Spectrum Of Cognitive Impairment Research Articles

Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system

HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments that continue to affect approximately half of all HIV-positive individuals despite effective viral suppression through antiretroviral therapy (ART). White matter pathologies have persisted in the ART era, and the degree of white matter damage correlates with the degree of neurocognitive impairment in patients with HAND. The HIV protein Nef has been implicated in HAND pathogenesis, but its effect on white matter damage has not been well characterized. Here, utilizing in vivo, ex vivo, and in vitro methods, we demonstrate that Nef-containing extracellular vesicles (Nef EVs) disrupt myelin sheaths and inflict damage upon oligodendrocytes within the murine central nervous system. Intracranial injection of Nef EVs leads to reduced myelin basic protein (MBP) staining and a decreased number of CC1 + oligodendrocytes in the corpus callosum. Moreover, cerebellar slice cultures treated with Nef EVs exhibit diminished MBP expression and increased presence of unmyelinated axons. Primary mixed brain cultures and enriched oligodendrocyte precursor cell cultures exposed to Nef EVs display a decreased number of O4 + cells, indicative of oligodendrocyte impairment. These findings underscore the potential contribution of Nef EV-mediated damage to oligodendrocytes and myelin maintenance in the pathogenesis of HAND.

Functional neural networks stratify Parkinson's disease patients across the spectrum of cognitive impairment.

Cognitive impairment (CI) is a significant non-motor symptoms in Parkinson's disease (PD) that often precedes the emergence of motor symptoms by several years. Patients with PD hypothetically progress from stages without CI (PD-normal cognition [NC]) to stages with Mild CI (PD-MCI) and PD dementia (PDD). CI symptoms in PD are linked to different brain regions and neural pathways, in addition to being the result of dysfunctional subcortical regions. However, it is still unknown how functional dysregulation correlates to progression during the CI. Neuroimaging techniques hold promise in discriminating CI stages of PD and further contribute to the biomarker formation of CI in PD. In this study, we explore disparities in the clinical assessments and resting-state functional connectivity (FC) among three CI stages of PD. We enrolled 88 patients with PD and 26 healthy controls (HC) for a cross sectional clinical study and performed intra- and inter-network FC analysis in conjunction with comprehensive clinical cognitive assessment. Our findings underscore the significance of several neural networks, namely, the default mode network (DMN), frontoparietal network (FPN), dorsal attention network, and visual network (VN) and their inter-intra-network FC in differentiating between PD-MCI and PDD. Additionally, our results showed the importance of sensory motor network, VN, DMN, and salience network (SN) in the discriminating PD-NC from PDD. Finally, in comparison to HC, we found DMN, FPN, VN, and SN as pivotal networks for further differential diagnosis of CI stages of PD. We propose that resting-state networks (RSN) can be a discriminating factor in distinguishing the CI stages of PD and progressing from PD-NC to MCI or PDD. The integration of clinical and neuroimaging data may enhance the early detection of PD in clinical settings and potentially prevent the disease from advancing to more severe stages.

Caregivers of People With Mild Cognitive Impairment and Dementia: Characterizing Social and Psychological Outcomes.

Little is known about caregiving across the spectrum of cognitive impairment [mild cognitive impairment (MCI) to dementia] and how early life and sociocultural factors affect caregiver health. In this study, we characterized differences between caregivers of those with MCI versus those with dementia. A total of 158 caregivers were enrolled in this cross-sectional study, most of whom were dementia caregivers (65%). Caregivers completed questionnaires on depressive symptoms, self-rated health (SRH), perceived burden and stress, as well as psychosocial and demographic measures. Caregivers of those with MCI reported fewer depressive symptoms and lower stress and burden compared with dementia caregivers. In adjusted analyses caregivers with greater stress reported more depressive symptoms. For SRH, at lower stress levels, having a sibling die before age 18 (ie, early life adversity) was associated with poorer SRH; at higher stress levels, having early life adversity was associated with better SRH. At lower burden levels, more live births were associated with worse SRH; at higher burden levels, more live births were associated with better SRH. Early life factors are relevant for caregivers of those with cognitive impairment and targeted prevention and early intervention may be helpful in alleviating caregiver burden and stress.

