The pattern of cortical thickness associated with executive dysfunction in MCI and SCC: The MEMENTO cohort.

BACKGROUND: The association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC. METHODS: All participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n=1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer. RESULTS: The global executive function score was related to the BPF (sß: 0.091, P<0.001) and CT in the right supramarginal (sß: 0.060, P=0.041) and right isthmus cingulate (sß: 0.062, P=0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P<0.001) and CT in the left parsorbitalis region (sß: 0.045, P=0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P<0.001) and CT in the right supramarginal region (sß: 0.061, P=0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P=0.045) and CT in the right precuneus (sß: 0.073, P=0.019) and right isthmus cingulate region (sß: 0.054, P=0.032). CONCLUSIONS: In a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD.

Different clinical outcomes between cerebral amyloid angiopathy-related inflammation and non-inflammatory form.

OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1 years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3 pg/ml vs 490.8 pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). INTERPRETATION: CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.

Vascular cognitive impairment: Advances and trends.

The presence of vascular neurocognitive impairment (whatever the severity) is always associated with a functional impact and increased risk of dependency and institutionalization. However, vascular cognitive impairment remains underdiagnosed, and the mechanisms underlying post-stroke cognitive disorders are still poorly understood. However, the advent of new criteria and a standardized international neuropsychological battery is expected to lead to improved diagnosis and management, and the development of novel techniques (such as brain imaging and amyloid PET) should improve our understanding of the mechanisms underlying vascular cognitive impairment and help to identify potential targets for therapy.

Neuropsychological assessment and cerebral vascular disease: the new standards.

Vascular cognitive impairment (VCI) includes vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and mixed dementia. In clinical practice, VCI concerns patients referred for clinical stroke or cognitive complaint. To improve the characterization of VCI and to refine its diagnostic criteria, an international group has elaborated a new standardized evaluation battery of clinical, cognitive, behavioral and neuroradiological data which now constitutes the reference battery. The adaption of the battery for French-speaking subjects is reported as well as preliminary results of the on-going validation study of the GRECOG-VASC group [Clinical Trial NCT01339195]. The diagnostic accuracy of various screening tests is reviewed and showed an overall sub-optimal sensitivity (<0.8). Thus, the general recommendation is to perform systematically a comprehensive assessment in stroke patients at risk of VCI. Furthermore,the use of a structured interview has been shown to increase the detection of dementia. In addition to the well known NINDS-AIREN criteria of VaD, criteria of VCI have been recently proposed which are based on the demonstration of a cognitive disorder by neuropsychological testing and either history of clinical stroke or presence of vascular lesion by neuroimaging suggestive of a link between cognitive impairment and vascular disease. A memory deficit is no longer required for the diagnosis of VaD as it is based on the cognitive decline concerning two or more domains that affect activities of daily living. Both VaMCI and VaD are classified as probable or possible. These new criteria have yet to be validated. Considerable uncertainties remain regarding the determinant of VCI, and especially the lesion amount inducing VCI and VaD. The interaction between lesion amount and its location is currently re-examined using recent techniques for the analysis of MRI data. The high frequency of associated Alzheimer pathology is now assessable in vivo using amyloid imaging. The first studies showed that about a third of patients with VaD due to small vessel disease or with poststroke dementia have amyloid PET imaging suggestive of AD. These new techniques will examine the interaction between vascular lesions and promotion of amyloid deposition. Although results of these on-going studies will be available in few years, these data indicate that efforts should be done in clinical practice to reduce underdiagnosis of VCI; VCI should be examined using a specific protocol which will be fully normalized soon for French-speaking patients; the sub-optimal sensitivity of screening tests prompts to use a structured interview to grade Rankin scale and to perform systematically a comprehensive assessment in stroke patients at risk of VCI; poststroke dementia occurring after 3 months poststroke may be preventable by treatment of modifiable vascular risk factors and secondary prevention of stroke recurrence according to recent recommendations.

[A comparison of stroke patients' characteristics between a sub-Saharan Africa population (Abidjan) and a French stroke unit (Amiens): An observational study]. / Comparaison des caractéristiques cliniques et de la prise en charge des accidents vasculaires cérébraux entre une population africaine (Abidjan) et une population française (Amiens) : une étude observationnelle.

