Structural brain networks correlating with poststroke cognition.

Cognitive deficits are a common and debilitating consequence of stroke, yet our understanding of the structural neurobiological biomarkers predicting recovery of cognition after stroke remains limited. In this longitudinal observational study, we set out to investigate the effect of both focal lesions and structural connectivity on poststroke cognition. Sixty-two patients with stroke underwent advanced brain imaging and cognitive assessment, utilizing the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), at 3-month and 12-month poststroke. We first evaluated the relationship between lesions and cognition at 3 months using voxel-based lesion-symptom mapping. Next, a novel correlational tractography approach, using multi-shell diffusion-weighted magnetic resonance imaging (MRI) data collected at both time points, was used to evaluate the relationship between the white matter connectome and cognition cross-sectionally at 3 months, and longitudinally (12 minus 3 months). Lesion-symptom mapping did not yield significant findings. In turn, correlational tractography analyses revealed positive associations between both MoCA and MMSE scores and bilateral cingulum and the corpus callosum, both cross-sectionally at the 3-month stage, and longitudinally. These results demonstrate that rather than focal neural structures, a consistent structural connectome underpins the performance of two frequently used cognitive screening tools, the MoCA and the MMSE, in people after stroke. This finding should encourage clinicians and researchers to not only suspect cognitive decline when lesions affect these tracts, but also to refine their investigation of novel approaches to differentially diagnosing pathology associated with cognitive decline, regardless of the aetiology.

Italian reference values and brain correlates of verbal fluency index - vs standard verbal fluency test - to assess executive dysfunction in ALS.

Objectives: In amyotrophic lateral sclerosis (ALS), verbal fluency index (Vfi) is used to investigate fluency accounting for motor impairment. This study has three aims: (1) to provide Vfi reference values from a cohort of Italian healthy subjects; (2) to assess the ability of Vfi reference values (vs standard verbal fluency test [VFT]) in distinguishing ALS patients with and without executive dysfunction; and (3) to investigate the association between Vfi and brain structural features of ALS patients. Methods: We included 180 healthy subjects and 157 ALS patients who underwent neuropsychological assessment, including VFT and Vfi, and brain MRI. Healthy subjects were split into four subgroups according to sex and education. For each subgroup, we defined the 95th percentile of Vfi as the cutoff. In ALS, the distributions of "abnormal" cases based on Vfi and standard VFT cutoffs were compared using Fisher's exact test. Using quantile regressions in patients, we assessed the association between Vfi and VFT scores, separately, with gray matter volumes and white matter (WM) tract integrity. Results: Applying Vfi and VFT cutoffs, 9 and 13% of ALS cases, respectively, had abnormal scores (p < 0.001). In ALS, while higher Vfi scores were associated with WM changes of callosal fibers linking supplementary motor area, lower VFT performances related to corticospinal tract alterations. Discussion: We provided Italian reference values for the spoken Vfi. Compared to VFT, Vfis are critical to disentangle motor and cognitive deficits in ALS. In patients, abnormal Vfis were associated with damage to WM tracts specifically involved in ideational information processing.

Neuropsychiatric Manifestations of Wilson Disease: Correlation with MRI and Glutamate Excitotoxicity.

This study aims to identify neuropsychiatric manifestations in neurological Wilson disease (NWD), and their correlation with MRI changes and glutamate excitotoxicity. Forty-three consecutive patients with NWD from a tertiary care teaching hospital were evaluated prospectively who fulfilled the inclusion criteria. The neuropsychiatric evaluation was done using Neuropsychiatric Inventory (NPI) battery that assesses 12 domains including delusion, hallucination, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, appetite change, and abnormal nighttime behavior. Cranial MRI was done using a 3 T machine, and locations of signal changes were noted including the total number of MRI lesions. Serum glutamate level was measured by a fluorescence microplate reader. Abnormal NPI in various domains and total NPI scores were correlated with MRI lesions, serum and urinary copper, and glutamate level. The median age of the patients was 16 years. Forty-one (48.8%) patients had cognitive impairment and 37 (86%) had movement disorder. Neurobehavioral abnormality was detected in all-commonest being agitation (90.7%) followed by appetite change (81.4%), elation (74.4%), irritability (69.8%), anxiety (67.4%), depression (65.1%), apathy (44.2%), night time abnormal behavior (32.6%), aberrant motor behavior (20.9%), delusions (16.3%), and hallucination (18.6%). The thalamic lesion was associated with depression, globus pallidus with depression and anxiety, caudate with anxiety and agitation, brainstem with irritability, and frontal cortex with apathy. Serum glutamate level was higher in NWD. NPI sum score correlated with MRI load and glutamate level. Varying severity of neurobehavioral abnormalities are common in the patients with NWD and correlate with the location of MRI lesion and glutamate level.

