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.

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.

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.

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.

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.

Associations of advanced glycation end-products with cognitive functions in individuals with and without type 2 diabetes: the maastricht study.

CONTEXT: Advanced glycation end-products (AGEs) are thought to be involved in the pathogenesis of Alzheimer's disease. AGEs are products resulting from nonenzymatic chemical reactions between reduced sugars and proteins, which accumulate during natural aging, and their accumulation is accelerated in hyperglycemic conditions such as type 2 diabetes mellitus. OBJECTIVE: The objective of the study was to examine associations between AGEs and cognitive functions. DESIGN, SETTING, AND PARTICIPANTS: This study was performed as part of the Maastricht Study, a population-based cohort study in which, by design, 215 participants (28.1%) had type 2 diabetes mellitus. MAIN OUTCOME MEASURES: We examined associations of skin autofluorescence (SAF) (n = 764), an overall estimate of skin AGEs, and specific plasma protein-bound AGEs (n = 781) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition. RESULTS: After adjustment for demographics, diabetes, smoking, alcohol, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, and lipid-lowering medication use, higher SAF was significantly associated with worse delayed word recall (regression coefficient, b = -0.44; P = .04), and response inhibition (b = 0.03; P = .04). After further adjustment for systolic blood pressure, cardiovascular disease, estimated glomerular filtration rate, and depression, associations were attenuated (delayed word recall, b = -0.38, P = .07; response inhibition, b = 0.02, P = .07). Higher pentosidine levels were associated with worse global cognitive functioning (b = -0.61; P = .04) after full adjustment, but other plasma AGEs were not. Associations did not differ between individuals with and without diabetes. CONCLUSION: We found inverse associations of SAF (a noninvasive marker for tissue AGEs) with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression.

Co-Presence of Multimorbidity and Disability with Frailty: An Examination of Heterogeneity in the Frail Older Population.

BACKGROUND: Frailty is often associated with multimorbidity and disability. OBJECTIVES: We investigated heterogeneity in the frail older population by characterizing five subpopulations according to quantitative biological markers, multimorbidity and disability, and examined their association with mortality and nursing home admission. DESIGN: Observational study. PARTICIPANTS: Participants (n=4,414) were from the population-based Age Gene/Environment Susceptibility Reykjavik Study. MEASUREMENTS: Frailty was defined by ≥ 3 of five characteristics: weight loss, weakness, reduced energy levels, slowness and physical inactivity. Multimorbidity was assessed using a simple disease count, based on 13 prevalent conditions. Disability was assessed by five activities of daily living; participants who had difficulty with one or more tasks were considered disabled. Differences among frail subpopulations were based on the co-presence of multimorbidity and disability. Differences among the following subpopulations were examined: 1) Non-frail (reference group); 2) Frail only; 3) Frail with disability; 4) Frailty with multimorbidity; 5) Frail with disability and multimorbidity. RESULTS: Frailty was present in 10.7% (n=473). Frailty was associated with increased risk for mortality (OR 1.40; 95% CI 1.15-1.69) and nursing home admission (OR 1.50; 95% CI 1.16-1.93); risks differed by subpopulations. Compared to the non-frail, the frail only group had poorer cognition and increased inflammation levels but did not have increased risk for mortality (OR 1.40; 95% CI 0.84-2.33) or nursing home admission (OR 1.01; 95% CI 0.46-2.21). Compared to the non-frail, the other frail subpopulations had significantly poorer cognition, increased inflammation levels, more white matter lesions, higher levels of calcium, glucose and red cell distribution width and increased risk for mortality and nursing home admission. CONCLUSIONS: The adverse health risks associated with frailty in the general older adult population may primarily be driven by increased disease burden and disability.

[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.

Use of an electronic cognitive aid by a person with Korsakoff syndrome.

OBJECTIVE: The purpose of the current study was to evaluate the feasibility and the effectiveness of the use of a customized personal digital assistant (PDA) to support cognitive functioning in a person with Korsakoff syndrome. METHOD: The PDA was compared with no external support and the use of a memory watch in a single case experimental design. Three main personal goal tasks were defined: "arrive at appointments on time", "execute a long-term task successfully", and "remember to ask for medication". RESULTS: No significant differences were found between the use of the memory watch and the use of the customized PDA. PDA use was perceived as feasible and effective and was considered as a more comprehensive aid than the memory watch. CONCLUSION: This study shows that a person with Korsakoff syndrome is able to use and benefit from a customized PDA. Replication of these findings in a larger effectiveness study is necessary.

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.

[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.

Functional integration of parietal lobe activity in early Alzheimer disease.

