Graph lesion-deficit mapping of fluid intelligence.

Fluid intelligence is arguably the defining feature of human cognition. Yet the nature of its relationship with the brain remains a contentious topic. Influential proposals drawing primarily on functional imaging data have implicated 'multiple demand' frontoparietal and more widely distributed cortical networks, but extant lesion-deficit studies with greater causal power are almost all small, methodologically constrained, and inconclusive. The task demands large samples of patients, comprehensive investigation of performance, fine-grained anatomical mapping, and robust lesion-deficit inference, yet to be brought to bear on it. We assessed 165 healthy controls and 227 frontal or non-frontal patients with unilateral brain lesions on the best-established test of fluid intelligence, Raven's Advanced Progressive Matrices, employing an array of lesion-deficit inferential models responsive to the potentially distributed nature of fluid intelligence. Non-parametric Bayesian stochastic block models were used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects. Impaired performance was confined to patients with frontal lesions [F(2,387) = 18.491; P < 0.001; frontal worse than non-frontal and healthy participants P < 0.01, P <0.001], more marked on the right than left [F(4,385) = 12.237; P < 0.001; right worse than left and healthy participants P < 0.01, P < 0.001]. Patients with non-frontal lesions were indistinguishable from controls and showed no modulation by laterality. Neither the presence nor the extent of multiple demand network involvement affected performance. Both conventional network-based statistics and non-parametric Bayesian stochastic block modelling heavily implicated the right frontal lobe. Crucially, this localization was confirmed on explicitly disentangling functional from pathology-driven effects within a layered stochastic block model, prominently highlighting a right frontal network involving middle and inferior frontal gyrus, pre- and post-central gyri, with a weak contribution from right superior parietal lobule. Similar results were obtained with standard lesion-deficit analyses. Our study represents the first large-scale investigation of the distributed neural substrates of fluid intelligence in the focally injured brain. Combining novel graph-based lesion-deficit mapping with detailed investigation of cognitive performance in a large sample of patients provides crucial information about the neural basis of intelligence. Our findings indicate that a set of predominantly right frontal regions, rather than a more widely distributed network, is critical to the high-level functions involved in fluid intelligence. Further they suggest that Raven's Advanced Progressive Matrices is a useful clinical index of fluid intelligence and a sensitive marker of right frontal lobe dysfunction.

A Bayesian predictive processing account of Othello syndrome in Parkinson's disease.

Introduction: Although delusions in Parkinson's disease (PD) are rare, when they occur they frequently take the form of "Othello syndrome": the irrational belief that a spouse or partner is being unfaithful. Hitherto dismissed as either a by-product of dopamine therapy or cognitive impairment, there are still no convincing theoretical accounts to explain why only some patients fall prey to this delusion, or why it persists despite clear disconfirmatory evidence.Methods: We discuss the limitations of existing explanations of this delusion, namely hyperdopaminergia-induced anomalous perceptual experiences and cognitive impairment, before describing how Bayesian predictive processing accounts can provide a more comprehensive explanation by foregrounding the importance of prior experience and its impact upon computation of probability. We illustrate this new conceptualisation with three case vignettes.Results: We suggest that in those with prior experience of romantic betrayal, hyperdominergic-induced aberrant prediction errors enable anomalous perceptual experiences to accrue greater prominence, which is then maintained through Bayes-optimal inferencing to confirm cognitive distortions, eliciting and shaping this dangerous delusion.Conclusions: We propose the first comprehensive mechanistic account of Othello syndrome in PD and discuss implications for clinical interventions.

Long-term study of the cognitive profile of Moyamoya Disease in adults.

Moyamoya Disease (MMD) is a rare cerebrovascular disorder which can have significant cognitive consequences. The aim of the current study was to describe comprehensively the domain-specific cognitive profile of adult patients with MMD and to assess whether this changes in the absence of recurrent stroke over long-term follow-up. Comprehensive neuropsychological assessment covering seven cognitive domains was conducted on 61 adult patients with MMD at baseline and then at up to 3 further time points during follow up (median=2.31, 4.87 and 7.12 years). Although 27 patients had had prior surgical revasculariation, none had surgery between neuropsychological assessments. Cognitive impairment was common. At baseline, impairment in executive functions was most frequent (57%), followed by performance IQ (36%), speed of information processing (31%) and visual memory (30%). We found that the neuropsychological profile remains broadly stable over long-term follow-up with no clear indication of improvement or significant decline. The pattern of impairment also did not differ depending on age of onset or whether there was a history of either prior stroke at presentation or revascularisation surgery at presentation.