Cognitive Functions in Adult-Onset Phenotypes of X-Linked Adrenoleukodystrophy.

OBJECTIVE: X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder characterized by progressive demyelination ranging from mild myelopathic forms (adrenomyeloneuropathy [AMN]) to severe cerebral variants (adult cerebral adrenoleukodystrophy [ACALD]). The aim of this study was to compare cognitive function in adult-onset X-ALD phenotypes. METHODS: Cognitive function in various domains (intelligence, attention, memory, executive function, and processing speed) was assessed in 172 adults (117 with AMN, 30 with arrested ACALD, and 25 with acute ACALD) using comprehensive neuropsychological batteries. Phenotype differences were examined by analyses of variance. RESULTS: X-ALD phenotypes significantly differed in nonverbal intelligence, sustained attention, verbal encoding, nonverbal recognition, and processing speed (ps < 0.050). No group differences emerged regarding verbal intelligence, verbal retrieval and recognition, and executive function (ps > 0.050). Specifically, patients with acute ACALD showed severe cognitive deficits compared to AMN and normal data, with largest effects on processing speed. Contrary, cognition was overall intact in patients with AMN, independent of sex and corticospinal tract involvement, and those with arrested ACALD showed mild cognitive dysfunction, particularly in verbal encoding and processing speed. INTERPRETATION: Cerebral demyelination in patients with X-ALD causes white matter dementia, mainly characterized by an extreme slowdown in processing speed associated with deficits in attention and learning. Most patients with AMN show intact cognitive function. Future prospective, longitudinal studies with more sensitive imaging techniques are required to clarify whether early mild cognitive dysfunction found in some patients with AMN may be associated with subtle myelin abnormalities that do not yet appear as white matter lesions on cerebral MRI (cMRI) but have the potential to serve as early predictors of later cerebral progression. ANN NEUROL 2021;90:266-273.

Prediction of Cognitive Recovery After Stroke: The Value of Diffusion-Weighted Imaging-Based Measures of Brain Connectivity.

BACKGROUND AND PURPOSE: Prediction of long-term recovery of a poststroke cognitive disorder (PSCD) is currently inaccurate. We assessed whether diffusion-weighted imaging (DWI)-based measures of brain connectivity predict cognitive recovery 1 year after stroke in patients with PSCD in addition to conventional clinical, neuropsychological, and imaging variables. METHODS: This prospective monocenter cohort study included 217 consecutive patients with a clinical diagnosis of ischemic stroke, aged ≥50 years, and Montreal Cognitive Assessment score below 26 during hospitalization. Five weeks after stroke, patients underwent DWI magnetic resonance imaging. Neuropsychological assessment was performed 5 weeks and 1 year after stroke and was used to classify PSCD as absent, modest, or marked. Cognitive recovery was operationalized as a shift to a better PSCD category over time. We evaluated 4 DWI-based measures of brain connectivity: global network efficiency and mean connectivity strength, both weighted for mean diffusivity and fractional anisotropy. Conventional predictors were age, sex, level of education, clinical stroke characteristics, neuropsychological variables, and magnetic resonance imaging findings (eg, infarct size). DWI-based measures of brain connectivity were added to a multivariable model to assess additive predictive value. RESULTS: Of 135 patients (mean age, 71 years; 95 men [70%]) with PSCD 5 weeks after ischemic stroke, 41 (30%) showed cognitive recovery. Three of 4 brain connectivity measures met the predefined threshold of P<0.1 in univariable regression analysis. There was no added value of these measures to a multivariable model that included level of education and infarct size as significant predictors of cognitive recovery. CONCLUSIONS: Current DWI-based measures of brain connectivity appear to predict recovery of PSCD but at present have no added value over conventional predictors.