Vascular risk factors are a major contributor to cognitive impairment and degenerative dementia in India

AbstractBackgroundThe burden of vascular contribution to cognitive impairment and dementia is high in low and middle‐income countries (LMIC) like India. It is crucial to determine burden of vascular contribution to dementia in India, to develop effective preventive and treatment strategies. The aim of the study was to determine the prevalence of vascular risk factors across the spectrum of cognitive impairment and dementia in a large dementia cohort in South India.MethodPatients with cognitive impairment and dementia from the dementia registries of two University referral hospitals in South India were included. All patients underwent clinical, cognitive and imaging study and standard criteria were used to diagnose MCI, AD, FTD, VaD and mixed dementia. Vascular risk factor profile was determined in patients, and the presence of hypertension, diabetes, cardiac disease, stroke, smoking and chronic alcoholism were noted.ResultOf a total 1811 patients with cognitive impairment, 180 (9.9%) patients were diagnosed to have MCI, 517 (28.5%) AD, 205 (11.3%) FTD, 844 (46.6%) had VaD & 64 (3.5%) had mixed dementia. Overall, hypertension was the most prevalent vascular risk factor (62.7%) followed by stroke (46.6%). 35.5% of patients had diabetes mellitus(DM), 15.2% had chronic alcoholism, 14.4% were smokers and 14.2% had history of cardiac disorders.Hypertension was most commonly encountered in patients with AD (76.4%), followed by mixed Dementia (68.75%), VaD (63.4%), MCI (44.4%) and FTD (39.5%).DM was present in a high proportion of all subtypes of cognitive impairment and dementia (24.4% to 46.8%). The proportion of patients with stroke was highest in VaD (82.1%), but was also associated with one‐fourth of patients with AD and 15% of patients with mixed dementia. Frequency of smoking, chronic alcoholism and cardiac disease was highest in mixed dementia and VaD.ConclusionOur results demonstrate that a large burden of vascular risk factors exist in all forms of cognitive impairment and dementia in the Indian context. Hypertension and diabetes were found to be commonly associated with neurodegenerative dementia, in addition to vascular and mixed dementia. This large burden of vascular contribution represents needs and an opportunity to implement strategies to reduce burden of dementia in India and other LMICs

P012 Head Position During Sleep: Potential Implications for Patients with Neurodegenerative Disorders

Abstract Introduction In 2015, Lee et al. observed sleeping position influenced the efficiency of glymphatic clearance in rats. In 2018, Levendowski et al. reported supine sleep was independently associated with neurodegenerative disorders (NDD)(odds ratio=3.7). This update further evaluates the comparative frequency of the supine sleep position across a spectrum of cognitive impairment, including patients diagnosed with a Parkinsonian spectrum disorder (PSD), Alzheimer’s disease dementia (AD) and mild cognitive impairment (MCI), compared with a control group (CG) of patients without a known cognitive disorder. Methods After ethics review and with informed consent, a control group (CG: n=170), PSD (n=36), AD (n=29) and MCI group (n=41) were studied in-home with the Sleep Profiler; 89% across two-nights. Between-group comparisons were assessed with Mann-Whitney U and Chi-square tests. Results The hours of supine sleep were greater in PSD=3.0 + 1.9, AD=3.2 + 2.0 and MCI=3.0 + 2.0 vs. CG=1.9 + 1.8 (all p<0.002). The proportion of patients with >2 hours of supine sleep were PSD=69%, AD=69% and MCI=59% vs. CG=39%, with odds ratios of PSD=3.6, AD=3.5 and MCI=2.2 (all p<0.001). Conclusions Here we provide further evidence for a relatively strong association between supine sleep and neurodegenerative disease including PSD, AD and MCI cohorts. The nature of this association remains unclear from cross sectional study designs. Future prospective studies should test if there is a causal link between supine sleep and subsequent development of neurodegeneration.

Role of Citicoline in Patients With Mild Cognitive Impairment.

The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders. Citicoline is a pharmaceutical product constituted by the combination of 2 natural molecules (cytidine and choline) and is marketed as a food supplement. It has been proposed to provide neuroprotective effects through diverse mechanisms of action. Taking into account the available literature, citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin. Moreover, it provides beneficial effects on vascular, Alzheimer, and mixed dementias, stroke sequelae, intracerebral hemorrhages, traumatic brain injuries, and neurodegenerative diseases. Long-term treatment with citicoline has also been demonstrated to be well-tolerated and has not been associated with severe adverse events. Citicoline is a safe, well-tolerated, and promising agent with evidenced neuroprotective properties.

