Elderly Controls Research Articles

EFEKTIVITAS TERAPI RELAKSASI OTOT PROGRESIF DALAM MENURUNKAN HIPERTENSI PADA LANSIA

The prevalence of cases of hypertension is very high in the elderly, namely 60% -80% at the age above 65 years. The number of elderly people suffering from hypertension at Budi Luhur Jambi PSTW in November 2018 was 22 elderly and had received regular hypertension medication every day but the elderly blood pressure was still high. The purpose of this study is to see whether there is any effect of progressive muscle relaxation therapy on blood pressure in elderly people with hypertension. This study used the Quasi Experiment method with the design of Non Equivalent Control Group Pretest-Posttest, with random sampling technique, the number of samples was 20 elderly consisting of 10 elderly experimental groups given hypertension drugs as well as progressive muscle relaxation therapy and 10 elderly control groups who only given hypertension medication. This research was conducted at Budi Luhur PSTW Jambi on 28 January-2 February 2019. Progressive muscle relaxation therapy is given once a day every morning for six consecutive days. Based on the analysis using the Dependent T test in the experimental group, it was found that systolic blood pressure was p value 0.0001 and diastolic blood pressure was p value 0.002 <(0.05). the results of the analysis using the Independent T test found differences in the blood pressure of the experimental group and control where systolic blood pressure p value 0.031 <(0.05), while the diastolic blood pressure p value 0.009 <(0.05), it can be concluded that there significant to the blood pressure of elderly people with hypertension before and after being given progressive muscle relaxation therapy. This study is expected to be a new program at PSTW Budi Luhur Jambi to reduce high blood pressure in elderly people who suffer from hypertension.

Prophylactic implantable cardioverter-defibrillator in the very elderly.

Current guidelines do not propose any age cut-off for the primary prevention implantable cardioverter-defibrillator (ICD). However, the risk/benefit balance in the very elderly population has not been well studied. In a multicentre French study assessing patients implanted with an ICD for primary prevention, outcomes among patients aged ≥80 years were compared with <80 years old controls matched for sex and underlying heart disease (ischaemic and dilated cardiomyopathy). A total of 300 ICD recipients were enrolled in this specific analysis, including 150 patients ≥80 years (mean age 81.9 ± 2.0 years; 86.7% males) and 150 controls (mean age 61.8 ± 10.8 years). Among older patients, 92 (75.6%) had no more than one associated comorbidity. Most subjects in the elderly group got an ICD as part of a cardiac resynchronization therapy procedure (74% vs. 46%, P < 0.0001). After a mean follow-up of 3.0 ± 2 years, 53 patients (35%) in the elderly group died, including 38.2% from non cardiovascular causes of death. Similar proportion of patients received ≥1 appropriate therapy (19.4% vs. 21.6%; P = 0.65) in the elderly group and controls, respectively. There was a trend towards more early perioperative events (P = 0.10) in the elderly, with no significant increase in late complications (P = 0.73). Primary prevention ICD recipients ≥80 years in the real world had relatively low associated comorbidity. Rates of appropriate therapies and device-related complications were similar, compared with younger subjects. Nevertheless, the inherent limitations in interpreting observational data on this particular competing risk situation call for randomized controlled trials to provide definitive answers. Meanwhile, a careful multidisciplinary evaluation is needed to guide patient selection for ICD implantation in the elderly population.

ApoE4 lowers age at onset in patients with frontotemporal dementia and tauopathy independent of amyloid-β copathology

IntroductionApolipoprotein E (ApoE) is the most important genetic risk factor for Alzheimer's disease (AD), with ApoE4 thought to enhance and accelerate amyloid-β (Aβ) pathology. ApoE4 has recently been described to increase neurodegeneration in a mouse model of frontotemporal dementia (FTD), in vitro, and in patients, demonstrating that ApoE4 modifies tauopathy independently of Aβ. This raises the question whether ApoE genotype also modifies the clinical phenotype in patients with FTD with tau pathology. MethodsWe analyzed 704 patients with FTD, including a genetically and neuropathologically confirmed subset, and 452 healthy elderly controls. We compared ApoE4 genotype frequency and age at onset in tau+ or TDP43+ FTD patients with or without Aβ copathology. ResultsThe ApoE4 genotype lowered age at onset in patients with FTD and tau pathology, particularly once accounting for confounding effects of Aβ pathology. DiscussionWe conclude that ApoE4 accelerates neurodegeneration in FTD patients with MAPT mutations or FTLD-tau pathology, independent of Aβ.

