Thomas Duning

Physical activity and memory functions: An interventional study

Previous studies have suggested beneficial effects of physical activity on cognition. Here, we asked in an interventional approach if physical activity performed at different intensity levels would differentially affect episodic memory function. Additionally, we tried to identify mechanisms mediating these changes. Sixty-two healthy elderly individuals were assessed for level of physical activity, aerobic fitness, episodic memory score, neurotrophin and catecholamine levels, and received a magnetic resonance image of the brain at baseline and after a six months intervention of medium or low-intensity physical activity or control. Increase in total physical activity was positively associated with increase in memory score over the entire cohort, without significant differences between intensity groups. It was also positively associated with increases in local gray matter volume in prefrontal and cingulate cortex, and BDNF levels (trend). In conclusion, we showed that physical activity conveys the beneficial effects on memory function independently of its intensity, possibly mediated by local gray matter volume and neurotrophic factors. Our findings may carry significant implications for prevention of cognitive decline in the elderly.

Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy

AIMS To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain. METHODS AND RESULTS We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37-84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (ß = -0.115, P < 0.01) as well as attention and executive functions (ß = -0.105, P < 0.01) compared with subjects without AF. There was also a trend (P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups. CONCLUSION Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.

Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function

Objective: C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). Methods: We cross-sectionally examined 447 community-dwelling and stroke-free individuals from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study (mean age 63 years, 248 female). High-field MRI was performed in 321 of these subjects. Imaging measures included fluid-attenuated inversion recovery sequences for assessment of white matter hyperintensities, automated quantification of brain parenchyma volumes, and diffusion tensor imaging for calculation of global and regional white matter integrity, quantified by fractional anisotropy (FA). Psychometric analyses covered verbal memory, word fluency, and executive functions. Results: Higher levels of hs-CRP were associated with worse performance in executive function after adjustment for age, gender, education, and cardiovascular risk factors in multiple regression analysis (β = −0.095, p = 0.02). Moreover, higher hs-CRP was related to reduced global fractional anisotropy (β = −0.237, p < 0.001), as well as regional FA scores of the frontal lobes (β = −0.246, p < 0.001), the corona radiata (β = −0.222, p < 0.001), and the corpus callosum (β = −0.141, p = 0.016), in particular the genu (β = −0.174, p = 0.004). We did not observe a significant association of hs-CRP with measures of white matter hyperintensities or brain atrophy. Conclusion: These data suggest that low-grade inflammation as assessed by high-sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function.

Occult Atrial Fibrillation in Cryptogenic Stroke Detection by 7-Day Electrocardiogram Versus Implantable Cardiac Monitors

Background and Purpose— A significant number of patients with cryptogenic stroke suffer from intermittent atrial fibrillation (iAF) which was not detected during the standard diagnostic procedures. We investigated whether implantation of an insertable cardiac monitor (ICM) is feasible in patients with cryptogenic stroke, and compared the iAF detection rate of the ICM with 7-day Holter monitoring. Methods— Sixty patients (median age 63; interquartile range, 48.5–72 years) with acute cryptogenic stroke were included. ICM was implanted 13 days (interquartile range; 10–65 days) after the qualifying event. Seven-day Holter was performed after the ICM was implanted. Results— The iAF was detected by the ICM in 10 patients (17%; 95% CI, 7% to 26%). Only 1 patient (1.7%; 95% CI, 0% to 5%) had iAF during 7-day Holter monitoring as well (P=0.0077). Episodes of iAF lasting 2 minutes or more were detected 64 (range, 1–556) days after implantation. There were no recurrent strokes during the observation period. The implantation procedure was well tolerated with no adverse events; the daily data transmission protocol was easy to handle by the patients. Conclusions— ICM implantation for the detection of iAF during outpatient follow-up is feasible in patients with cryptogenic stroke. ICMs offer a much higher diagnostic yield than 7-day Holter monitoring.

Dehydration confounds the assessment of brain atrophy

Computerized brain volumetry has potential value for diagnosis and the follow-up evaluation of degenerative disorders. A potential pitfall of this method is the extent of physiologic variations in brain volume. The authors show that dehydration and rehydration can significantly change brain volume: lack of fluid intake for 16 hours decreased brain volume by 0.55% (SD, ±0.69), and after rehydration total cerebral volume increased by 0.72% (SD, ±0.21).

Nerve fiber impairment of anterior thalamocortical circuitry in juvenile myoclonic epilepsy

Background: Juvenile myoclonic epilepsy (JME) is a syndrome of idiopathic generalized epilepsy (IGE) without structural brain abnormalities detectable by MRI or CT. Objective: In the present study, we addressed the question of whether diffusion tensor MRI (DTI) can detect disease-specific white matter (WM) abnormalities in patients with JME. Methods: We performed whole head DTI at 3 T in 10 patients with JME, 8 age-matched patients with cryptogenic partial epilepsy (CPE), and 67 age-matched healthy volunteers. Nerve fiber integrity was compared between the groups on the basis of optimized voxel-by-voxel statistics of fractional anisotropy (FA) maps obtained by DTI (analysis of covariance, categorical factor “group,” covariate “age”). Results: FA was reduced in a WM region associated with the anterior thalamus and prefrontal cortex in patients with JME compared to both control subjects and patients with CPE (p < 0.001). The patients with CPE showed normal values in this particular WM region. The FA reductions in the patients with JME correlated with the frequency of generalized tonic-clonic seizures (Spearman R = 0.54, p = 0.05). No significant correlations were found in the JME sample between FA reduction and the duration of antiepileptic medication. Conclusions: The results support the hypothesis that juvenile myoclonic epilepsy is associated with abnormalities of the thalamocortical network that can be detected by diffusion tensor MRI. CPE = cryptogenic partial epilepsy; DTI = diffusion tensor imaging; EPI = echoplanar imaging; FA = fractional anisotropy; GMC = gray matter concentration; GTCS = generalized tonic-clonic seizures; IGE = idiopathic generalized epilepsy; JME = juvenile myoclonic epilepsy; MNI = Montreal Neurological Institute; ROI = region of interest; VBM = voxel based morphometry; WM = white matter.