Predicting disability progression and cognitive worsening in multiple sclerosis using patterns of grey matter volumes.

OBJECTIVE: In multiple sclerosis (MS), MRI measures at the whole brain or regional level are only modestly associated with disability, while network-based measures are emerging as promising prognostic markers. We sought to demonstrate whether data-driven patterns of covarying regional grey matter (GM) volumes predict future disability in secondary progressive MS (SPMS). METHODS: We used cross-sectional structural MRI, and baseline and longitudinal data of Expanded Disability Status Scale, Nine-Hole Peg Test (9HPT) and Symbol Digit Modalities Test (SDMT), from a clinical trial in 988 people with SPMS. We processed T1-weighted scans to obtain GM probability maps and applied spatial independent component analysis (ICA). We repeated ICA on 400 healthy controls. We used survival models to determine whether baseline patterns of covarying GM volume measures predict cognitive and motor worsening. RESULTS: We identified 15 patterns of regionally covarying GM features. Compared with whole brain GM, deep GM and lesion volumes, some ICA components correlated more closely with clinical outcomes. A mainly basal ganglia component had the highest correlations at baseline with the SDMT and was associated with cognitive worsening (HR=1.29, 95% CI 1.09 to 1.52, p<0.005). Two ICA components were associated with 9HPT worsening (HR=1.30, 95% CI 1.06 to 1.60, p<0.01 and HR=1.21, 95% CI 1.01 to 1.45, p<0.05). ICA measures could better predict SDMT and 9HPT worsening (C-index=0.69-0.71) compared with models including only whole and regional MRI measures (C-index=0.65-0.69, p value for all comparison <0.05). CONCLUSIONS: The disability progression was better predicted by some of the covarying GM regions patterns, than by single regional or whole-brain measures. ICA, which may represent structural brain networks, can be applied to clinical trials and may play a role in stratifying participants who have the most potential to show a treatment effect.

White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling.

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.

Acute Imaging Findings Predict Recovery of Cognitive and Motor Function after Inpatient Rehabilitation for Pediatric Traumatic Brain Injury: A Pediatric Brain Injury Consortium Study.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children; survivors experience long-term cognitive and motor deficits. To date, studies predicting outcome following pediatric TBI have primarily focused on acute behavioral responses and proxy measures of injury severity; unsurprisingly, these measures explain very little of the variance following heterogenous injury. In adults, certain acute imaging biomarkers help predict cognitive and motor recovery following moderate to severe TBI. This multi-center, retrospective study, characterizes the day-of-injury computed tomographic (CT) reports of pediatric, adolescent, and young adult patients (2 months to 21 years old) who received inpatient rehabilitation services for TBI (n = 247). The study also determines the prognostic utility of CT findings for cognitive and motor outcomes assessed by the Pediatric Functional Independence Measure, converted to age-appropriate developmental functional quotient (DFQ), at discharge from rehabilitation. Subdural hematomas (66%), contusions (63%), and subarachnoid hemorrhages (59%) were the most common lesions; the majority of subjects had less severe Rotterdam CT scores (88%, ≤ 3). After controlling for age, gender, mechanism of injury, length of acute hospital stay, and admission DFQ in multivariate regression analyses, the highest Rotterdam score (ß = -25.2, p < 0.01) and complete cisternal effacement (ß = -19.4, p < 0.05) were associated with lower motor DFQ, and intraventricular hemorrhage was associated with lower motor (ß = -3.7, p < 0.05) and cognitive DFQ (ß = -4.9, p < 0.05). These results suggest that direct detection of intracranial injury provides valuable information to aid in prediction of recovery after pediatric TBI, and needs to be accounted for in future studies of prognosis and intervention.

Categorising a problem: alcohol and dementia.

Alcoholism is a chronic relapsing disorder that can include extended periods of abstinence followed by relapse to heavy drinking. Decades of evidence have clearly shown that long-term, chronic ethanol exposure produces brain damage in humans. The article aims to review the relationship between alcohol use and dementia. Medline and Google Scholar searches were conducted for relevant articles, chapters and books published until 2019. Search terms used included alcohol consumption, alcohol-related dementia, alcohol use disorders, chronic alcoholism, dementia. Publications found through this indexed search were reviewed for further relevant references. Alcohol acts on the central nervous system via both direct and indirect effects, frequently a combination of the two. There is consensus that alcohol contributes to the acquisition of cognitive deficits in late life. However, there are doubts regarding the aetiopathogenesis, nosological status and prevalence of alcohol-related dementia and still, there is much debate over how much alcohol consumption will lead to alcohol-related dementia.