Spontaneous spatial information provided by dementia patients and elderly controls in narratives

Patients diagnosed with dementia of the Alzheimer’s type (DAT) often show two symptoms early on: the inability to navigate space effectively and a deterioration of their language skills, especially on semantic tasks. In this work, I look at whether the inability to navigate space is reflected in the spontaneous speech of DAT patients. Through a corpus analysis of narratives by DAT and control participants, I investigate the hypothesis that DAT patients provide less spatial information than healthy controls (mirroring the decline of effective spatial reasoning in language production). This hypothesis was not supported for locative/stative descriptions using in, on, and at; both groups included this information equally often. However, significant differences between the groups were found for the inclusion of the spatial terms left and right as well directional/dynamic spatial information indicated by into, onto, from, and to. This difference between locative/stative and directional/dynamic spatial information has not previously been reported. I argue that it aligns with Chatterjee’s (2008) proposal of the relational features of spatial language and that these features can be differently affected in DAT patients, aligning it with the spatial navigation impairment in these participants.

The use of motor imagery training to retain the performance improvement following physical practice in the elderly.

With physiological aging, appears a deterioration of the ability to retain motor skills newly acquired. In this study, we tested the beneficial role of motor imagery training to compensate this deterioration. We tested four groups: young control group (n = 10), elderly control group (n = 10), young mental-training group (n = 13) and elderly mental-training group (n = 13). In pre- and post-tests, the participants performed three trials on a dexterity manual task (the Nine Hole Peg Test), commonly used in clinic. We recorded the movement duration as a factor of performance. Each trial, including 36 arm movements, consisted in manipulating sticks as fast as possible. The control groups watched a non-emotional documentary for 30min and the mental-training groups imagined the task (50 trials). First, we observed a speed improvement during the pre-test session for all groups. Immediately after viewing the movie (post-test 1), the young control group showed a preservation of motor performance in comparison to the performance measured before the break (pret-test 3), while the young mental-training group improved performance after motor imagery practice. For the elderly, the control group showed a deterioration of motor performance at post-test 1, attesting a deterioration of the ability to retain motor skills with aging. Interestingly, the elderly mental-training group showed a preservation of motor performance between the pre-test 3 and the post-test 1. The present findings demonstrate the beneficial role of mental training with motor imagery to retain the performance improvement following physical practice in the elderly. This method could be an alternative to prevent the deterioration of motor skills.

Connection between Static and Dynamic Balance during Dual Task Performance

Research background. There are up to 60 percent of community dwelling elderly people which experience falls due to cognitive impairment. It also affects the motor function, especially the balance control. In everyday life, it is often necessary to perform several motor and cognitive tasks at the same time, therefore, the relationship between the risk of falling and cognitive function is very close. A very noticeable change in cognitive function can lead to inappropriate decision making, attention disturbances, which can increase the risk of falls. The aim of the research. To assess the interaction between community dwelling elderly people balance control and cognitive functions. Methods. The evaluation of static balance using “Kistler” platform, the evaluation of dynamic balance with the “Timed Up &amp; Go” test, dual task method. Results. The results showed that the maintenance of static balance deteriorated while performing a cognitive task at the same time in community dwelling people. Dynamic balance control also deteriorated in elderly people while performing a cognitive task, and the subjects went slower 3 meters under such conditions. A cognitive task signifcantly prolonged “Timed Up &amp; Go” test results of dynamic balance. A signifcant interaction between static and dynamic balance control was found while performing a cognitive task. Conclusions. 1) static balance control of the community dwelling elderly people statistically signifcantly deteriorated while performing cognitive task, without visual feedback and also in romberg’s standing position; 2) dynamic balance control of the community dwelling elderly people statistically signifcantly deteriorated while performing cognitive task; 3) a statistically signifcant direct relation was found between static and dynamic balance behaviour while performing a cognitive task in both cases, the balance control is deteriorating.Keywords: balance control, older age, static balance, dynamic balance.