Cognitive dysfunction and white matter hyperintensities in Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder with multi-system involvement including cerebrovascular disease. Patients with FD also have a high risk of ischaemic stroke and TIA. White matter hyperintensities are common, but their clinical impact on cognition remains uncertain. Previous studies have examined the neuropsychological profile of FD, but have been inconclusive in part due to methodological limitations including small sample sizes. We sought to address these limitations in a case-control study of 26 patients with Fabry disease with mild to moderate disease symptoms matched with 18 healthy controls for age and premorbid intellectual level. We obtained detailed neuropsychological data and MRI neuroimaging data on the severity of white matter changes. Mood was accounted for as a possible confounder. Our results showed significant compromise of executive functions and information processing speed for the FD group. Error analyses suggested that the compromise of executive functions could not be entirely accounted for by slowed information processing speed. We demonstrated significant correlations between cognitive decline and the overall volume of white matter hyperintensities in the FD group. Our results point to significant compromise of cognition in FD even without stroke or mood difficulties. This suggests that neuropsychological assessment and rehabilitation should be routinely offered to patients with FD.

Is the Weigl Colour-Form Sorting Test Specific to Frontal Lobe Damage?

OBJECTIVE: The Weigl Colour-Form Sorting Test is a brief, widely used test of executive function. So far, it is unknown whether this test is specific to frontal lobe damage. Our aim was to investigate Weigl performance in patients with focal, unilateral, left or right, frontal, or non-frontal lesions. METHOD: We retrospectively analysed data from patients with focal, unilateral, left or right, frontal (n = 37), or non-frontal (n = 46) lesions who had completed the Weigl. Pass/failure (two correct solutions/less than two correct solutions) and errors were analysed. RESULTS: A greater proportion of frontal patients failed the Weigl than non-frontal patients, which was highly significant (p < 0.001). In patients who failed the test, a significantly greater proportion of frontal patients provided the same solution twice. No significant differences in Weigl performance were found between patients with left versus right hemisphere lesions or left versus right frontal lesions. There was no significant correlation between performance on the Weigl and tests tapping fluid intelligence. CONCLUSIONS: The Weigl is specific to frontal lobe lesions and not underpinned by fluid intelligence. Both pass/failure on this test and error types are informative. Hence, the Weigl is suitable for assessing frontal lobe dysfunction.

White matter integrity correlates with cognition and disease severity in Fabry disease.

Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10-6 mm2/s (SD 32 × 10-6) versus 720 × 10-6 mm2/s (SD 21 × 10-6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10-6 mm2/s (SD 26 × 10-6) versus 723 × 10-6 mm2/s (SD 22 × 10-6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = -0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = -0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression.

Cerebral MRI findings predict the risk of cognitive impairment in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombomicroangiopathy caused by deficiency of ADAMTS13. Acute neurological involvement is well described, but its long-term impact requires evaluation. One-hundred thirty-one patients, following an acute TTP event, with severe headache or neurological symptoms had a cerebral MRI. Fifty-six percent had abnormal imaging, more commonly in patients with neurological symptoms than headaches only (80% vs. 18%, P < 0·0001). In remission, 27% (n = 35) reported persistent cognitive symptoms: specifically, impaired memory (66%), difficulty concentrating (26%), and word-finding difficulties not secondary to an acute stroke (26%). Sixty-five percent also reported depression and 55% reported anxiety, regardless of presenting neurology. The frontal lobe was disproportionally affected in patients with marked intellectual impairment, seen in 67% of patients compared to 19% of patients without intellectual impairment (P = 0·002). The primary MRI finding in these patients was hyperintense white matter lesions. An abnormal MRI was associated with a lower median verbal IQ (85 vs. 99, P = 0·02) and performance IQ (83 vs. 100, P = 0·02). In conclusion, neurological symptoms are frequently associated with an abnormal cerebral MRI scan, and white matter frontal lobe lesions are particularly significant, leading to marked intellectual impairment. Anxiety and depression were evident in over half of patients, regardless of neurological involvement at presentation.

