Association of plasma IL-6 and soluble IL-6 receptor levels with the Asp358Ala polymorphism of the IL-6 receptor gene in schizophrenic patients

Recent studies indicate a role of excessive interleukin-6 (IL-6) signaling in the pathogenesis of schizophrenia. A previous study reported a significant association of schizophrenia with the IL-6 receptor (IL-6R) gene Asp358Ala polymorphism, which is known to regulate circulating IL-6 and soluble IL-6R (sIL-6R) levels in healthy subjects. To further examine the influence of the polymorphism in schizophrenic patients, we compared the plasma levels of IL-6 and sIL-6R between schizophrenic patients and healthy controls for each genotype of the Asp358Ala polymorphism. Asp358Ala genotyping and plasma IL-6 level measurements were performed in 104 patients with schizophrenia and 112 healthy controls. Of these participants, 53 schizophrenic patients and 49 controls were selected for the measurement of plasma sIL-6R levels. A two-way factorial analysis of covariance was performed with the transformed plasma levels as the dependent variable, diagnosis and genotype as independent variables, and sex and age as covariates. No significant diagnosis × genotype interaction was observed for IL-6 and sIL-6R levels. The Ala allele of Asp358Ala was significantly associated with higher levels of both IL-6 and sIL-6R. IL-6 levels were significantly elevated in schizophrenic patients compared to those in controls, whereas no significant difference in sIL-6R levels was observed between schizophrenic patients and controls. Our findings suggest that the presence of schizophrenia is associated with elevated IL-6 levels, whereas sIL-6R levels are mainly predetermined by the Asp358Ala genotype and are not associated with the disease status. Increased IL-6 levels without alterations in sIL-6R levels may result in excessive IL-6 signaling in schizophrenia.     

Cognition in multiple system atrophy: neuropsychological profile and interaction with mood

We evaluated cognitive functions and mood in two groups of patients with multiple system atrophy (MSA) in order to determine the influence of mood on cognitive performance. Our aim was to differentiate between parkinsonism-predominant (MSA-P) and cerebellar-predominant (MSA-C) MSA based on those parameters. Fifteen MSA-P and 10 MSA-C patients underwent neuropsychological tests that examined executive functions (working memory, response inhibition, and verbal reproduction), verbal learning and memory, verbal and visual reasoning, and processing speed. Anxiety and depression were also assessed. The findings on their cognitive performance and mood were compared to those of healthy controls and also discussed in relation to a group of Parkinson’s disease (PD) patients. The results showed that cognitive and mood characteristics could distinguish MSA-P from MSA-C and that anxiety and depression are related to cognitive decline. Compared with healthy controls, MSA-P patients showed reduced verbal retrieval (immediate, P < 0.019; long-term, P < 0.018) while MSA-C patients had difficulties in learning new verbal information (P < 0.022) and in controlling attention (P < 0.023). These data indicate that MSA-P and MSA-C appear to have, at least in part, different cognitive and mood profiles. The neuropsychological assessments of MSA patients should test for and then take into account their level of anxiety and depression, insofar as it might have an adverse effect on their cognitive performance.     

Inflammatory cytokine levels implicated in Alzheimer’s disease moderate the effects of sex on verbal memory performance

Despite having an initial verbal memory advantage over men, women have greater rates of Alzheimer’s disease and more rapid cognitive decline once diagnosed. Moreover, although Alzheimer’s disease is influenced by inflammation, which itself has known sex differences, no study has investigated whether sex differences in memory are moderated by peripheral inflammatory activity. To address this issue, we analyzed data from 109 individuals (50 women, M_age = 71.62, range = 55–87) diagnosed as cognitively normal, or having mild cognitive impairment or Alzheimer’s disease dementia. We then followed the sample for 12 months, as part of a longitudinal study of aging and Alzheimer’s disease. At baseline, we assessed levels of the inflammatory cytokines interleukin (IL)-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in plasma. At baseline and 12 months, we assessed verbal memory using the Rey Auditory Verbal Learning Test and nonverbal memory using the Brief Visuospatial Memory Test-Revised. As hypothesized, for the full sample, women exhibited stronger verbal (but not nonverbal) memory than men. In women, but not men, higher IL-1β at baseline related to poorer verbal learning across both time points and delayed recall at 12 months. The effect of sex on memory also differed by IL-1β level, with women exhibiting a memory advantage both at baseline and 12 months, but only for those with low-to-moderate IL-1β levels. Therefore, high peripheral inflammation levels may lead to a sex-specific memory vulnerability relevant for Alzheimer’s disease.     

