Depression and anxiety in acute ischemic stroke involving the anterior but not paramedian or inferolateral thalamus.

Background and objectives: Emotional and cognitive deficits are prevalent in strokes involving the thalamus. In contrast to cognitive deficits, emotional deficits have not been studied prospectively in isolated thalamic stroke. Methods: In 37 ischemic thalamic stroke patients (57.0 [50.0; 69.5] years [median (Q1; Q3)], 21 males, 5 anterior, 12 paramedian, 20 inferolateral vascular territory), and 37 non-stroke control patients matched for age and sex, we prospectively examined depression, anxiety, activities of daily living, and quality of life at 1, 6, 12, and 24 months post-stroke using the Hospital-Anxiety-and-Depression Scale (HADS), Nürnberger-Alters-Alltagsaktivitäten scale (NAA), and Short Form-36 (SF36) questionnaire. Voxel-based lesion-symptom mapping (VLSM) and lesion-subtraction analyzes were performed to determine associations between questionnaire scores and thalamic stroke topography. Results: At 1 month post-stroke, anterior thalamic stroke patients had higher depression scores [8.0 (7.5; 10.5)] than paramedian [4.5 (1.0; 5.8)] and inferolateral [4.0 (1.0; 7.0)] thalamic stroke patients. Furthermore, anterior thalamic stroke patients had higher anxiety scores [11.0 (8.0; 14.5)] than their matched controls [2.5 (2.0; 2.5)], paramedian [4.5 (1.0; 5.8)] and inferior [4.0 (1.0; 7.0)] thalamic stroke patients. Depression and anxiety scores in anterior thalamic stroke patients remained high across the follow-up [depression: 9.0 (3.5; 13,8); anxiety:10.05 (2.8, 14.5)].Physical health assessed by SF36 was intact in anterior [1 month post-stroke: T-score = 55.9 (37.0; 57.6)] but reduced in inferolateral [44.5(32.4; 53.1)] thalamic stroke, whereas mental health was reduced in anterior thalamic stroke [32.0 (29.8; 47.3)].VLSM confirmed that voxels in the anterior thalamus around Montreal Neurological Institute (MNI) coordinates X = -8, Y = -12, Z = 2 were more often affected by the stroke in depressed (HADS-score ≥ 8) than non-depressed (HADS-score < 8) patients and voxels around coordinates X = -10, Y = -12, Z = 2 were more often affected in anxious (HADS-score ≥ 8) than non-anxious (HADS-score < 8) patients. Conclusion: Anterior, but not paramedian or inferolateral thalamic stroke was associated with depression and anxiety. Even though our results are mostly significant in the left thalamus, this observation on stroke laterality might be confounded by the fact that the right hemisphere was underrepresented in our study.

Evolution of Neuropsychological Deficits in First-Ever Isolated Ischemic Thalamic Stroke and Their Association With Stroke Topography: A Case-Control Study.