Cognitive Reserve Proxies Do Not Differentially Account for Cognitive Performance in Patients with Focal Frontal and Non-Frontal Lesions.

OBJECTIVE: Cognitive reserve (CR) suggests that premorbid efficacy, aptitude, and flexibility of cognitive processing can aid the brain's ability to cope with change or damage. Our previous work has shown that age and literacy attainment predict the cognitive performance of frontal patients on frontal-executive tests. However, it remains unknown whether CR also predicts the cognitive performance of non-frontal patients. METHOD: We investigated the independent effect of a CR proxy, National Adult Reading Test (NART) IQ, as well as age and lesion group (frontal vs. non-frontal) on measures of executive function, intelligence, processing speed, and naming in 166 patients with focal, unilateral frontal lesions; 91 patients with focal, unilateral non-frontal lesions; and 136 healthy controls. RESULTS: Fitting multiple linear regression models for each cognitive measure revealed that NART IQ predicted executive, intelligence, and naming performance. Age also significantly predicted performance on the executive and processing speed tests. Finally, belonging to the frontal group predicted executive and naming performance, while membership of the non-frontal group predicted intelligence. CONCLUSIONS: These findings suggest that age, lesion group, and literacy attainment play independent roles in predicting cognitive performance following stroke or brain tumour. However, the relationship between CR and focal brain damage does not differ in the context of frontal and non-frontal lesions.

Presence phenomena in parkinsonian disorders: Phenomenology and neuropsychological correlates.

INTRODUCTION: The feeling of a presence that occurs in the absence of objectively identifiable stimuli is common in parkinsonian disorders. Although previously considered benign and insignificant, recent evidence suggests that presence phenomena may act as the gateway to more severe hallucinations and dementia. Despite this, we still know relatively little about these phenomena. OBJECTIVE: To examine parkinsonian disorder patients' subjective experience of presence phenomena, and retrospectively analyse their cognitive correlates, in order to elucidate the emergence of information processing deficits in parkinsonian disorders. METHODS/DESIGN: 25 patients who endorsed presence phenomena were asked to complete a semi-structured interview about their experiences. The cognitive profiles of these patients were then compared to those of age- and education-matched patients who denied presence phenomena. RESULTS: Patients described the presence as mostly that of an unknown human with neutral valence. Patients who described it as unpleasant were noted to also demonstrate elevated anxiety. Patients who identified the presence as a known person, described it as touching them, or interacted with the presence emotionally or physically demonstrated reduced insight. Patients with presence phenomena demonstrated more frequent impairments in visual processing, executive function and speed of processing. CONCLUSIONS: Presence phenomena occur in the company of advancing cognitive impairment and involvement of the posterior cortical functions. Initially encountered as a neutral spatial skeleton, the experience is then shaped by the patient's affective state and level of insight.

The Prefrontal Cortex and Neurological Impairments of Active Thought.

This article reviews the effects of lesions to the frontal cortex on the ability to carry out active thought, namely, to reason, think flexibly, produce strategies, and formulate and realize plans. We discuss how and why relevant neuropsychological studies should be carried out. The relationships between active thought and both intelligence and language are considered. The following basic processes necessary for effective active thought are reviewed: concentration, set switching, inhibiting potentiated responses, and monitoring and checking. Different forms of active thought are then addressed: abstraction, deduction, reasoning in well-structured and ill-structured problem spaces, novel strategy generation, and planning. We conclude that neuropsychological findings are valuable for providing information on systems rather than networks, especially information concerning prefrontal lateralization of function. We present a synthesis of the respective roles of the left and right lateral prefrontal cortex in active thought.

Early detection of memory impairments in older adults: standardization of a short version of the verbal and nonverbal Recognition Memory Test.