INTRODUCTION: Stroke characteristics in Sub-Saharan Africa (SSA) differ from developed countries. However, SSA subjects undergo epidemiological and demographic transition and it appears that the prevalence of vascular risk factors (RF) increases in this population. Here we aimed to compare stroke patients' characteristics between a SSA hospital (Cocody University Hospital, Abidjan, Côte d'Ivoire) and a French stroke unit (Amiens University Hospital, Amiens, France). METHODS: This retrospective study included all consecutive stroke patients admitted between January and May 2008 (Cocody University Hospital, Abidjan, Côte d'Ivoire) and between October and December 2008 (Amiens University Hospital, Amiens, France). We assessed each patient's demographic details, RF, and CT confirmed pathological stroke type. The glomerular filtration rate (GFR) was estimated using the four-component Modification of Diet in Renal Disease (MDRD) equation and CKD was defined as a GFR less than 60ml/min/1.73 m(2). RESULTS: One hundred and ninety five patients were included (Amiens: 92; Abidjan: 103) with a mean age of 63±14 years. Patients in Amiens had more known vascular RF than African patients, whereas African patients had more RF discovered during hospitalisation. Furthermore, CKD was significantly more common in SSA patients (43% vs 24%, P=0.001). More African than European patients had cerebral hemorrhage (34% vs 8%, P<0.001) but acute stroke mortality and treatments at hospital discharge were similar between the two hospitals. Finally, a high proportion of patients in Abidjan suffered from cervical atherosclerosis, although it was significantly lower than patients in Amiens (37% vs 67%, P<0.001). CONCLUSION: Although this was a hospital-based study, CKD appears to be very common in SSA acute stroke patients. These findings could partly explain the high prevalence of cervical atherosclerosis found in this population. These results warrant confirmation in prospective studies.

Predictors of newly diagnosed atrial fibrillation in cryptogenic stroke: a cohort study.

BACKGROUND AND PURPOSE: A significant proportion of cryptogenic ischaemic strokes are due to paroxysmal atrial fibrillation (AF). As paroxysmal AF appears to inexorably progress to persistent or permanent AF, this study with long-term follow-up was designed to establish the profile of patients who developed AF after hospital discharge. METHODS: All patients with cryptogenic ischaemic stroke over a 1-year period were included (n = 164). Patients were prospectively followed up at the outpatient clinic. Information on long-term outcome included the presence of newly diagnosed AF (NDAF). A specific NDAF assessment was performed at least 2 years after the index stroke using a structured telephone interview. Baseline clinical, laboratory, and echocardiographic data of these patients were retrospectively recorded. Independent predictive factors were then used to produce a predictive grading score for NDAF, derived by logistic regression analysis. RESULTS: With a median follow-up of 854 days, 22 cases of NDAF (13%) were observed. On multivariate analysis, factors associated with NDAF were age ≥72 years (two points), history of coronary artery disease (one point) or stroke (one point), and left atrial area ≥16 cm(2) (two points) (total score ranging from 0 to 6). Patients with a score ≤1 point did not have NDAF during follow-up. CONCLUSIONS: In cryptogenic ischaemic stroke, the NDAF score can be used to target patients at high risk of developing AF after hospital discharge, as a score of 0-1 was highly predictive of the absence of NDAF during follow-up. These results need to be confirmed in prospective studies.

Alertness in young healthy subjects: an fMRI study of brain region interactivity enhanced by a warning signal.

An effective connectivity study was carried out on 16 young, healthy subjects performing an alertness task. The objective of this study was to develop and to evaluate a putative network model of alertness by adapting structural equation modeling to fMRI data. This study was designed to evaluate the directed interactivity of an attentional network during intrinsic and phasic alerting tasks. On the basis of theoretical hypotheses, clinical observations, behavioral data and neuroimaging studies, it was hypothesized that neural circuits in the right hemisphere including the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, inferior parietal cortex and the thalamus were involved. The results of this study support the existence of a common network of activated areas with significant path coefficient differences between intrinsic and phasic alertness. Functional interactivity was significantly reinforced during the phasic alertness task and appeared to preferentially involve activity in the DLPFC region, whereas the path coefficients of the model were well-balanced during intrinsic alertness. This study highlights the predominant role of the DLPFC region in maintenance of a state of alertness and in temporal preparation during an alertness task.