Cognitive change in frail individuals with intermediate amyloid load: Insight from the MAPT interventional study (+ Running poster)

In the past decade, in vivo cerebral amyloid load in the spectrum of cognitive impairment has been extensively explored using positron emission tomography (PET), and is now a key part of screening visits for most therapeutic studies. However, to date, little if no distinction is made between patients with low to medium amyloid load versus patients with high amyloid load, in terms of both the risk of developing AD and the progression of cognitive change. Here, we investigated the cognitive changes in frail participants to a multidomain interventional study (Andrieu et al., Lancet 2017), according to the degree of cerebral amyloid load: absent/low, medium, high. Two hundred and forty five participants to the MAPT study were selected. All of them underwent a full cognitive assessment, and were follow-up for up to five years. They all underwent a cerebral amyloid PET scan using [18F]florbetapir. All of them had been randomized at the beginning of the trial into one of four intervention groups: multidomain intervention and daily omega-3 intake; multidomain intervention and placebo; omega-3 uptake alone; the placebo alone. Cortical amyloid load was quantified from PET imaging as the mean standard uptake value ratio in all regions of the brain (parcelated according to the AAL atlas; cerebellar grey matter as reference). Patients were categorized into “low”, “medium”, or “high” cerebral amyloid using k-clustering. Cognitive functions were measured as a composite score combining four tests. Using a linear regression model, we investigated how cognition progressed over time according to amyloid status and the intervention group. Our findings were two-fold: patients in the “high amyloid” group showed cognitive decline over time, while patients in the “medium amyloid” group exhibited a cognitive profile stable and similar to the patients with “low amyloid” load ( P < 0.001). In addition, in the “medium amyloid” group only, we observed an improvement of cognitive performance over time for patients of all intervention group, except for patients in the placebo group (i.e., without intervention at all), who showed stable cognitive performance ( P < 0.05). Our findings suggest that having a moderate or high amyloid load is not equivalent in terms of impact on cognitive progression in the short-term (5 years), and that patients with moderate rather than high amyloid load may be a better suited target for drug studies.

Disappearing metabolic youthfulness in the cognitively impaired female brain

Sex differences play a vital role in human brain structure and physiology. Previous reports have proposed evidence hinting at a metabolic advantage in female brains across adulthood. It remained to be determined whether this advantage would be maintained across the spectrum of cognitive impairment, up to and including dementia due to Alzheimer's disease (AD). Here, using a machine-learning algorithm, we explore sex differences in metabolic brain-age derived from fluorodeoxyglucose positron emission tomography imaging among cognitively healthy individuals and those affected by mild cognitive impairment and clinically probable AD. First, we report that cognitively healthy male participants showed a persistently “older” looking brains when compared to healthy female participants in term of metabolic brain age, confirming earlier reports. However, this distinction disappeared among MCI individuals and probable AD patients, and this loss could not be explained by an accompanying neurodegeneration. This would seem to indicate that females have a higher rate of decline in brain glucose metabolism when cognitively impaired to negate their prior advantage.

Relationship Between Patient and Informant Assessment of Personality and Cognitive Status

Personality has been linked to risk of dementia. Most studies ask individuals to rate their own personality traits or for a knowledgeable informant to perform the rating; few collect data from both. When informants are asked to give an estimate of the patient’s lifelong personality traits, they often describe personality before disease onset. When asked to self-rate, patients may instead assess their personality as they see themselves, providing a personality-state measure. The goal of this study was to assess agreement between two independent measures of personality and evaluate whether stage of cognitive impairment and characteristics of patients or caregivers impact concordance. In 79 consecutive patient-caregiver dyads presenting to our center (mean age:76.8±8.4; 44.1% female; 6% cognitively normal, 41% MCI; and 53% dementia) with in-depth psychosocial and neuropsychological evaluations, we found informants rated patients lower on openness (O) (ICC=0.434; 95%CI: 0.235-0.598) and agreeableness (A) (ICC=0.491; 95%CI: 0.302-0.643) and higher on extraversion (O) (ICC=0.396; 95%CI: 0.191-0.568) and neuroticism (N) (ICC=0.444; 95%CI: 0.247-0.607). Greater discordance was observed in established dementia (ICCE=0.497; 95%CI: 0.222-0.700; ICCA=0.337; 95%CI:0.031-0.586; ICCN=0.422; 95%CI: 0.191-0.683), compared with MCI (ICCO=0.568; 95%CI: 0.282-0.762). We explored the effect of patient and caregiver mood and caregiver burden on personality ratings. Although personality is typically described as a trait, we present evidence that in the eyes of patients, personality ratings may represent a state that changes across the spectrum of cognitive impairment. Understanding how patients and caregivers differentially perceive personality may assist in developing novel psychotherapeutic interventions and approaches dealing with behavioral manifestations of dementia.