BACKGROUND: The thalamus plays an essential role in cognition. Cognitive deficits have to date mostly been studied retrospectively in chronic thalamic stroke in small cohorts. Studies prospectively evaluating the evolution of cognitive deficits and their association with thalamic stroke topography are lacking. This knowledge is relevant for targeted patient diagnostics and rehabilitation. METHODS: Thirty-seven patients (57.5±17.5 [mean±SD] years, 57% men) with first-ever acute isolated ischemic stroke covering the anterior (n=5), paramedian (n=12), or inferolateral (n=20) thalamus and 37 in-patient controls without stroke with similar vascular risk factors matched for age and sex were prospectively studied. Cognition was evaluated using predefined tests at 1, 6, 12, and 24 months. Voxel-based lesion-symptom mapping was used to determine associations between neuropsychological deficits and stroke topography. RESULTS: Patients with anterior thalamic stroke revealed severe deficits in verbal memory (median T score [Q1-Q3]: 39.1 [36.1-44.1]), language (31.8 [31.0-43.8]), and executive functions (43.8 [35.5-48.1]) at 1 month compared with controls (verbal memory: 48.5 [43.6-61.0], language: 55.7 [42.3-61.1], executive functions: 51.3 [50.1-56.8]). Patients with paramedian thalamic stroke showed moderate language (44.7 [42.8-55.9]) and executive (49.5 [44.3-55.1]) deficits and no verbal memory deficits (48.1 [42.5-54.7]) at 1 month compared with controls (59.0 [47.0-64.5]; 59.6 [51.1-61.3]; 52.5 [44.2-55.3]). The language and executive deficits in paramedian thalamic stroke patients almost completely recovered during follow-up. Intriguingly, significant deficits in verbal memory (44.7 [41.5-51.9]), language (47.5 [41.8-54.1]), and executive functions (48.2 [46.2-59.7]) were found in inferolateral thalamic stroke patients at 1 month compared with controls (50.5 [46.7-59.9]; 57.0 [51.2-62.9]; 57.4 [51.2-60.7]). Language, but not executive deficits persisted during follow-up. Voxel-based lesion-symptom mapping revealed an association of verbal memory deficits with anterior thalamus lesions and an association of non-verbal memory, language, and executive deficits with lesions at the anterior/paramedian/inferolateral border. CONCLUSIONS: All 3 stroke topographies exhibited significant deficits in diverse cognitive domains, which recovered to a different degree depending on the stroke localization. Our study emphasizes the need for comprehensive neuropsychological diagnostics to secure adequate patient rehabilitation.

Association of Plasma ß-Amyloid with Cognitive Performance and Decline in Chronic Kidney Disease.

Decreased ß-amyloid (Aß) clearance from the brain has been suggested to contribute to cerebral Aß accumulation in Alzheimer's disease. Based on the idea of a dynamic Aß equilibrium in different body compartments, plasma Aß levels have been investigated as biomarker candidates for preclinical Alzheimer's pathology, yet with inconsistent results. Since the kidneys are involved in Aß elimination from the blood, we evaluated how chronic kidney disease (CKD) affects the association between plasma Aß and cognitive deficits and cognitive decline. In 28 CKD patients, stages 3-5D, and 26 control subjects with comparable vascular risk profile from the New Tools for the Prevention of Cardiovascular Disease in Chronic Kidney Disease (NTCVD) cohort, plasma total Aß was determined with a highly sensitive electrochemiluminescence immunoassay. Cognition was evaluated using a comprehensive battery of ten neuropsychological tests at baseline and 2-year follow-up. Subjects with high plasma Aß level (above median) demonstrated a significantly worse baseline cognitive performance than subjects exhibiting low Aß level (summary score of global cognitive performance at baseline z = -0.46 ± 0.76 vs z = -0.08 ± 0.57, p = 0.045). Cognitive performance moderately decreased over the 2-year follow-up in subjects with high plasma Aß level (Δz = -0.13 ± 0.51), but increased in subjects with low plasma Aß level (Δz = 0.16 ± 0.41, p = 0.023). In linear regression analyses, baseline plasma Aß was significantly associated with cognitive decline both in unadjusted analyses (ß = -0.28, 95% CI = -0.55 to -0.01) and analyses adjusted for age (ß = -0.27, 95% CI = -0.54 to -0.01). Our results suggest the utility of plasma Aß level in predicting cognitive decline in patients suffering from CKD.

Cognitive Performance Is Highly Stable over a 2-Year-Follow-Up in Chronic Kidney Disease Patients in a Dedicated Medical Environment.