OBJECTIVES: Parietal lobe dysfunction is an important characteristic of early Alzheimer disease (AD). Functional studies have shown conflicting parietal activation patterns indicative of either compensatory or dysfunctional mechanisms. This study aimed at examining activation differences in early AD using a visuospatial task. We focused on functional characteristics of the parietal lobe and examined compensation or disconnection mechanisms by combining a fMRI task with effective connectivity measures from Granger causality mapping (GCM). METHODS: Eighteen male patients with amnestic mild cognitive impairment (aMCI) and 18 male cognitively healthy older individuals were given a mental rotation task with different rotation angles. RESULTS: There were no behavioral group differences on the fMRI task. Separate measurements at each angle revealed widespread activation group differences. More temporal and parietal activation in the higher angle condition was observed in patients with aMCI. The parametric modulation, which identifies regions associated with increasing angle, confirmed these results. The GCM showed increased connectivity within the parietal lobe and between parietal and temporal regions in patients with aMCI. Decreased connectivity was found between the inferior parietal lobule and posterior cingulate gyrus. Connectivity patterns correlated with memory performance scores in patients with aMCI. CONCLUSIONS: Our results demonstrate increased effective temporoparietal connectivity in patients with aMCI, while maintaining intact behavioral performance. This might be a compensational mechanism to counteract a parietal-posterior cingulate gyrus disconnection. These findings highlight the importance of connectivity changes in the pathophysiology of AD. In addition, effective connectivity may be a promising method for evaluating interventions aimed at the promotion of compensatory mechanisms.

MTHFR polymorphisms and cognitive ageing in the ninth decade: the Lothian Birth Cohort 1921.

Low blood levels of B vitamins have been implicated in age-associated cognitive impairment. The present study investigated the association between genetic variation in folate metabolism and age-related cognitive decline in the ninth decade of life. Both the 677C>T (rs1801133) polymorphism and the scarcely studied 1298A>C (rs1801131) polymorphism of the MTHFR gene were assessed in relation to cognitive change over 8 years in older community-dwelling individuals. MTHFR genotype was determined in 476 participants of the Lothian Birth Cohort 1921, whose intelligence was measured in childhood in the Scottish Mental Survey of 1932. Cognitive performance on the domains of verbal memory, reasoning and verbal fluency was assessed at mean age of 79 (n = 476) and again at mean ages of 83 (n = 275) and 87 (n = 180). Using linear mixed models, the MTHFR 677C>T and 1298A>C variants were not associated with the rate of cognitive change between 79 and 87 years, neither in the total sample, nor in a subsample of individuals with erythrocyte folate levels below the median. APOE E4 allele carrier status did not interact with MTHFR genotype in affecting change in cognitive performance over 8 years. No significant combined effect of the two polymorphisms was found. In conclusion, MTHFR 677C>T and 1298A>C polymorphisms were not associated with individual change in cognitive functioning in the ninth decade of life. Although polymorphisms in the MTHFR gene may cause disturbances in folate metabolism, they do not appear to be accompanied by changes in cognitive functioning in old age.

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.

Recurrent pain is associated with decreased selective attention in a population-based sample.

Studies which have examined the impact of pain on cognitive functioning in the general population are scarce. In the present study we assessed the predictive value of recurrent pain on cognitive functioning in a population-based study (N=1400). Furthermore, we investigated the effect of pain on cognitive functioning in individuals with specific pain complaints (i.e. back pain, gastric pain, muscle pain and headache). Cognitive functioning was assessed using the Stroop Color-Word Interference test (Stroop interference), the Letter-Digit-Substitution test (LDST) and the Visual Verbal learning Task (VVLT). Pain was measured with the COOP/WONCA pain scale (Dartmouth Primary Care Cooperative Information Project/World Organization of National Colleges, Academies, and Academic Associations of General Practice /Family Physicians). We controlled for the effects of age, sex, level of education and depressive symptoms. It was demonstrated that pain had a negative impact on the performance on the Stroop interference but not on the VVLT and the LDST. This indicates that subjects who reported extreme pain had more problems with selective attention and were more easily distracted. Effects were in general larger in the specific pain groups when compared to the associations found in the total group. Implications of these findings are discussed. The experience of recurrent pain has a negative influence on selective attention in a healthy population.

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.

The posterior parahippocampal gyrus is preferentially affected in age-related memory decline.

Atrophy in the medial temporal lobe is generally considered to be highly associated with age-related memory decline. Volume loss in the hippocampus and entorhinal cortex has extensively been investigated, but the posterior parts of the parahippocampal gyrus have received little attention. The present MRI study investigated whether volume differences in medial temporal lobe areas are differentially related to age-related memory decline. Thirty-nine subjects from a longitudinal study on cognitive aging (the Maastricht Aging Study) have been examined: 20 participants (mean age=67 years, range 52-80) with memory decline over a period of 12 years were matched to 19 participants without memory decline. Manual tracing was performed on 3T MR images to measure the volumes of the anterior, middle and posterior parts of the hippocampus and parahippocampal gyrus. A robust group difference and a significant association with memory decline were observed only in the posterior part of the parahippocampal gyrus. Our results may suggest that the posterior parahippocampal gyrus plays a key role in age-related memory decline.

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.

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.