Neuropsychiatric correlates of cerebral amyloid burden in a memory clinic sample

AbstractBackgroundNeuropsychiatric symptoms (NPS) affect quality of life for both patients and caregivers, worsen cognitive and functional impairment in elderly, and are associated with the development of dementia. Manifestations of neurodegenerative and vascular pathologies including abnormal amyloid deposition and cerebrovascular disease (CeVD) often co‐exist in both cognitively normal and impaired elderly. However, the impact of co‐occurrence of amyloid and CeVD on major clinical outcomes, such as neurocognition and neuropsychiatric disorders, have not been extensively explored. Hence, the present study aimed to determine the neuropsychiatric correlates of cerebral amyloid burden amongst patients across a spectrum of cognitive impairment, adjusting for significant CeVD. We hypothesized that amyloid burden is independently associated with NPS severity.MethodParticipants with or without cognitive impairment from the memory clinic underwent [11C]PiB‐PET and MRI scans between April 2016 and September 2018. NPS were assessed using the 12‐item neuropsychiatric inventory. CeVD markers (cortical infarcts, stenosis, white matter hyperintensities, lacunes, and microbleeds) were graded and significant CeVD was defined following previously validated criteria. The association of NPS severity with global standardized uptake value ratio (SUVR) was analyzed using generalized linear models, controlling for demographics, diagnosis, cognitive function, depression status, and significant CeVD. Possible interactions between amyloid and CeVD were evaluated. The correlations between NPS subsyndromes and regional amyloid uptake were also explored. Holm‐Bonferroni correction was applied to adjust for multiple comparisons.ResultsData for 168 participants [age=75.6 (7.3); female=93 (55.4%); MMSE=22.3 (5.7)] were analyzed, including 24 cognitively normal, 89 MCI, and 55 with dementia. Global SUVR was associated with higher total NPS score [β (CI)=0.67 (0.15‐1.18), p=0.011], driven by hyperactivity subsyndrome [β (CI)=0.96 (0.15‐1.11), p=0.002] and apathy subsyndrome [β (CI)=0.90 (0.34‐1.45), p=0.002]. Apathy subsyndrome was positively correlated with amyloid uptake in the thalamus (r=0.25, p=0.002) and parietal region (r=0.224, p=0.002). There was no significant interaction between global SUVR and significant CeVD on NPS.ConclusionNeuropsychiatric manifestations reflect underlying neurodegenerative pathology independent of vascular burden, suggesting that amyloid and CeVD may exert their effects through different pathways. This finding contributes to the neuropathological understanding of neuropsychiatric disorders, thus informs future development of novel treatment and monitoring of disease progression.

The association of peripheral immune markers with brain cortical thickness and surface area in South African people living with HIV.

A spectrum of cognitive impairments known as HIV-associated neurocognitive disorders (HAND) are consequences of the effects of HIV-1 within the central nervous system. Regardless of treatment status, an aberrant chronic neuro-immune regulation is a crucial contributor to the development of HAND. However, the extent to which inflammation affects brain structures critical for cognitive status remains unclear. The present study aimed to determine associations of peripheral immune markers with cortical thickness and surface area. Participants included 65 treatment-naïve HIV-positive individuals and 26 HIV-negative controls. Thickness and surface area of all cortical regions were derived using automated parcellation of T1-weighted images acquired at 3T. Peripheral immune markers included C-C motif ligand 2 (CCL2), matrix metalloproteinase 9 (MMP9), neutrophil gelatinase-associated lipocalin (NGAL), thymidine phosphorylase (TYMP), transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF), which were measured using enzyme-linked immunosorbent assays. Associations of these markers with thickness and surface area of cortical regions were evaluated. A mediation analysis examined whether associations of inflammatory markers with cognitive functioning were mediated by brain cortical thickness and surface area. After controlling for multiple comparisons, higher NGAL was associated with reduced thickness of the bilateral orbitofrontal cortex in HIV-positive participants. The association of NGAL with worse motor function was mediated by cortical thickness of the bilateral orbitofrontal region. Taken together, this study suggests that NGAL plays a potential role in the neuropathophysiology of neurocognitive impairments of HIV.