Motion-induced position mis-localization predicts the severity of Alzheimer's disease.

Patients with Alzheimer's disease (AD) often exhibit motion processing deficits. It is unclear whether the localization of moving objects - a perceptual process tightly linked to motion - is impaired or intact in AD. In this study, we used the phenomenon of illusory shift of position induced by motion as a behavioural paradigm to probe how the spatial representation differs between AD patients and healthy elderly controls. We measured the magnitudes of motion-induced position shift in a group of AD participants (N=24) and age-matched elderly observers (N=24). We found that AD patients showed weakened position mis-localization, but only for motion stimuli of slow speeds. For fast motion, the position mis-localization did not differ significantly between groups. Furthermore, we showed that the magnitudes of position mis-localization can predict the severity of AD; that is, patients with more severe symptoms had less preserved position mis-localization. Our results suggest that AD pathology impacts not only motion processing per se, but also the perceptual process related to motion such as the localization of moving objects.

Prevalence of C9ORF72 Expansion in a Large Series of Patients with Idiopathic Normal-Pressure Hydrocephalus

Background/Aims: The C9ORF72 expansion is known to cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We aim to identify the prevalence of the C9ORF72 expansion in idiopathic normal pressure hydrocephalus (iNPH). Methods: We analysed the C9ORF72 expansion in a large cohort of patients with possible iNPH (n = 487) and cognitively intact elderly controls (n = 432; age > 65 years). Results: While the C9ORF72 expansion was detected in 1.6% (n = 8/487) of cases with possible iNPH, no control subject was found to carry the mutation. The mean age at onset of symptoms of C9ORF72 expansion carriers was 59 years (range: 52–67 years), 11 years less than non-carriers (p = 0.0002). The most frequent initial/main symptom pertained to gait difficulties. Despite identified mutation, only 3 of the patients fulfilled the criteria for the FTLD-ALS spectrum. Clinically significant shunt response was detected in 6 out of 7 shunted C9ORF72 expansion carriers. Conclusion: This is the first study cohort identifying the underlying C9ORF72 expansion in patients with iNPH providing evidence for the potential comorbidity between iNPH and the FTLD-ALS spectrum. Analysis of the C9ORF72 expansion should be considered for patients with probable iNPH presenting with frontal atrophy and personality changes or other severe psychiatric symptoms.

Distinctive and Pervasive Alterations of Functional Brain Networks in Cerebral Small Vessel Disease with and without Cognitive Impairment

Objective: To explore the within- and between-network patterns of the default mode network (DMN), the frontoparietal control network (FPCN), and the dorsal attention network (DAN) in cerebral small vessel disease (CSVD) with and without cognitive impairment (CI). Methods: Twenty CSVD with CI subjects, 21 CSVD without CI subjects, and 25 healthy elderly controls were recruited. The within- and between-network patterns of the networks were identified based on resting-state functional magnetic resonance imaging data. Results: Compared with the control group, both the CSVD with CI group and the CSVD without CI group displayed decreased within-network function of the DMN and lower negative connectivity between the DMN and other networks (i.e., DMN and DAN, DMN and FPCN), whereas the CSVD with CI group additionally showed within- and between-network alterations of the FPCN (i.e., increased within-network function of the FPCN and lower negative connectivity between the FPCN and the DMN). Furthermore, these alterations of the FPCN were correlated with the cognitive function of CSVD subjects. Interestingly, the between-network connectivity of the FPCN and the DMN was negatively correlated with deep white matter hyperintensities (DWMH) volume in CSVD subjects. Conclusion: These findings suggest that cognitive alterations of CSVD subjects may be mainly regulated by the FPCN that correlates with DWMH burden, and shed light on the investigation of surrogate markers of CSVD.

Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue

[F-18]-MK-6240, a novel tau positron emission tomography (PET) tracer recently discovered for the in vivo detection of neurofibrillary tangles, has the potential to improve diagnostic accuracy in the detection of Alzheimer disease. We have examined regional and substrate-specific binding patterns as well as possible off-target binding of this tracer on human brain tissue to advance towards its validation. We applied [F-18]-MK-6240 phosphor screen and high resolution autoradiography to postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau (Pick’s disease, progressive supranuclear palsy and corticobasal degeneration), chronic traumatic encephalopathy, frontotemporal lobar degeneration-Tar DNA-binding protein 43 (TDP-43), dementia with Lewy bodies, cerebral amyloid angiopathy and elderly controls free of pathologic changes of neurodegenerative disease. We also directly compared the binding properties of [F-18]-MK-6240 and [F-18]-AV-1451 in human tissue, and examined potential nonspecific binding of both tau tracers to monoamine oxidases (MAO) by using autoradiography in the presence of selective monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitors. Our data indicate that MK-6240 strongly binds to neurofibrillary tangles in Alzheimer disease but does not seem to bind to a significant extent to tau aggregates in non-Alzheimer tauopathies, suggesting that it may have a limited utility for the in vivo detection of these pathologies. There is no evidence of binding to lesions containing β-amyloid, α-synuclein or TDP-43. In addition, we identified MK-6240 strong off-target binding to neuromelanin and melanin-containing cells, and some weaker binding to areas of hemorrhage. These binding patterns are nearly identical to those previously reported by our group and others for [F-18]-AV-1451. Of note, [F-18]-MK-6240 and [F-18]-AV-1451 autoradiographic binding signals were only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline, suggesting that MAO enzymes do not appear to be a significant binding target of any of these two tracers. Together these novel findings provide relevant insights for the correct interpretation of in vivo [F-18]-MK-6240 PET imaging.

Impaired comprehension of metaphorical expressions in very mild Alzheimer's disease.

BackgroundBrain-damaged patients often have difficulty understanding non-literal language. However, whether patients with Alzheimer’s disease (AD) have comprehension deficits of metaphorical expressions, in contrast with non-metaphorical (literal) expressions, remains unclear.Patients and methodsThe subjects were 40 AD patients; 20 had mild AD (17–23 points on the Mini-Mental State Examination [MMSE]), and 20 had very mild AD (≥24 points). Twenty normal elderly controls were also enrolled as a control group. Thirty sentences that contained novel similes (Items) were prepared. For each Item, four explanatory choices, consisting of one correct response and three foils, were provided. The participants were asked to choose the written statement that best represented the Item’s meaning. In addition, all the subjects completed the Token Test.ResultsThe patients with mild AD had significantly lower scores than the normal controls on both the simile comprehension test and the Token Test. However, the patients with very mild AD exhibited significantly lower scores on the simile comprehension test, but not on the Token Test. The distributions of error types for the simile test differed between the mild AD group and the other groups. The mild AD patients made more errors that were “far” from the correct responses.ConclusionPatients with AD are more likely to have comprehension deficits of metaphorical expressions than comprehension deficits of non-metaphorical expressions. Pragmatic language dysfunction may precede formal language dysfunction during the progression of AD.

Age-dependent impairment of the erythropoietin response to reduced central venous pressure in HFpEF patients.

Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), it remains unknown whether central hemodynamic alterations inherently present in this condition do affect blood pressure and blood volume (BV) regulation. The present study sought to determine hemodynamic and endocrine responses to prolonged orthostatic stress in HFpEF patients. Central venous pressure (CVP) assessed via the internal jugular vein (IJV) aspect ratio with ultrasonography, arterial pressure and heart rate were determined at supine rest and during 2 hours of moderate (25–30°) head‐up tilt (HUT) in 18 stable HFpEF patients (71.2 ± 7.3 years), 14 elderly (EC), and 10 young (YC) healthy controls. Parallel endocrine measurements comprised main BV‐regulating hormones: pro‐atrial natriuretic peptide, copeptin, aldosterone, and erythropoietin (EPO). At supine rest, the IJV aspect ratio was higher (>30%) in HFpEF patients compared with EC and YC, while mean arterial pressure was elevated in HFpEF patients (98.0 ± 13.1 mm Hg) and EC (95.6 ± 8.3 mm Hg) versus YC (87.3 ± 5.0 mm Hg) (P < 0.05). HUT increased heart rate (+10%) and reduced the IJV aspect ratio (−52%), with similar hemodynamic effects in all groups (P for interaction ≥ 0.322). The analysis of endocrine responses to HUT revealed a group×time interaction for circulating EPO, which was increased in YC (+10%) but remained unaltered in HFpEF patients and EC. The EPO response to a given reduction in CVP is similarly impaired in HFpEF patients and elderly controls, suggesting an age‐dependent dissociation of EPO production from hemodynamic regulation in the HFpEF condition.

Investigating the perceived timing of sensory events triggering actions in patients with Parkinson's disease and the effects of dopaminergic therapy

Few studies have investigated if Parkinson's disease (PD), advancing age, or exogenous dopamine therapy affect the perceived timing of past events. Here we show a phenomenon of ‘temporal repulsion’ of a sensory event relative to an action decision in patients with PD. In these patients, the timing of a sensory event triggering an action was perceived to have occurred earlier in time than it really did. In other words, the event appeared to be pushed away in time from the performance of the action. This finding stands in sharp contrast to the ‘temporal binding’ we have observed here and elsewhere (Yabe et al., 2017; Yabe & Goodale, 2015) in young healthy participants for whom the perceived onset of a sensory event triggering an action is typically delayed, as if it were pulled towards the action in time. In elderly patients, sensory events were neither repulsed nor pulled toward the action decision event. Exogenous dopamine alleviated the temporal repulsion in PD patients and normalized the temporal binding in healthy elderly controls. In contrast, dopaminergic therapy worsened temporal binding in healthy young participants. We discuss this pattern of findings, relating temporal binding processes to dopaminergic and striatal mechanisms.

Deficits of visuospatial working memory and executive function in single- versus multiple-domain amnestic mild cognitive impairment: A combined ERP and sLORETA study

ObjectiveAccording to recent criteria of classification, amnestic mild cognitive impairment (aMCI) could be divided into two categories: single-domain aMCI (sd-aMCI) and multiple-domain aMCI (md-aMCI). The difference between sd-aMCI and md-aMCI needs further exploration. The present study aimed to compare deficits in visuospatial working memory (VSWM) and executive function between sd-aMCI versus md-aMCI patients by use of event-related potentials (ERP) and standardized low-resolution brain electromagnetic tomography analysis (sLORETA). MethodsThe ERP data were measured and analyzed in 26 sd-aMCI, 13 md-aMCI patients and 46 healthy elderly controls (HEC) during VSWM and Go/Nogo processes. ResultsDuring VSWM task, md-aMCI patients showed decreased P300 amplitude compared to HEC and sd-aMCI patients (All p < 0.05). As compared to sd-aMCI, md-aMCI showed a hypoactivation in the right middle frontal gyrus in 1-back task during the P300 time range. During the Go/Nogo task, sd-aMCI and md-aMCI patients showed reduced N200 amplitude, compared to HEC (All p < 0.05). However, md-aMCI patients had decreased N200 amplitude, with respect to sd-aMCI patients. Further, as compared to sd-aMCI patients, md-aMCI patients showed a hypoactivation in the right superior frontal gyrus during the N200 time range. ConclusionsThese findings with a combined ERP and sLORETA study showed more severe deficits in updating operations of WM, detections of the target stimulus and conflict processes in md-aMCI, compared to sd-aMCI patients. SignificanceThe present study showed that a combined ERP and sLORETA study during the VSWM and Go/Nogo tasks could distinguish md-aMCI from sd-aMCI.