Cognitive changes in people with temporal lobe epilepsy over a 13-year period

ObjectivesThe aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13 years and to determine what clinical and treatment characteristics may have been associated with these.Materials and methodsThirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13 years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13 years earlier.ResultsThere was no significant change in verbal and verbal–logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal–logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal–logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal–logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression.ConclusionOver a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study.     

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Nine patients with OLE, ages 8–29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG‐PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups

The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.     

Cognitive function in the locked-in syndrome

Objective The lockedin syndrome (LIS) originates from a ventro-pontine lesion resulting in a complete quadraplegia and anarthria. Classically, communication remains possible by means of spared vertical eye movements and/or blinking. To allow assessing cognitive functions in LIS patients, we propose here a neuropsychological testing based on eye-coded communication. Methods Ten chronic LIS survivors were assessed 1 to 6 years after their brain insult.One patient was evaluated subacutely (at 2 months) and retested at 6 and 16 months.Neuropsychological testing encompassed short- and long-term memory, attention, executive functioning, phonological and semantic processing and verbal intelligence. Results None of the patients showed alterations in verbal intelligence. Impairments in one or several tests were found in five patients. In three of these patients, neuropsychological deficits could be related to additional cortical or thalamic structural brain lesions. In the other 2 patients, weakness or signs of fatigue only were observed in one or two cognitive tasks. Repeated measures in a subacute patient with pure brainstem lesion indicate the recovery of good levels of cognition 6 months after injury. Conclusion Results indicate that LIS patients can recover intact cognitive levels in cases of pure brainstem lesions, and that additional brain injuries are most likely responsible for associated cognitive deficits in the LIS. Furthermore, a systematic neuropsychological assessment in LIS patients would allow detecting their cognitive deficits,which will contribute to improve their quality of life and of communication with family and medical caretakers. * The Coma Science Group.     

Emotional discomfort and impairments in verbal memory in schizophrenia

Research has demonstrated that impairments in verbal memory in schizophrenia are linked with psychosocial deficits. Less is known, however, about their relationship to clinical features of illness. This study explores the hypothesis that impairments in verbal memory, particularly forms of memory requiring deeper levels of encoding, are uniquely linked to symptoms of dysphoria or emotional discomfort. Accordingly, we examined the association between concurrent measures of symptoms and verbal memory for 84 subjects with schizophrenia. Measures of positive, negative, cognitive, excitement and emotional discomfort symptoms were derived from factor scores of the Positive and Negative Syndrome Scale. Verbal memory was assessed using two tests requiring relatively superficial levels of encoding: The Hopkins Verbal Memory Test and the Digit Span subtest; and one test requiring deeper levels of encoding: the Logical Memory subtests I and II. As predicted, multiple regressions controlling for age, education and attention revealed that poorer performance on Logical Memory was strongly associated with greater levels of emotional discomfort (R(2)=0.22 and 0.25, respectively) while performance on the Hopkins test was related to cognitive symptoms scores (R(2)=0.08 and 0.09, respectively). Implications for the conceptualization of verbal memory deficits in schizophrenia are discussed.     

Evaluation of cognitive function in bipolar disorder using the Brief Assessment of Cognition in Affective Disorders (BAC-A)