Global cerebrovascular burden and long-term clinical outcomes in Asian elderly across the spectrum of cognitive impairment.

A case-control study was conducted over a 2-year period involving participants with no cognitive impairment, cognitive impairment-no dementia (CIND), and Alzheimer's disease (AD). Annually, cognitive function was assessed with a comprehensive neuropsychological battery and the clinical dementia rating (CDR) scale was used to stage disease severity. Of 314 participants, 102 had none/very mild CeVD, 31 mild CeVD, 94 moderate CeVD, and 87 severe CeVD at baseline. There was a 1.14 and 1.42 units decline per year on global cognitive z-scores in moderate and severe CeVD groups, respectively, compared to none/very mild CeVD. Moderate-severe CeVD predicted significant functional deterioration at year 2 (HR = 2.0, 95% CI = 1.2-3.4), and conversion to AD (HR = 6.3, 95% CI = 1.7-22.5), independent of medial temporal atrophy. The global CeVD burden scale predicts poor long-term clinical outcome independent of neurodegenerative markers. Furthermore, CeVD severity affects the rate of cognitive and functional deterioration. Hence, cerebrovascular burden, which is potentially preventable, is a strong prognostic indicator, both at preclinical and clinical stages of AD, independent of neurodegenerative processes.

Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.

BackgroundVascular cognitive impairment (VCI) is a spectrum of cognitive impairment caused by various chronic diseases including aging, hypertension, and diabetes mellitus. Oxidative and inflammatory reactions induced by chronic cerebral hypoperfusion (CHP) are believed to cause VCI. Melatonin is reported to possess anti-oxidation and anti-inflammation effects. This study was designed to investigate the effect and mechanisms of melatonin in CHP mice model.ResultsThe behavioral function results revealed that CHP mice were significantly impaired when compared with the control. Melatonin improved the cognitive function, but the addition of MT2 receptor antagonist reversed the improvement. The IHC staining showed melatonin significantly improved WM lesions and gliosis in CHP mice. Again, the addition of MT2 receptor antagonist to melatonin worsened the WM lesion and gliosis. Similar results were also found for mRNA and protein expressions of oxidative reaction and inflammatory cytokines.Materials and MethodForty C57BL/6 mice were divided into four groups: Group 1: sham control; Group 2: CHP mice; Group 3: CHP with melatonin treatment; Group 4: CHP-melatonin and MT2 receptor antagonist (all groups n = 10). Working memory was assessed with Y–arm test at day-28 post-BCAS (bilateral carotid artery stenosis). All mice were sacrificed at day-30 post-BCAS. The immunohistochemical (IHC) staining was used for white matter (WM) damage and gliosis. The expression of mRNA and proteins about inflammatory and oxidative reaction were measured and compared between groups.ConclusionsPartially through MT2 receptor, melatonin is effective for CHP-induced brain damage.

Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia.

Vascular pathology plays an important role in the development of cognitive decline and dementia. In this context, growth differentiation factor-15 (GDF-15) has been suggested to be a biomarker due to its regulatory roles in inflammatory and trophic responses during tissue injury. However, limited data exist on the associations of GDF-15 with either cerebrovascular disease (CeVD) burden or the spectrum of cognitive impairment. Therefore, we aimed to study peripheral levels of GDF-15 incognitive impairment no dementia (CIND) or Alzheimer disease (AD) subjects assessed for CeVD using a case-control cohort design, with cases recruited from memory clinics and controls from memory clinics and the community. All subjects underwent detailed neuropsychological assessment, 3-Tesla magnetic resonance imaging, and venous blood draw. Subjects were classified as CIND or AD based on clinical criteria, while significant CeVD was defined as the presence of cortical infarcts and/or 2 lacunes or more, and/or confluent white matter hyperintensities (WMHs) in 2 or more brain regions. A total of 324 subjects were included in the study, of whom 80 had no cognitive impairment, 144 CIND and 100with AD. Higher GDF-15 levels were significantly associated with disease groups, especially in the presence of CeVD, namely, CIND with CeVD (odds ratios [OR]: 7.21; 95% confidence interval [CI]: 2.14-24.27) and AD with CeVD (OR: 21.87; 95% CI: 2.01-237.43). Among the different CeVD markers, only WMH was associated with higher GDF-15 levels (OR: 3.97; 95% CI: 1.79-8.83). The associations between GDF-15 and cognitive impairment as well as with WMH remained significant after excluding subjects with cardiovascular diseases. In conclusion, we showed that increased GDF-15 may be a biomarker for CIND and AD in subjects with WMH.