In several neurological conditions, in elderly and cognitively impaired subjects, memory functioning must be evaluated to early detect the cognitive deterioration processes. In particular, recognition memory assessment is an essential step in the clinical and neuropsychological evaluation of early memory impairments. The Recognition Memory Test (RMT) developed by Smirni et al. (G Ital Psicol XXXVII(1):325-343, 2010) is an effective instrument to assess verbal and nonverbal recognition memory in the Italian population. The current study provides a new, brief, and reliable RMT format to evaluate recognition memory on elderly subjects and it reports normative data in an older adult Italian population sample (including 100 participants well distributed across sex, education, and age categories). The shortened version of RMT keeps the administration procedures and materials of the original Italian RMT constant, i.e., words, faces, and buildings. Multiple regression analysis revealed significant effects of age and educational level on performance but no effect of sex. Inferential cutoffs have been determined and equivalent scores computed. The availability of equivalent scores for the Recognition Memory Test will prove useful in the clinical evaluation of patients' memory profiles.

Standardization and validation of a parallel form of the verbal and non-verbal recognition memory test in an Italian population sample.

In the neuropsychological assessment of several neurological conditions, recognition memory evaluation is requested. Recognition seems to be more appropriate than recall to study verbal and non-verbal memory, because interferences of psychological and emotional disorders are less relevant in the recognition than they are in recall memory paradigms. In many neurological disorders, longitudinal repeated assessments are needed to monitor the effectiveness of rehabilitation programs or pharmacological treatments on the recovery of memory. In order to contain the practice effect in repeated neuropsychological evaluations, it is necessary the use of parallel forms of the tests. Having two parallel forms of the same test, that kept administration procedures and scoring constant, is a great advantage in both clinical practice, for the monitoring of memory disorder, and in experimental practice, to allow the repeated evaluation of memory on healthy and neurological subjects. First aim of the present study was to provide normative values in an Italian sample (n = 160) for a parallel form of a verbal and non-verbal recognition memory battery. Multiple regression analysis revealed significant effects of age and education on recognition memory performance, whereas sex did not reach a significant probability level. Inferential cutoffs have been determined and equivalent scores computed. Secondly, the study aimed to validate the equivalence of the two parallel forms of the Recognition Memory Test. The correlations analyses between the total scores of the two versions of the test and correlation between the three subtasks revealed that the two forms are parallel and the subtasks are equivalent for difficulty.

Relationship of Cognitive Function to Motor Symptoms and Mood Disorders in Patients With Isolated Dystonia.

OBJECTIVE: To investigate the relationship of dystonia symptoms to cognitive function by comparing cognitive performance in patients with focal (cervical) and generalized dystonia subtypes and examining the differential contributions of severity of symptoms and mood disorders to cognition. BACKGROUND: Studies of the nonmotor syndrome in isolated dystonia have reported evidence of cognitive dysfunction, but the cause of this impairment remains unclear. Several studies have suggested that poor cognitive performance reflects the distracting effects of the motor symptoms and/or a mood disorder. METHODS: In this retrospective study, we used an extensive battery of cognitive and mood assessments to compare 25 patients with cervical dystonia, 13 patients with generalized dystonia, and 50 healthy controls. RESULTS: We found cognitive performance to be independent of all clinical and mood variables. We found no significant differences in cognition between the two dystonia groups. The combined dystonia groups had significant impairment on only one measure of cognitive function, the Trail Making Test. Two patients were also impaired on the Stroop test, and six on the Hayling Sentence Completion Test. CONCLUSIONS: The nonmotor features of dystonia include subtle cognitive symptoms and high rates of mood disorders, both of which occur independent of motor symptom severity and level of disability. Thus, we would argue that isolated dystonia is a tripartite disorder, with motor, affective, and subtle cognitive features.

Verbal suppression and strategy use: a role for the right lateral prefrontal cortex?