BACKGROUND: As kidney and brain functions decline with aging, chronic kidney disease (CKD) and dementia are becoming increasing health burdens worldwide. Among the risk factors for cognitive impairment, CKD is increasingly recognized. The precise impact of CKD on the development of cognitive impairment is poorly understood. METHODS: In the New Tools for the Prevention of Cardiovascular Disease in Chronic Kidney Disease (NTCVD) cohort, which was recruited in a dedicated nephrology department, we examined the 2-year course of cognitive performance in 120 patients (73 patients with CKD stages 3-5D, 47 control patients without CKD with similar vascular risk profile) using a comprehensive battery of 10 neuropsychological tests. RESULTS: Kidney function, vascular risk factors and cognitive performance were highly stable both in CKD and control patients. The summary score of cognitive performance in CKD patients was very similar at baseline (z = -0.63±0.76) and follow-up (z = -0.54±0.79, p = 0.113), as was cognitive performance in control patients (z = -0.01±0.59 and 0.01±0.70, p = 0.862, at baseline and follow-up, respectively). Total serum cholesterol (199.6±36.0 and 186.0±32.9, p = 0.005 in controls; 194.4±46.1 and 181.2±41.2, p = 0.008 in CKD) and common carotid intima-media thickness (0.87±0.18 and 0.84±0.17, p = 0.351 in controls; 0.88±0.21 and 0.82±0.16, p = 0.002 in CKD) moderately but significantly decreased during the follow-up. In multivariable regression analyses, high age (ß = -0.28, 95%CI = -0.48 to 0.08, p = 0.007) predicted decrease in cognitive performance. CONCLUSIONS: In this well-defined cohort receiving state-of-the-art therapy, cognitive performance did not decrease over 2 years. Our data emphasize the aspect of risk factor control, suggesting that dedicated medical care might prevent cognitive decline in CKD patients.

Factors Responsible for Plasma ß-Amyloid Accumulation in Chronic Kidney Disease.

Disturbed brain-to-blood elimination of ß-amyloid (Aß) promotes cerebral Aß accumulation in Alzheimer's disease. Considering that the kidneys are involved in Aß elimination from the blood, we evaluated how chronic kidney disease (CKD) affects plasma Aß. In 106 CKD patients stages 3-5 (including 19 patients on hemodialysis and 15 kidney recipients), 53 control subjects with comparable vascular risk profile and 10 kidney donors, plasma Aß was determined using electrochemiluminescence immunoassay and gel electrophoresis followed by Western blotting. Plasma Aß increased with CKD stage (control = 182.98 ± 76.73 pg/ml; CKD3A = 248.34 ± 103.77 pg/ml; CKD3B = 259.25 ± 97.74 pg/ml; CKD4 = 489.16 ± 154.16 pg/ml; CKD5 = 721.19 ± 291.69 pg/ml) and was not influenced by hemodialysis (CKD5D = 697.97 ± 265.91 pg/ml). Renal transplantation reduced plasma Aß (332.57 ± 162.82 pg/ml), whereas kidney donation increased it (251.51 ± 34.34 pg/ml). Gel electrophoresis confirmed stage-dependent elevation namely of Aß1-40, the most abundant Aß peptide. In a multivariable regression including age, sex, estimated glomerular filtration rate (eGFR), potassium, hemoglobin, urine urea, and urine total protein, the factors eGFR (ß = -0.42, p < 0.001), hemoglobin (ß = -0.17, p = 0.020), and urine protein (ß = 0.26, p = 0.008) were associated with plasma Aß. In a regression including age, sex, eGFR, potassium, hemoglobin and the vascular risk factors systolic blood pressure, smoking, LDL, HDL, HbA1c, body mass index, brain-derived natriuretic peptide and fibrinogen, the factors eGFR (ß = -0.53, p < 0.001), body mass index (ß = -0.17, p = 0.022), and fibrinogen (ß = 0.18, p = 0.024) were associated with plasma Aß. Our results demonstrate a stage-dependent plasma Aß increase that is augmented by loss of glomerulotubular integrity, low body weight, and inflammation, demonstrating a multifaceted role of renal dysfunction in Aß retention.

Physical, cognitive and emotional factors contributing to quality of life, functional health and participation in community dwelling in chronic kidney disease.