Cognitive impairment in idiopathic Parkinson's disease.

Cognitive symptoms are common in advanced Parkinson's disease (PD). However, assessment of cognitive impairment is difficult in PD because of accompanying motor symptoms and the coexistence of nonmotor symptoms. Specific subdomains affected in the disease are not reflected in the conventional scales used for assessing cognition. This study was aimed at looking at the spectrum of cognitive impairment in the various phenotypes and stages of PD and the correlation of cognitive impairment with motor and nonmotor symptoms of PD. Fifty PD patients fulfilling the UK PD Society Brain Bank's criteria were selected after obtaining explicit consent. Patients were assessed clinically and by using various scales like Scales for Outcomes in PD-Cognition (SCOPA-COG), mini-mental state examination, and Beck's Depression Inventory and Scoring. The mean age was 58 years, 82% of the patients were male, and the mean modified Hoehn and Yahr staging was 2. The most commonly affected domains were memory and executive functioning. Cognitive impairment was more in those with late-onset disease, more advanced stage of disease, and in the postural instability and gait disorder (PIGD) subgroup. The cognitive function deteriorated with increasing age and duration of the illness. Significant correlation with cognitive impairment was obtained for the manifestations of increased motor disability, presence of coexistent psychotic symptoms and depression. Cognitive impairment was common among PD patients, and it was more prevalent with increasing duration of the disease, in older patients, in late-onset disease, and in the PIGD subgroup. Increasing motor disability and associated psychotic symptoms as well as depression significantly increased the cognitive impairment.

Covert and Overt Hepatic Encephalopathy: Current Options for Diagnosis and Treatment

Overt hepatic encephalopathy (OHE) and covert hepatic encephalopathy (CHE) are two clinically distinct entities that are at the end of the spectrum of cognitive impairment due to portal hypertension. They are fraught with diagnostic and treatment challenges, but both could result in serious complications if not intervened upon in a timely fashion. CHE has been recognized as a harbinger to OHE providing an opportunity to intervene. There are numerous diagnostic strategies for CHE, and most require specialized equipment, trained personnel, and time. Diagnosis of OHE is significantly easier compared to CHE. As such, the psychometric tests have been more favored due to less dependence on specialized equipment and personnel, and their ability to be equally reliable compared to neuropsychological tests. While we have learned more about the pathophysiology of hepatic encephalopathy, our treatment modalities have not evolved as much. A collaborative approach to management, with development of easier reliable tests, will help us combat this epidemic.

Abstract W P80: Predictors of Cognitive Status in Post-Aneurysm Surgery Patients

Introduction: Patients who undergo surgical treatment for ruptured intracranial aneurysms may have a different risk profile for a spectrum of cognitive impairment based upon characteristics at presentation of their subarachnoid hemorrhage. Methods: The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) is a multi-center, prospective, randomized clinical trial investigation of whether induced hypothermia during surgical treatment for subarachnoid hemorrhage resulted in improved outcomes. Cognitive status was defined by raw Mini-Mental Status Examination (MMSE) cutoff scores. A normal cognition was defined as a MMSE score of 28 or greater. Mildly impaired patients were defined as a score of 24-27, and severely impaired patients were defined as those with a score of less than 24. Age was analyzed by five-year age groups, with the exception of patients 30 or younger and patients 75 and older. Ordinal logistic regression was utilized to determine the final predictors. Results: Of the 1,000 patients who were followed for cognitive testing, 61 died and 21 were medically untestable. Five patients refused testing and tests were not administered to 30 patients. A total of 883 patients completed the MMSE at 3 months post-surgery. Based on the raw MMSE scores, the median score for the severely impaired patients was 20 (IQR: 16-22), 26 (IQR: 25-27) for mildly impaired patients, and 29 (IQR: 29-30) for cognitively normal patients. Gender, and race were found to be statistically significant (p&lt;.05) predictors after controlling for age and education. Baseline Rankin Score and the occurrence of a leakage or rupture during surgery were also predictive of cognitive status. The World Federation of Neurosurgical Societies Score, the Fisher’s SAH Score, and aneurysm size and location were not found to be statistically significant. Conclusion: Patients with surgical treatment for subarachnoid hemorrhage share several demographic risk factors associated with cognitive changes in the general public, but have additional neurological risk factors associated with SAH and aneurysm procedures.