Examining the Subacute Effects of Mild Traumatic Brain Injury Using a Traditional and Computerized Neuropsychological Test Battery.

This study investigates subacute cognitive effects of mild traumatic brain injury (MTBI) in the Trondheim Mild TBI Study, as measured, in part, by the neuropsychological test battery of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) program, including computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and traditional paper-and-pencil tests. We investigated whether cognitive function was associated with injury severity: intracranial traumatic lesions on neuroimaging, witnessed loss of consciousness (LOC), or post-traumatic amnesia (PTA) >1 h. Further, we explored which of the tests in the CENTER-TBI battery might be associated with the largest subacute effects of MTBI (i.e., at 2 weeks post-injury). We recruited 177 patients with MTBI (16-59 years of age) from a regional trauma center and an outpatient clinic,79 trauma control participants, and 81 community control participants. The MTBI group differed from community controls only on one traditional test of processing speed (coding; p = 0.009, Cliff's delta [Δ] = 0.20). Patients with intracranial abnormalities performed worse than those without on a traditional test (phonemic verbal fluency; p = 0.043, Δ = 0.27), and patients with LOC performed differently on the Attention Switching Task from the CANTAB (p = 0.020, Δ = -0.20). Patients with PTA >1 h performed worse than those with <1 h on 10 measures, from traditional tests and the CANTAB (Δ = 0.33-0.20), likely attributable, at least in part, to pre-existing differences in intellectual functioning between groups. In general, those with MTBI had good neuropsychological outcome 2 weeks after injury and no particular CENTER-TBI computerized or traditional tests seemed to be more sensitive to subtle cognitive deficits.

[The relationship between inflammation, cognitive disorders and neuroimaging data in schizophrenia]. / Svyaz' mezhdu vospaleniem, kognitivnymi narusheniyami i dannymi neirovizualizatsii pri shizofrenii.

OBJECTIVE: To search for the relationship between the results of functional imaging, immunological parameters and laboratory markers of inflammation in schizophrenia, taking into account cognitive impairment in patients, and to consider the possibility of using a multidisciplinary approach to diagnosis, treatment and prognosis of schizophrenia. MATERIAL AND METHODS: The study included 25 patients with schizophrenia and 13 healthy volunteers. Psychiatric scales were administered to evaluate the patient's condition. The main indicators of humoral immunity, the level of markers of inflammation, key pro-inflammatory and anti-inflammatory cytokines, and growth factor VEGF were determined by ELISA. Brain MRI was performed. All calculated tractographic data are included in the connection database to study the effect of immunological markers and the degree of severity of cognitive impairment. RESULTS AND CONCLUSION: Levels of markers of systemic inflammation and growth factor VEGF-A as well as the activation of humoral immunity are increased in patients with schizophrenia compared with controls. For the first time, the relationship of immunological parameters with the coefficient of quantitative anisotropy in the area of the corpus callosum in schizophrenia was revealed. The results indicate the possible value of indicators of the activation of the humoral immune response and systemic inflammation as markers of neurophysiological changes and cognitive dysfunction in schizophrenia.

Perioperative Assessment of Cerebellar Masses and the Potential for Cerebellar Cognitive Affective Syndrome.

The cerebellum was long perceived to be a region of limited importance with primary functions in the regulation of motor control. A degree of its functional topography in motor modulation has been traditionally appreciated. However, an evolving body of evidence supports its role in a range of cognitive processes, including executive decision making, language, emotional processing, and working memory. To this end, numerous studies of cerebellar stroke syndromes as well as investigations with functional magnetic resonance imaging and diffusion tensor imaging have given clinicians a better model of the functional topography within the cerebellum and the essential lanes of communication with the cerebrum. With this deeper understanding, neurosurgeons should integrate these domains into the perioperative evaluation and postoperative rehabilitation of patients with cerebellar tumors. This review aims to discuss these understandings and identify valuable tools for implementation into clinical practice.