Breadth and depth of working memory and executive function compromises in mild cognitive impairment and their relationships to frontal lobe morphometry and functional competence

IntroductionThe extent of working memory (WM) and executive function (EF) impairment in mild cognitive impairment (MCI) is not well-characterized. MethodsWe compared 48 patients with MCI, 124 noncognitively impaired elderly healthy controls, and 57 patients with Alzheimer's disease (AD) on multiple WM/EF measures, frontal lobe integrity indexes, and functioning. ResultsPatients with MCI demonstrated worse performance on nearly all WM/EF tests. This profile of impairment was refined in a factor analysis that identified three primary WM/EF constructs: WM storage; speed and controlled visual search; and manipulation of information and problem solving. EF impairments were associated with reductions in prefrontal cortical thickness. WM/EF accounted for over 50% of the variance in functional competence. DiscussionIn MCI, WM/EF impairments are far from rare, based on specific compromises to frontal cortex circuitry, and are associated with loss of everyday functioning. WM/EF impairments, even at this potentially prodromal stage of AD, have clinically deleterious consequences.

Gut microbiota-dependent CCR9+CD4+ T cells are altered in secondary progressive multiple sclerosis.

The mechanism underlying the progression of relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS), characterized by accumulating fixed disability, is yet to be fully understood. Although alterations in the gut microbiota have recently been highlighted in multiple sclerosis pathogenesis, the mechanism linking the altered gut environment with the remote CNS pathology remains unclear. Here, we analyse human CD4+ memory T cells expressing the gut-homing chemokine receptor CCR9 and found a reduced frequency of CCR9+ memory T cells in the peripheral blood of patients with SPMS relative to healthy controls. The reduction in the proportion of CCR9+ cells among CD4+ memory T cells (%CCR9) in SPMS did not correlate with age, disease duration or expanded disability status scale score, although %CCR9 decreased linearly with age in healthy controls. During the clinical relapse of both, relapsing-remitting multiple sclerosis and neuromyelitis optica, a high proportion of cells expressing the lymphocyte activating 3 gene (LAG3) was detected among CCR9+ memory T cells isolated from the CSF, similar to that observed for mouse regulatory intraepithelial lymphocytes. In healthy individuals, CCR9+ memory T cells expressed higher levels of CCR6, a CNS-homing chemokine receptor, and exhibited a regulatory profile characterized by both the expression of C-MAF and the production of IL-4 and IL-10. However, in CCR9+ memory T cells, the expression of RORγt was specifically upregulated, and the production of IL-17A and IFNγ was high in patients with SPMS, indicating a loss of regulatory function. The evaluation of other cytokines supported the finding that CCR9+ memory T cells acquire a more inflammatory profile in SPMS, reporting similar aspects to CCR9+ memory T cells of the elderly healthy controls. CCR9+ memory T cell frequency decreased in germ-free mice, whereas antibiotic treatment increased their number in specific pathogen-free conditions. Here, we also demonstrate that CCR9+ memory T cells preferentially infiltrate into the inflamed CNS resulting from the initial phase and that they express LAG3 in the late phase in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Antibiotic treatment reduced experimental autoimmune encephalomyelitis symptoms and was accompanied by an increase in CCR9+ memory T cells in the peripheral blood. Antibodies against mucosal vascular addressin cell adhesion molecule 1 (MADCAM1), which is capable of blocking cell migration to the gut, also ameliorated experimental autoimmune encephalomyelitis. Overall, we postulate that the alterations in CCR9+ memory T cells observed, caused by either the gut microbiota changes or ageing, may lead to the development of SPMS.