BACKGROUND: Quality of life (QoL) impairment is a well-known consequence of chronic kidney disease (CKD). The factors influencing QoL and late life functional health are poorly examined. METHODS: Using questionnaires combined with neuropsychological examinations, we prospectively evaluated physical, cognitive, and emotional factors influencing QoL, functional health and participation in community dwelling in 119 patients with CKD stages 3-5 including hemodialysis (61.5±15.7years; 63% men) and 54 control patients of the same age without CKD but with similar cardiovascular risk profile. RESULTS: Compared with control patients, CKD patients showed impairment of the physical component of QoL and overall function, assessed by the SF-36 and LLFDI, whereas disability, assessed by LLFDI, was selectively impaired in CKD patients on hemodialysis. Multivariable linear regressions (forced entry) confirmed earlier findings that CKD stage (ß = -0.24; p = 0.012) and depression (ß = -0.30; p = 0.009) predicted the QoL physical component. Hitherto unknown, CKD stage (ß = -0.23; p = 0.007), cognition (ß = 0.20; p = 0.018), and depression (ß = -0.51; <0.001) predicted disability assessed by the LLFDI, while age (ß = -0.20; p = 0.023), male gender (B = 5.01; p = 0.004), CKD stage (ß = -0.23; p = 0.005), stroke history (B = -9.00; p = 0.034), and depression (ß = -0.41; p<0.001) predicted overall function. Interestingly, functional health deficits, cognitive disturbances, depression, and anxiety were evident almost only in CKD patients with coronary heart disease (found in 34.2% of CKD patients). The physical component of QoL and functional health decreased with age and depressive symptoms, and increased with cognitive abilities. CONCLUSIONS: In CKD, QoL, functional health, and participation in community dwelling are influenced by physical, cognitive, and emotional factors, most prominently in coronary heart disease patients.

The prevalence, severity, and association with HbA1c and fibrinogen of cognitive impairment in chronic kidney disease.

Cognitive impairment is a frequent finding in patients with chronic kidney disease (CKD). We examined cognitive performance in a prospective study of 119 patients with CKD stages 3-5 (including dialysis) and 54 control patients of the same age without CKD but with similar vascular risk profiles. Analysis included a comprehensive test battery evaluating memory, information processing speed, executive function, language, and visuoconstructive function, in addition to depression and anxiety. Thirty percent of patients with CKD had cognitive deficits (one or more s.d. below control patient performance). Cognitive deficits (T-value related to published norm values) were mild but significantly decreased to 48.8 in patients with stage 3-5 CKD not requiring hemodialysis and 47.2 in patients with stage 5D disease requiring hemodialysis, compared with 51.5 in control patients. Linear regressions among patients with CKD (forced entry strategy) showed that age (ß=-0.50 per s.d.), HbA1c (ß=-0.18 per s.d.), and fibrinogen (ß=-0.18 per s.d.) predicted cognitive performance. Interestingly, HbA1c discriminated cognition in all age groups, while fibrinogen differentiated cognition particularly in patients over 70 years of age. Thus, our cross-sectional study suggests the severity of cognitive impairment in CKD is mild. As such, longitudinal studies are required to further characterize the role of cognitive deficits in CKD.

Neuropsychological disturbances in frontal lobe epilepsy due to mutated nicotinic receptors.

Mutations in nicotinic receptor subunits have been identified in some families with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Normal intelligence has currently been considered the rule, although anecdotal cases with intellectual disability have been reported. We aimed to evaluate the frequency and degree of neuropsychological disorders in ADNFLE associated with nicotinic receptor mutations by testing 11 subjects from four families with a comprehensive neuropsychological assessment. General intellectual function was below the normal range in 45% of the subjects. All were abnormal in one or more executive task. Memory was either more affected than executive functions or equally affected in two thirds of subjects, suggesting a frontotemporal pattern of cognitive impairment. Cognitive dysfunction appears to be an integral part of the broad phenotype of ADNFLE with nicotinic receptor mutations, a fact that has been underestimated until now. The cognitive disorder affects executive functions as well as memory in most subjects.

Patients with chronic focal cerebellar lesions show no cognitive abnormalities in a bedside test.

The aim of the present study was to show whether cognitive deficits are present in chronic cerebellar patients using a self-developed, validated bedside screening test. Twenty-one adults with a history of infarction within the territory of the posterior-inferior (PICA) or the superior cerebellar artery (SCA), and 25 age-, sex-, and education-matched healthy controls participated. Lesion localization was based on individual 3D MRI scans. The test took 10-12 min including subtests of naming, executive functions, attention, figural and verbal memory, reading, long-term memory, mental arithmetic, higher order motor control, and spatial functions. Though individual patients tended to make more errors than controls, neither total error score nor subscores revealed significant group differences. No obvious cognitive deficits appeared to be present in chronic cerebellar patients as assessed by a bedside screening test.