BackgroundAlthough cognitive impairment is a core feature of bipolar disorder (BD) there is no instrument of choice for the assessment of bipolar patients. The aim of this study is to assess cognitive performance using the Brief Assessment of Cognition in Affective Disorders (BAC-A), a comprehensive test battery developed specifically for BD, and determine its suitability to estimate global functioning.MethodsThe BAC-A was administered to 93 BD patients (M ± S.E: 35.18 ± 1.39 years) and 56 healthy controls (HC – M ± S.E: 36.17 ± 1.91 years). The scores of the BAC-A were combined in eight summary scores: visuomotor, immediate affective and non-affective memory, verbal fluency, delayed affective and non-affective memory, inhibition, and problem solving. Post hoc analyses were performed on subtests of the summary scores found to be significantly different between BD patients and HC. Correlational analyses explored the association between the Global Assessment of Functioning (GAF) score and cognitive functioning.ResultsCompared to HC, BD patients showed a significant impairment in short-term non-affective memory and verbal fluency. Poorer performance in verbal memory and verbal fluency summary scores correlated positively with reduced GAF.ConclusionsOur results are consistent with previous reports of verbal memory and verbal fluency impairment in BD. The deficits in short-term memory and semantic fluency may indicate inefficient learning strategies and/or difficulties in retrieving information. The BAC-A could be used to estimate global functioning in BD patients.     

Short-latency afferent inhibition predicts verbal memory performance in patients with multiple sclerosis

Background   The pathogenesis of cognitive deficits in multiple sclerosis (MS) patients is the subject of debate. A causative role of grey matter impairment has been suggested. Acetylcholinesterase inhibitors have been proposed in the treatment of cognitive impairment in MS. Short-latency afferent inhibition (SAI) is a cortical phenomenon assessed by a transcranial magnetic stimulation protocol that provides an in vivo index of central cholinergic function. Methods   We recruited 20 consecutive relapsing-remitting or secondary progressive MS patients showing normal upper limb somatosensory and motor evoked potentials. SAI of the left-hand motor cortex from median nerve stimuli was tested. A matched group of 20 healthy subjects was also assessed. All patients underwent neuropsychological assessment with Rao’s Brief Repeatable Battery (BRB). Multiple regression was performed on the number of failed tests and on scores of single BRB tests as dependent variables with Extended Disability Status Scale (EDSS) score, SAI, age, gender and disease duration as regressors. Patients with impaired SAI, were reassessed after a single oral dose of rivastigmine. Results   SAI was a significant predictor of the score in tests that assess verbal memory. EDSS score and age were found as predictors of the other BRB tests. SAI was significantly improved by oral rivastigmine. Conclusions   Our data confirm that cognitive impairment in MS is multifactorial. The performances in the subdomain of verbal memory are predicted by SAI. These results favour the hypothesis of grey matter involvement and suggest a role of acetylcholine dysfunction in the pathogenesis of some aspects of cognitive deficits in MS.     

Presurgical neuropsychological testing predicts cognitive and seizure outcomes after anterior temporal lobectomy

We sought to determine significant predictors of seizure and cognitive outcome following surgery for epilepsy. Participants included 41 patients who had undergone anterior temporal lobectomy (ATL). Higher presurgical verbal/language scores and lower nonverbal memory scores were predictive of seizure-free status following ATL. Overall, the presurgical predictors were 93% accurate in discriminating between seizure-free and non-seizure-free patients postsurgery. Surgery in the nondominant-for-language hemisphere was predictive of higher postsurgical verbal/language and verbal memory scores. Higher presurgical visual/construction, nonverbal memory, and verbal/language scores were predictive of better postsurgical verbal/language functioning. Better presurgical verbal/language functioning was predictive of the same skills postsurgically as well as visual/construction outcomes. Exploratory analyses in a subset of participants (n = 25) revealed that dominant and nondominant intracarotid amobarbital (Wada) memory scores added unique variance only for predicting nonverbal memory following ATL. Presurgical neuropsychological testing provides significant and unique information regarding postsurgical seizure freedom and cognitive outcome in patients who have undergone ATL.     

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy

ObjectiveTemporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance.MethodsThirty-four patients (right TLE = 17, left TLE = 17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests.ResultsThe number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume.ConclusionIn patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity.     

Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome

Objective  This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Methods  Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Results  Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Conclusion  Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.     

Early-onset bipolar disorder: how about visual-spatial skills and executive functions?