Extracranial Carotid Artery Stenosis: The Effects on Brain and Cognition with a Focus on Resting-State Functional Connectivity.

Extracranial carotid artery stenosis (ECAS) due to the presence of atherosclerotic plaque is a well-known risk factor for stroke. Several structural imaging studies have investigated the effect of ECAS on the brain, focusing on structural damage (in particular cerebral small vessel disease) and on the rearrangement of the cerebral circulation. For example, it is known from the literature an association between carotid stenosis and cerebral small vessel disease, and it is also noted that a series of compensatory mechanisms are activated by the cerebrovascular system in order to overcome the cerebral hypoperfusion that is induced by the ECAS. Several neurocognitive studies have also investigated the association of ECAS with cognitive deficits. While the evidence tends to favor a direct association between ECAS and cognition, the actual relationship remains controversial. In the last decade, various resting-state functional connectivity (rs-fc) magnetic resonance (MR) studies have tried to elucidate the "in vivo" mechanisms underlying the cognitive impairment observed in these patients. Although these studies have been performed on small cohorts of patients without standardized protocols, it is plausible that in the future, such studies will help find early stage markers of cognitive impairment. This could permit an extension of indications for revascularization for the treatment of cognitive impairment in selected patients. The aim of this narrative review is to discuss the current knowledge on the effects of ECAS on brain and cognition by analyzing the main evidence from animal and clinical studies, with a special focus on rs-fc MR studies.

Microstructural brain abnormalities in HIV+ individuals with or without chronic marijuana use.

OBJECTIVE: Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+. METHOD: Using a 2 × 2 design, 44 HIV+ participants [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)] were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions. RESULTS: Compared to SN and regardless of MJ use, the HIV+ group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p < 0.001-0.050), as well as poorer cognition in Fluency (p = 0.039), Attention/Working Memory (p = 0.009), Learning (p = 0.014), and Memory (p = 0.028). Regardless of HIV serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.024) but similar cognition as nonusers. HIV serostatus and MJ use showed an interactive effect on mean diffusivity in the right globus pallidus but not on cognitive function. Furthermore, lower FA in left anterior internal capsule predicted poorer Fluency across all participants and worse Attention/Working Memory in all except SN subjects, while higher diffusivities in several white matter tracts also predicted lower cognitive domain Z-scores. Lastly, MJ users with or without HIV infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule, and globus pallidus. CONCLUSIONS: Our findings suggest that, except in the globus pallidus, chronic MJ use had no additional negative influence on brain microstructure or neurocognitive deficits in HIV+ individuals. However, lower AD in the uncinate fasciculus of MJ users suggests axonal loss in this white matter tract that connects to cannabinoid receptor rich brain regions that are involved in verbal memory and emotion. Furthermore, the greater than normal age-dependent FA declines in the white matter tracts and globus pallidus in MJ users suggest that older chronic MJ users may eventually have lesser neuronal integrity in these brain regions.

Novel approaches to quantify CNS involvement in children with Pompe disease.

OBJECTIVE: To characterize the extent of CNS involvement in children with Pompe disease using brain MRI and developmental assessments. METHODS: The study included 14 children (ages 6-18 years) with infantile Pompe disease (IPD) (n = 12) or late-onset Pompe disease (LOPD) (n = 2) receiving enzyme replacement therapy. White matter (WM) hyperintense foci seen in the brain MRIs were systematically quantified using the Fazekas scale (FS) grading system with a novel approach: the individual FS scores from 10 anatomical areas were summed to yield a total FS score (range absent [0] to severe [30]) for each child. The FS scores were compared to developmental assessments of cognition and language obtained during the same time period. RESULTS: Mild to severe WM hyperintense foci were seen in 10/12 children with IPD (median age 10.6 years) with total FS scores ranging from 2 to 23. Periventricular, subcortical, and deep WM were involved. WM hyperintense foci were seen throughout the path of the corticospinal tracts in the brain in children with IPD. Two children with IPD had no WM hyperintense foci. Children with IPD had relative weaknesses in processing speed, fluid reasoning, visual perception, and receptive vocabulary. The 2 children with LOPD had no WM hyperintense foci, and high scores on most developmental assessments. CONCLUSION: This study systematically characterized WM hyperintense foci in children with IPD, which could serve as a benchmark for longitudinal follow-up of WM abnormalities in patients with Pompe disease and other known neurodegenerative disorders or leukodystrophies in children.