Verbal initiation, suppression and strategy generation/use are cognitive processes widely held to be supported by the frontal cortex. The Hayling Test was designed to tap these cognitive processes within the same sentence completion task. There are few studies specifically investigating the neural correlates of the Hayling Test but it has been primarily used to detect frontal lobe damage. This study investigates the components of the Hayling Test in a large sample of patients with unselected focal frontal (n = 60) and posterior (n = 30) lesions. Patients and controls (n = 40) matched for education, age and sex were administered the Hayling Test as well as background cognitive tests. The standard Hayling Test clinical measures (initiation response time, suppression response time, suppression errors and overall score), composite errors scores and strategy-based responses were calculated. Lesions were analysed by classical frontal/posterior subdivisions as well as a finer-grained frontal localization method and a specific contrast method that is somewhat analogous to voxel-based lesion mapping methods. Thus, patients with right lateral, left lateral and superior medial lesions were compared to controls and patients with right lateral lesions were compared to all other patients. The results show that all four standard Hayling Test clinical measures are sensitive to frontal lobe damage although only the suppression error and overall scores were specific to the frontal region. Although all frontal patients produced blatant suppression errors, a specific right lateral frontal effect was revealed for producing errors that were subtly wrong. In addition, frontal patients overall produced fewer correct responses indicative of developing an appropriate strategy but only the right lateral group showed a significant deficit. This problem in strategy attainment and implementation could explain, at least in part, the suppression error impairment. Contrary to previous studies there was no specific frontal effect for verbal initiation. Overall, our results support a role for the right lateral frontal region in verbal suppression and, for the first time, in strategy generation/use.

The grey matter correlates of impaired decision-making in multiple sclerosis.

OBJECTIVE: People with multiple sclerosis (MS) have difficulties with decision-making but it is unclear if this is due to changes in impulsivity, risk taking, deliberation or risk adjustment, and how this relates to brain pathology. METHODS: We assessed these aspects of decision-making in 105 people with MS and 43 healthy controls. We used a novel diffusion MRI method, diffusion orientational complexity (DOC), as an index of grey matter pathology in regions associated with decision-making and also measured grey matter tissue volumes and white matter lesion volumes. RESULTS: People with MS showed less adjustment to risk and slower decision-making than controls. Moreover, impaired decision-making correlated with reduced executive function, memory and processing speed. Decision-making impairments were most prevalent in people with secondary progressive MS. They were seen in patients with cognitive impairment and those without cognitive impairment. On diffusion MRI, people with MS showed DOC changes in all regions except the occipital cortex, relative to controls. Risk adjustment correlated with DOC in the hippocampi and deliberation time with DOC in the medial prefrontal, middle frontal gyrus, anterior cingulate and caudate parcellations and with white matter lesion volumes. CONCLUSIONS: These data clarify the features of decision-making deficits in MS, and provide the first evidence that they relate to grey and white matter abnormalities seen using MRI.

Limitations of the trail making test part-B in assessing frontal executive dysfunction.

Part B of the Trail Making Test (TMT-B) is one of the most widely used neuropsychological tests of "executive" function. A commonly held assumption is that the TMT-B can be used to detect frontal executive dysfunction. However, so far, research evidence has been limited and somewhat inconclusive. In this retrospective study, performance on the TMT-B of 55 patients with known focal frontal lesions, 27 patients with focal non-frontal lesions and 70 healthy controls was compared. Completion time and the number of errors made were examined. Patients with frontal and non-frontal lesions performed significantly worse than healthy controls for both completion time and the number of errors. However, there was no significant difference for both completion time and the number of errors when patients with frontal and non-frontal lesions were compared. Performance was also not significantly different between patients with focal lesions within different regions of the frontal lobe (orbital, left lateral, right lateral, medial). Our findings suggest that the TMT-B is a robust test for detection of brain dysfunction. However, its capacity for detecting frontal executive dysfunction appears rather limited. Clinicians should be cautious when drawing conclusions from performance on the TMT-B alone.

"My Mind Is Doing It All": No "Brake" to Stop Speech Generation in Jargon Aphasia.