Early-onset bipolar disorder is an impairing condition that is strongly associated with genetic inheritance. Neurocognitive deficits are core traits of this disorder which seem to be present in both young and adult forms. Deficits in verbal memory and attention are persistent within euthymic phases in bipolar adults, adolescents, and children. In younger samples, including type I or II and not otherwise specified patients, executive functions are not widely impaired and the existence of visual-spatial deficits remains unclear. The main aim of this study was to compare the neurocognitive performance in young stabilized type I or II bipolar patients and healthy controls. Fifteen medicated adolescents with bipolar disorder and 15 healthy adolescents, matched in age and gender, were compared on visual-spatial skills (reasoning, memory, visual–motor accuracy) and executive functioning (attention and working memory, set-shifting, inhibition) using t-tests and MANCOVA. Correcting for verbal competence, MANCOVA showed that patients performed significantly worse than controls in letters and numbers sequencing (P = 0.003), copy (P < 0.001) and immediate recall (P = 0.007) of the Rey Complex Figure Test, interference of the Stroop Color-Word Test (P = 0.007) and non-perseverative errors on the Wisconsin Card Sorting Test (P = 0.038). Impaired cognitive performance was found in young bipolar patients in working memory, visual-motor skills, and inhibitory control.     

Cognitive profile in Wilson's disease: A case series of 31 patients

BackgroundWilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. If untreated, WD, which is initially a liver disease, can turn into a multi-systemic disease with neurological involvement. Very few studies have described cognitive impairment in WD. The aim of this study is to report the cognitive profile of 31 treated WD patients.MethodsPatients were classed into two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients without neurological signs (WD-N^?) (n = 13), and WD patients with neurological signs (WD-N⁺) (n = 18). The patients participated in a neuropsychological assessment evaluating memory, executive function and visuo-spatial abilities.ResultsBoth groups performed well for verbal intelligence and episodic memory skills. However, the majority of these patients exhibited altered performance for at least one cognitive test, particularly in the executive domain. The WD-N⁺ group performed less well than the WD-N^? group on cognitive tests involving rapid motor function, abstract thinking, working memory and top-down inhibitory control.ConclusionsCognitive impairment in treated WD patients essentially affects executive function involving fronto-striatal circuits. Verbal intelligence and episodic memory abilities seem to be remarkably preserved. Neuropsychological assessment is a valuable tool to evaluate the presence and the consequences of these cognitive impairments in WD patients with or without neurological signs in the course of this chronic disease.     

Subjective cognitive concerns,episodic memory,and the APOE ε4 allele

BackgroundSubjective cognitive concerns may represent a simple method to assess likelihood of memory decline among apolipoprotein E (APOE) ε4 carriers.MethodsWe examined the relationship of self-reported subjective cognitive concerns, using seven specific cognitive concerns, with memory and memory decline over 6 years among APOE ε4 carriers and non-carriers from the Nurses' Health Study.ResultsIn both groups, increasing subjective cognitive concern score predicted worse baseline memory and faster rates of subsequent memory decline, after adjustment for age, education and depression. The relation with baseline memory appeared statistically stronger in APOE ε4 carriers (P-interaction = 0.03). For memory decline, mean differences in slopes of episodic memory (95% CI) for 4 to 7 versus no concern = −0.05 (−0.10, 0.01) standard units in APOE ε4 carriers, and −0.04 (−0.08, −0.01) standard units in non-carriers.ConclusionsAPOE ε4 carriers with self-assessed cognitive concerns appear to have worse memory, and possibly accelerated memory decline.     

Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden infant death syndrome

Mild infection may trigger sudden death in the vulnerable infant by cytokine interactions with a compromised medullary serotonergic (5-HT) system, leading to disrupted cardiorespiratory regulation and sleep-related sudden death. The cytokine interleukin (IL)-6 is elevated in the cerebrospinal fluid in SIDS. We tested the hypothesis that the expression of IL-6 receptors (IL-6R) and/or gp130 (involved in IL-6R signaling) is altered in the medullary 5-HT system in SIDS. Immunohistochemistry of IL-6R and gp130 was performed on medullae from 25 SIDS infants, 20 infectious deaths, and 14 controls using a semi-quantitative grading system. In the SIDS cases, mean IL-6R intensity grade in the arcuate nucleus (major component of medullary 5-HT system) was significantly higher than in the control group (2.00 ± 0.07 vs. 1.77 ± 0.08, P = 0.04), with no other differences in IL-6R or gp130 expression at any other site. Arcuate 5-HT neurons expressed IL-6R, indicating a site of IL-6/5-HT interaction. In SIDS, IL-6R expression is abnormal in the arcuate nucleus, the putative human homolog of rodent ventral medullary chemosensitivity sites involving 5-HT. Aberrant interactions between IL-6 and the arcuate nucleus may contribute to impaired responses to hypercapnia generated by infection (hyper-metabolism) combined with rebreathing.     