Psychological functioning, brain morphology, and functional neuroimaging in Klinefelter syndrome.

Klinefelter syndrome (KS; 47,XXY) impacts neurodevelopment and is associated with an increased risk of cognitive, psychological and social impairments, although significant heterogeneity in the neurodevelopmental profile is seen. KS is characterized by a specific cognitive profile with predominantly verbal deficits, preserved function in non-verbal and visuo-spatial domains, executive dysfunction and social impairments, and by an increased vulnerability toward psychiatric disorders. The neurobiological underpinnings of the observed neuropsychological profile have not been established. A distinct pattern of both global and regional brain volumetric differences has been demonstrated in addition to preliminary findings of functional brain alterations related to auditory, motor, language and social processing. When present, the combination of cognitive, psychological and social challenges has the potential to negatively affect quality of life. This review intends to provide information and insight to the neuropsychological outcome and brain correlates of KS. Possible clinical intervention and future directions of research will be discussed.

Association of High-Density Lipoprotein Cholesterol With Cognitive Function: Findings From the PROspective Study of Pravastatin in the Elderly at Risk.

Objective: We aimed to examine whether variability in high-density lipoprotein cholesterol (HDL-c) over time was associated with cognitive function. Method: We conducted a post hoc analysis of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. Our sample included 4,428 participants with at least two repeated HDL-c measures between Months 3 and 24 postbaseline and with cognitive assessments at Month 30. HDL-c variability was defined as the intraindividual standard deviation over each person's repeated measurements. Results: Higher HDL-c variability was associated with worse performance on the Letter-Digit Coding Test (ß [95% confidence interval] [CI] = -4.39 [-7.36, -1.43], p = .004), immediate recall on the 15-Picture Learning Test (ß [95% CI] = -0.98 [-1.86, -0.11], p = .027), and delayed recall on the 15-Picture Learning Test (ß [95% CI] = -1.90 [-3.14, -0.67], p = .002). The associations did not vary by treatment group. Discussion: Our findings suggest that variability in HDL-c may be associated with poor cognitive function among older adults.

Early putamen hypertrophy and ongoing hippocampus atrophy predict cognitive performance in the first ten years of relapsing-remitting multiple sclerosis.

BACKGROUND: The first years of relapsing-remitting multiple sclerosis (RRMS) constitute the most vulnerable phase for the progression of cognitive impairment (CImp), due to a gradual decrease of compensatory mechanisms. In the first 10 years of RRMS, the temporal volumetric changes of deep gray matter structures must be clarified, since they could constitute reliable cognitive biomarkers for diagnostic, prognostic, and therapeutic purposes. METHODS: Forty-five cognitively asymptomatic patients with RRMS lasting ≤ 10 years, and with a brain MRI performed in a year from the neuropsychological evaluation (Te-MRI), were included. They performed the Brief International Cognitive Assessment battery for MS. Thirty-one brain MRIs performed in the year of diagnosis (Td-MRI) and 13 brain MRIs of age- and sex-matched healthy controls (HCs) were also included in the study. The relationships between clinical features, cognitive performances, and Te- and Td-MRI volumes were statistically analyzed. RESULTS: Cognitively preserved (CP) patients had significantly increased Td-L-putamen (P = 0.035) and Td-R-putamen volume (P = 0.027) with respect to cognitively impaired (CI) ones. CI patients had significantly reduced Te-L-hippocampus (P = 0.019) and Te-R-hippocampus volume (P = 0.042) compared, respectively, with Td-L-hippocampus and Td-R-hippocampus volume. Td-L-putamen volume (P = 0.011) and Te-L-hippocampus volume (P = 0.023) were independent predictors of the Symbol Digit Modalities Test score in all patients (r2 = 0.31, F = 6.175, P = 0.001). CONCLUSION: In the first years of RRMS, putamen hypertrophy and hippocampus atrophy could represent promising indices of cognitive performance and reserve, and become potentially useful tools for diagnostic, prognostic, and therapeutic purposes.