Lymphoproliferation Impairment and Oxidative Stress in Blood Cells from Early Parkinson’s Disease Patients

In Parkinson’s Disease (PD), the peripheral changes in the functional capacity and redox state of immune cells has been scarcely investigated, especially in the early PD stages. Aging is a risk factor for PD, and the age-related impairment of the immune system, based on a chronic-oxidative stress situation, is involved in the rate of aging. We analyzed several functions in isolated peripheral blood neutrophils and mononuclear cells from PD stage 2 patients, and compared the results to those in healthy elderly and adult controls. Several oxidative stress and damage parameters were studied in whole blood cells. The results showed an impairment of the lymphoproliferative response in stimulated conditions in the PD patients compared with age-matched controls, who also showed typical immunosenescence in comparison with adult individuals. Higher oxidative stress and damage were observed in whole blood cells from PD patients (lower glutathione peroxidase activity, and higher oxidized glutathione and malondialdehyde contents). Our results suggest an accelerated immunosenescence in PD stage 2, and that several of the parameters studied could be appropriate peripheral biomarkers in the early stages of PD.

The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery.

The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNIT's sensitivity to cognitive change after shunt surgery in patients with INPH. Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist. Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p < 0.01); executive functions (Stroop incongruent color and word test, p < 0.01); attention (2-choice reaction test, p < 0.01); psychomotor speed (Stroop congruent color and word test, p < 0.01); and manual dexterity (4-finger tapping, p < 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p < 0.001 for all tests). In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.Clinical trial registration no.: NCT01618500 (clinicaltrials.gov).

Histopathology of diffusion imaging abnormalities in cerebral amyloid angiopathy.

We sought to determine the underlying mechanism for altered white matter diffusion tensor imaging (DTI) measures at the histopathologic level in patients with cerebral amyloid angiopathy (CAA). Formalin-fixed intact hemispheres from 9 CAA cases and 2 elderly controls were scanned at 3-tesla MRI, including a diffusion-weighted sequence. DTI measures (i.e., fractional anisotropy [FA] and mean diffusivity [MD]) and histopathology measures were obtained from 2 tracts: the anterior thalamic radiation and inferior longitudinal fasciculus. FA was reduced in both tracts and MD was increased in cases with CAA compared to controls. Regional FA was significantly correlated with tissue rarefaction, myelin density, axonal density, and white matter microinfarcts. MD correlated significantly with tissue rarefaction, myelin density, and white matter microinfarcts, but not axonal density. FA and MD did not correlate with oligodendrocytes, astrocytes, or gliosis. Multivariate analysis revealed that tissue rarefaction (β = -0.32 ± 0.12, p = 0.009) and axonal density (β = 0.25 ± 0.12, p = 0.04) were both independently associated with FA, whereas myelin density was independently associated with MD (β = -0.32 ± 0.12, p = 0.013). Finally, we found an association between increased MD in the frontal white matter and CAA severity in the frontal cortex (p = 0.035). These results suggest that overall tissue loss, and in particular axonal and myelin loss, are major components underlying CAA-related alterations in DTI properties observed in living patients. The findings allow for a more mechanistic interpretation of DTI parameters in small vessel disease and for mechanism-based selection of candidate treatments to prevent vascular cognitive impairment.

Slower Reorientation of Trunk for Reactive Turning while Walking in Hemiparesis Stroke Patients

We examined the behavioral characteristics of reactive turning in hemiplegic stroke patients when they were informed of the turning direction just before turning was required at an unpredictable time. Eleven stroke patients and 20 healthy elderly control people were asked to initiate a turn as soon as a visual cue to inform them of the turning direction was activated unpredictably using a foot switch. Both the segmental reorientation and stepping type when turning 90° while walking were measured. The results indicated preserved segmental reorientation of the head and pelvis in stroke patients. Stroke patients showed delays in pelvic turning but not in head turning. Their delayed pelvic movement might be due to motor dysfunction and the time taken to ensure stability when deciding when to turn.