The relationship between impairment of voluntary movements and cognitive impairment in Huntington’s disease

The relationship between motor symptoms and cognitive impairment in Huntington’s disease (HD) is still discussed. We analysed 45 HD patients in various stages using Unified Huntington’s Disease Rating Scale motor subscale (voluntary and involuntary components were evaluated separately), verbal memory and executive functions tests. Partial correlations controlling for HD duration and age were used to estimate the relationships among factor scores for motor and cognitive impairment. Voluntary components of motor performance were found to be significantly correlated with verbal short-term memory disturbances (r = −0.361, P = 0.03), with tests of executive functions more dependent on motor performance (r = 0.640, P < 0.01) and also with tests of executive functions less dependent on motor performance (r = 0.461, P < 0.01). Involuntary components did not correlate significantly with any part of cognitive performance.     

Cognitive changes in patients with Huntington’s disease (HD) and asymptomatic carriers of the HD mutation

OBJECTIVE: Objective information about the onset and progression of cognitive impairment in Huntington's disease (HD) is very important in the light of appropriate outcome measures when conducting clinical trials. Therefore, we evaluated the progression of cognitive functions in HD patients and asymptomatic carriers of the HD mutation (AC) over a 2.5-year period.We also sought to detect the earliest markers of cognitive impairment in AC. METHODS: A prospective study comparing HD patients, clinically asymptomatic HD mutation-carriers (AC) and non-carriers (NC). These groups were examined three times during a period of 2.5 years. At baseline the study sample consisted of 49 subjects. Forty-two subjects (19 HD patients, 12 AC and 11 NC) completed three assessments. A battery of neuropsychological tests measuring intelligence, attention, memory, language, visuospatial perception, and executive functions was performed. RESULTS: The performance of HD patients deteriorated on the following cognitive tests: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word, Boston Naming Test (BNT), Object and Space Perception and Trail Making Test-B. Longitudinal comparison of AC and NC revealed that performances on SDMT, Block Span, Digit Span Backwards, Hopkins Verbal Learning Test (learning and delayed recall) and Conditional Associative Learning Test are impaired in AC. CONCLUSIONS: Tasks measuring mainly attention, object and space perception and executive functions adequately assess the progression of HD disease. Other cognitive functions do not significantly deteriorate. Furthermore, problems in attention, working memory, verbal learning, verbal long-term memory and learning of random associations are the earliest cognitive manifestations in AC.     

Cognitive deficits associated with acquired amusia after stroke: A neuropsychological follow-up study

Recent evidence on amusia suggests that our ability to perceive music might be based on the same neural resources that underlie other higher cognitive functions, such as speech perception and spatial processing. We studied the neural correlates of acquired amusia by performing extensive neuropsychological assessments on 53 stroke patients with a left or right hemisphere middle cerebral artery (MCA) stroke 1 week, 3 months, and 6 months after the stroke. In addition, structural magnetic resonance imaging (MRI) was performed on all patients 1 week and 6 months post-stroke. Based on their performance on a shortened version of the Montreal Battery of Evaluation of Amusia (MBEA), the patients were classified as amusic (n = 32) or non-amusic (n = 21). MRI results showed that the incidence of auditory cortex and frontal lobe damage was significantly higher in the amusic group than in the non-amusic group, but the two groups did not differ in respect to lesion laterality. Cognitively, amusia was associated with general deficits in working memory and learning, semantic fluency, executive functioning, and visuospatial cognition, as well as hemisphere-specific deficits in verbal comprehension, mental flexibility, and visuospatial attention (unilateral spatial neglect). Moreover, the recovery of music perception ability was related to the recovery of verbal learning, visuospatial perception and attention, and focused attention, especially in amusic patients. Together, these results suggest the ability to perceive music is closely linked to other higher cognitive functions.