incident obesity at follow-up), chronicity, definition, potential confounding (e.g. age, cardiovascular factors), and non-linear associations. DESIGN: Longitudinal study with 12 years follow-up. SETTING: Community based. PARTICIPANTS: 1,807 cognitively healthy individuals (aged 24-83) from the Maastricht Aging Study (1992-2004). MEASUREMENTS: Memory, executive function and processing speed were assessed at baseline and at 6- and 12-year follow-up. Obesity was defined as having a body mass index (BMI) of ≥ 30.0 kg/m2 or waist circumference (WC) of > 102 cm for men and > 88 cm for women. RESULTS: At baseline, 545 persons were obese (BMI: 329 (18%); WC: 494 (27%); both: 278 (15%). They showed faster decline in memory, executive function, and processing speed. Chronic obese showed less widespread impairment than those who regained normal weight. Associations across cognitive domains were weaker for obesity defined by BMI than for WC. At follow-up, 190 developed obesity, and they performed worse on executive function at baseline, but showed less decline compared with participants with normal weight. Yet, age-stratification and post-hoc analyses showed that most of these associations were confounded by age. CONCLUSIONS: This study shows that the association between obesity and cognitive decline was confounded by the effect of age on rate of decline. Future studies should take this into account.

Prevalence of primitive reflexes and the relationship with cognitive change in healthy adults: a report from the Maastricht Aging Study.

OBJECTIVES: Primitive reflexes (PR) generally disappear early in life but may reappear later, in which case they are often associated with chronic neurological conditions, such as dementia or Parkinson's disease. Studies have shown that the presence of PRs may be indicative of both the severity and rate of progression of these diseases and may be the result of disinhibition of cortical networks. The association between PRs and cognitive function in usual ageing is unclear. We investigated whether the occurrence, amplitude, and persistence of four nociceptive (glabbelar tap, palmomental, pollicomental, and snout reflexes), three prehensile reflexes (suck, palmar grasp, and rooting), and two other reflexes (mouth open finger-spread and nuchocephalic reflexes) were related to performance in specific cognitive domains in normal ageing individuals. METHODS: Four-hundred and seventy normal aging participants (25-82 years) in the Maastricht Aging Study (MAAS), were included in the study. They were neurologically and cognitively screened at baseline and were retested after 3 (only individuals aged 50 years and older at baseline) and 6 years. RESULTS: The prevalence of most PRs increased with age: 47% of men aged 25-45 years had at least one PR, compared with 73% of men aged 65-85 year (p = 0.002). In women these percentages were 51 and 75, respectively (p=0.008). The prevalence, amplitude, and persistence of PRs were unrelated to cognition at baseline or at the 3- or 6-year follow-up. CONCLUSIONS: The prevalence of particularly nociceptive reflexes rises substantially with increasing age in normal individuals. However, the presence of PRs cannot be considered to be a marker of cognitive decline in normal aging individuals.

Ambulatory blood pressure, asymptomatic cerebrovascular damage and cognitive function in essential hypertension.

Prolonged exposure to elevated blood pressure (BP) can lead to both structural (white matter lesions (WML) or infarctions) and functional changes in the brain. We studied in previously diagnosed essential hypertensive individuals if diurnal BP variation and ambulatory BP (ABP) profile (daytime, night time and 24-h BP averages) were related to evidence of WML, the presence of 'silent' infarcts, and cognitive performance. A group of 86 patients (mean age 57.4+/-10 years, range 40-80) were first screened for hypertension-related organ damage and underwent 24-h ABP monitoring, magnetic resonance imaging (MRI) of the brain, and a comprehensive neurocognitive assessment. Age and ABP profile were related to more periventricular, but not subcortical, WML and to presence of lacunar infarctions on MRI. After correction for demographical group differences, no association was found between night time dipping of BP on the one hand and both WML load and cognitive parameters (verbal memory, sensorimotor speed, cognitive flexibility) on the other. The presence of lacunar infarctions, however, predicted lower performance on verbal memory. Furthermore, daytime and 24-h pulse pressure averages were associated with pWML, whereas systolic BP and mean arterial pressure (MAP) for daytime, night-time and 24-h periods were higher in patients with lacunar infarctions. Notwithstanding the large variability of WML in this sample, the evidence of a connection between diurnal BP variation and early target organ damage in the brain was not convincing. However, the ABP profile may be predictive of cerebral lesion type.

Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements.

Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.