OBJECTIVE: To study whether pressure of speech in jargon aphasia arises out of disturbances to core language or executive processes, or at the intersection of conceptual preparation. BACKGROUND: Conceptual preparation mechanisms for speech have not been well studied. Several mechanisms have been proposed for jargon aphasia, a fluent, well-articulated, logorrheic propositional speech that is almost incomprehensible. METHODS: We studied the vast quantity of jargon speech produced by patient J.A., who had suffered an infarct after the clipping of a middle cerebral artery aneurysm. We gave J.A. baseline cognitive tests and experimental word- and sentence-generation tasks that we had designed for patients with dynamic aphasia, a severely reduced but otherwise fairly normal propositional speech thought to result from deficits in conceptual preparation. RESULTS: J.A. had cognitive dysfunction, including executive difficulties, and a language profile characterized by poor repetition and naming in the context of relatively intact single-word comprehension. J.A.'s spontaneous speech was fluent but jargon. He had no difficulty generating sentences; in contrast to dynamic aphasia, his sentences were largely meaningless and not significantly affected by stimulus constraint level. CONCLUSIONS: This patient with jargon aphasia highlights that voluminous speech output can arise from disturbances of both language and executive functions. Our previous studies have identified three conceptual preparation mechanisms for speech: generation of novel thoughts, their sequencing, and selection. This study raises the possibility that a "brake" to stop message generation may be a fourth conceptual preparation mechanism behind the pressure of speech characteristic of jargon aphasia.

MRI-visible perivascular spaces: relationship to cognition and small vessel disease MRI markers in ischaemic stroke and TIA.

BACKGROUND: MRI-visible perivascular spaces (PVS) are potential neuroimaging markers of cerebral small vessel disease, but their functional significance and mechanisms remain uncertain. We investigated the association between PVS and cognitive impairment, and other MRI markers of small vessel disease, in a patient cohort of ischaemic stroke/transient ischaemic attack (TIA) referrals. METHODS: Data were collected from a prospective observational database. Standardised detailed neuropsychological testing was performed. A validated visual rating scale on T2-weighted MRI was used to categorise PVS severity; validated scales were used to assess white matter hyperintensities (WMH), cerebral microbleeds (CMB) and lacunes. RESULTS: We included 246 patients (45.1% female, mean age 62 years). No significant association between PVS severity grade in any brain region and impairment in any cognitive domain was identified. In multivariable analysis, WMH and hypertension (but not age) were independently associated with basal ganglia PVS severity (OR: 1.27; p<0.0001 and OR: 4.89; p=0.013, respectively). Increasing PVS severity in the basal ganglia was associated with lacunar stroke subtype (p<0.0001). Age and hypertension (but not WMH or lacunar stroke subtype) were independently associated with centrum semiovale PVS severity (OR: 1.19; p=0.013 and OR: 3.71; p=0.007, respectively). CONCLUSIONS: PVS do not have an independent association with cognitive impairment in patients with ischaemic stroke or TIA. The associations with clinical-radiological factors are consistent with the hypothesis that PVS reflect cerebral small vessel disease; the different associations for basal ganglia and centrum semiovale PVS might indicate different underlying small vessel arteriopathies according to PVS anatomical distribution, but this requires further study.

Cognitive dysfunction and depression in Fabry disease: a systematic review.

BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder, leads to multi-organ dysfunction, including cerebrovascular disease and psychological disorders. However, the prevalence and pattern of associated cognitive dysfunction is not well understood. OBJECTIVES: To investigate whether there is reliable evidence for neuropsychological impairment in patients with Fabry disease and which cognitive domains are affected. To estimate the prevalence of and factors associated with depression in patients with Fabry disease. METHOD: Qualitative systematic review of the literature of studies conducting neuropsychological assessment or measuring the prevalence of depression in adults with Fabry disease using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines where appropriate. RESULTS: There is some evidence for neuropsychological impairment in Fabry disease in executive functioning, information processing speed and attention, with preservation of: general intellectual functioning, memory, naming, perceptual functioning and global cognitive functioning. Prevalence rates of depression in Fabry disease ranged from 15% to 62%, with the largest study to date reporting a prevalence rate of 46%. The most common factor associated with depression was neuropathic pain, both directly and indirectly by affecting social and adaptive functioning. CONCLUSION: Our review suggests that Fabry disease may be associated with a characteristic pattern of cognitive deficits and a high prevalence of psychological disorders such as depression but highlights the limited available data. Exploring the nature of cognitive impairment in Fabry disease using standardised neuropsychological assessment, brain imaging and measures of depression is an important task for future research.