Apathy is not associated with performance in brief executive tests in patients with mild cognitive impairment and mild Alzheimer's disease.

Neuropsychological correlates of apathy in Alzheimer's disease (AD) may shed some light on the neurobiology of this behavioral disorder. Whereas previous research has suggested an association between apathy and executive functions in AD, amnestic mild cognitive impairment (aMCI) cohorts point to an association with memory tests. We aimed to further investigate this issue in a sample of low educated, hitherto unexposed to cholinesterase inhibitors, aMCI (n=26) and mild AD (n=28) patients using brief executive tests, namely the Executive Interview (EXIT-25) and the Frontal Assessment Battery (FAB). Patients and controls (n=33) were included from a community-based survey of successful brain aging in Brazilian elderly (75+ years), The Pietà Study. The participants were submitted to a comprehensively neuropsychological assessment and apathy evaluation through the Apathy Scale (AS).We found a strong correlation in AD group between AS scores and functional performance measured by the Disability Assessment in Dementia (rho =-0.7 ; p<0,001). No association was found between any executive test performance and apathy symptoms. Apathy symptoms were also associated with the performance in memory tests and in the attention subscale of the Mattis Dementia Rating Scale. These findings reinforce the functional effect of apathy even in the mildest stages along the AD cognitive impairment spectrum, and challenges previous assumptions regarding the association between apathy and classical executive functions.

The spectrum of cognitive impairment in Lewy body diseases.

Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson's disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. It is now recognized that cognitive dysfunction occurs not only in more advanced Parkinson's disease but also in early, untreated patients and even in those patients with pre-motor syndromes, such as rapid eye movement behavior disorder and hyposmia. In recent years, the concept of mild cognitive impairment as a transitional or pre-dementia state in Parkinson's disease has emerged. This has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson's disease, but has also raised questions regarding the usefulness of this concept and its application in clinical and research settings. In addition, the conundrum of whether Parkinson's disease dementia and dementia with Lewy bodies represent the same or different entities remains unresolved. Although these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other elements, such as timing of cognitive, behavioral, and motor symptoms; medication responses; and neuropathological contributions. This article examines the spectrum and evolution of cognitive impairment in Lewy body disorders and debates these controversial issues in the field using point-counterpoint approaches.

Spectrum of Cognitive Impairment in Korean ALS Patients without Known Genetic Mutations

BackgroundCognitive impairment is associated with a negative prognosis in amyotrophic lateral sclerosis (ALS), as well as with clinical specificity. We investigate neuropsychological function in ALS patients without known genetic mutations in a Korean tertiary clinic.MethodsThree hundred and eighteen patients were enrolled in a prospective longitudinal cohort from September 2008 to February 2012. At the time of diagnosis of sporadic ALS, we carried out genetic and comprehensive neuropsychological tests on all patients, and collected demographic and clinical characteristics. Six cognitive domains, namely executive function, attention, language, calculation, visuospatial function and memory were evaluated. ANOVA and t-tests were used to assess differences in clinical characteristics and neuropsychological parameters between sporadic ALS patients. The Kaplan-Meier method and Cox proportional hazard model were used for survival analysis.ResultsOne hundred and sixty-six patients were categorized into five subtypes: normal cognition (ALS pure), cognitive impairment (ALSci), behavioral impairment (ALSbi), frontotemporal dementia (ALS-FTD), and other types of dementia. Seventy patients (70/166, 42.2%) were cognitively or behaviorally impaired. Among the impaired patients, eight (8/166, 4.8%) had FTD-type dementia and one (1/166, 0.6%) was Alzheimer's disease-type. The ALS patients with cognitive impairment (ALSci) and with FTD (ALS-FTD) were more severely impaired in executive function, attention, language and memory than the cognitively intact ALS patients (ALS pure). In a survival analysis, ALSci (β = 1.925, p = 0.025) and ALS-FTD groups (β = 4.150, p = 0.019) tended to have shorter survival than the ALS pure group.ConclusionsAbout half of ALS patients without known genetic variation have cognitive or behavioral impairment. ALS patients with cognitive abnormalities, especially FTD, have a poorer prognosis than those without cognitive impairment. In neuropsychological profiling, executive tasks were effective in identifying cognitive impairment in the ALS patients. It would be useful for clinicians to classify ALS according to neuropsychological profiles, and screen for subtle cognitive impairment.