High-Normal Blood Pressure Is Associated With Poor Cognitive Performance

While the relation between systolic blood pressure (SBP) and vascular events is linear down to the high-normal range, the relation between SBP and cognition is less clear. We cross-sectionally assessed the relation between SBP and cognition in a cohort extending from mid- to late-life. From a total of 2200 community-dwelling individuals we recruited 377 aged 44 to 82 years (median: 64 years, 171 male) in the SEARCH-Health study (Systematic evaluation and alteration of risk factors for cognitive health). Participants were studied with a comprehensive neuropsychological test battery that provided, based on principal component analysis, 5 composite scores for cognition (learning and memory, attention and executive function, spatial skills, working memory, and verbal skills). Global cognition was calculated from the sum of the composite scores. SBP (corrected R2=0.007), education (corrected R2=0.203), age (corrected R2=0.102), and gender (corrected R2=0.011) explained one third of variance in global cognitive performance (P<0.001) on multivariate analyses. Moreover, the relation between SBP (based on 10 mm Hg-categories from <120 mm Hg to >170 mm Hg) and global cognitive performance was linear in this range of SBP-values, ie, even in the normotensive range (β=−0.110, P<0.05). Subgroup analysis showed that the association of SBP and cognition was driven by results in midlife (<60 years) individuals (β=−0.291, P<0.005). Thus, even in the normotensive range increasing systolic blood pressure is inversely related to cognition.

Characteristics of Susac syndrome: a review of all reported cases

In Susac syndrome, occlusions of microvessels—presumed to be mediated by an autoimmune response to an as yet unknown antigen—lead to a characteristic clinical triad of CNS dysfunction, branch retinal artery occlusions, and sensorineural hearing impairment. Susac syndrome is considered a rare but important differential diagnosis in numerous neurological, psychiatric, ophthalmological, and ear, nose and throat disorders. Improved understanding of this disorder is crucial, therefore, to ensure that patients receive appropriate treatment and care. Current knowledge on Susac syndrome is largely based on reports of single patients, small case series, and nonsystematic reviews. The aim of this Review is to extend these previous, primarily anecdotal findings by compiling data from all 304 cases of Susac syndrome that have been published worldwide, which were identified following a literature search with predefined search, inclusion and exclusion criteria. From this data, we present an overview of demographic, clinical and diagnostic data on Susac syndrome, providing a reliable basis for our current understanding of this rare disease. Where possible, we make recommendations for clinical diagnosis, differential diagnosis, and management of patients with suspected Susac syndrome.

Hypoglycemia Aggravates Critical Illness-Induced Neurocognitive Dysfunction

OBJECTIVE Tight glycemic control (TGC) in critically ill patients is associated with an increased risk of hypoglycemia. Whether those short episodes of hypoglycemia are associated with adverse morbidity and mortality is a matter of discussion. Using a case-control study design, we investigated whether hypoglycemia under TGC causes permanent neurocognitive dysfunction in patients surviving critical illness. RESEARCH DESIGN AND METHODS From our patient data management system, we identified adult survivors treated for >72 h in our surgical intensive care unit (ICU) between 2004 and 2007 (n = 4,635) without a history of neurocognitive dysfunction or structural brain abnormalities who experienced at least one episode of hypoglycemia during treatment (hypo group) (n = 37). For each hypo group patient, one patient stringently matched for demographic- and disease-related data were identified as a control subject. We performed a battery of neuropsychological tests investigating five areas of cognitive functioning in both groups at least 1 year after ICU discharge. Test results were compared with data from healthy control subjects and between groups. RESULTS Critical illness caused neurocognitive dysfunction in all tested domains in both groups. The dysfunction was aggravated in hypo group patients in one domain, namely that of visuospatial skills (P < 0.01). Besides hypoglycemia, both hyperglycemia (r = −0.322; P = 0.005) and fluctuations of blood glucose (r = −0.309; P = 0.008) were associated with worse test results in this domain. CONCLUSIONS Hypoglycemia was found to aggravate critical illness–induced neurocognitive dysfunction to a limited, but significant, extent; however, an impact of hyperglycemia and fluctuations of blood glucose on neurocognitive function cannot be excluded.

A brief review of Susac syndrome.

Susac syndrome was named after J.O. Susac who first described the syndrome in 1979. It is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. It mainly occurs in young women. This underdiagnosed disease needs to be considered in the differential diagnosis of a broad variety of disorders. In Susac syndrome, autoimmune processes leading to damage and inflammation-related occlusion of the microvessels in brain, retina, and inner ear are thought to play a causal role. The diagnosis is based primarily on the clinical presentation, the documentation of branch retinal artery occlusion by fluorescence angiography, and characteristic findings on cerebral MRI, that help in distinguishing Susac syndrome from other inflammatory entities, like multiple sclerosis. Antiendothelial cell antibodies could be detected in some patients. Patients are successfully treated with immunosuppression, however, the best regimen still needs to be defined. As a result of the rarity of the disease, controlled therapeutic trials are missing so far. In this review, we want to demonstrate the clinical features, natural history, treatment, and clinical course of Susac syndrome, illustrated by a typical case history.