Anatomy of executive deficit following ruptured anterior communicating artery aneurysm.

BACKGROUND AND PURPOSE: To evaluate behavioral and cognitive deficits following anterior communicating artery aneurysm rupture and determine critical lesion locations. METHODS: We investigated 74 patients with standardized cognitive tests and behavioral inventory. Two examiners rated MRI signal abnormalities in 51 predetermined regions of interest. Classification tree analysis was used to select regions associated with each cognitive deficit. RESULTS: Eleven patients presented behavioral executive deficits and 10 had cognitive executive deficit. Their presence depended on left hemisphere lesions only: (i) ventral striatum lesion was associated with behavioral executive deficit (P = 0.04), reduction of activities (P = 0.01), and hyperactivity (P = 0.02); (ii) superior frontal gyrus lesion, with cognitive executive deficit (P = 0.01), action initiation deficit (P = 0.02), and rule deduction deficit (P = 0.02); (iii) anterior half of centrum semiovale lesion, with Stroop inhibition deficit (P = 0.02); (iv) medial superior and middle frontal gyri lesions, with task coordination deficit (P = 0.01); and (v) middle frontal gyrus lesion, with words generation deficit (P = 0.02). CONCLUSION: This study supports that (i) cognitive executive deficits depend mostly on lateral prefrontal lesions, (ii) with locations varying according to executive process, and (iii) behavioral executive deficits are mainly due to left ventral striatum lesion in post-aneurysmal damage.

Deficit of episodic memory: anatomy and related patterns in stroke patients.

BACKGROUND/AIMS: Despite numerous studies performed in selected populations, major uncertainties regarding the anatomy and patterns of episodic memory deficit still persist. Such objectives require the analysis of consecutive unselected patients with well-delimitated lesions and the use of specific methodology. METHODS: Nonaphasic stroke patients (n = 73) referred for cognitive complaints or deficits were examined using a standardized neuropsychological battery. Verbal episodic memory was assessed by the Grober and Buschke test. RESULTS: Episodic memory deficit was related to lesions of medial temporal, thalamic, frontal, lenticular, and centrum semiovale regions, with a left hemisphere predominance. Although not specific, an immediate recall deficit was frequently observed in thalamic lesions (OR: 5.2, 95% CI: 1.09-24.9). False recognitions (OR: 25.7, 95% CI: 2.7-249) and efficiency of cued recall (OR: 8.6, 95% CI: 1.3-57) were highly specific of frontal damage. When combined with the usual 'frontal lobe' tests, this pattern of memory disorder was an independent predictor (OR: 36, 95% CI: 4.3-302) and increased the sensitivity of diagnosis of frontal damage (sensitivity: 0.92, specificity: 0.89). CONCLUSIONS: This study extends the classical anatomy of episodic verbal memory. In addition, the 'frontal memory pattern' was found to be relatively specific and to be an independent predictor of frontal damage.

Phase-contrast MR imaging support for the diagnosis of aqueductal stenosis.

BACKGROUND AND PURPOSE: Patients with aqueductal stenosis (AS) present with various clinical and radiologic features. Conventional MR imaging provides useful information in AS but depends on a subjective evaluation by the neuroradiologist. The purpose of this study was to evaluate the support of the phase-contrast MR imaging (PC-MR imaging) technique (sensitive to CSF flows) for the diagnosis of AS. MATERIALS AND METHODS: We retrospectively considered 17 patients who underwent PC-MR imaging to explore hydrocephalus, with the absence of CSF flow at the aqueductal level. We analyzed their clinical and morphologic MR imaging data. RESULTS: None of the usually reported direct or indirect signs of aqueductal obstruction were seen in 7 patients in whom the clinical suggestion of AS was confirmed by PC-MR imaging results. Seven patients in this population had a third ventriculostomy, and 5 of them were among those in whom conventional MR imaging failed to reveal signs of aqueductal obstruction. All of these 7 patients had a positive postsurgical outcomes. The analysis of CSF and vascular dynamic data in this population was compared with an aged-matched population, and these data were found similar except for the fourth ventricular CSF flush flow latency. CONCLUSIONS: PC-MR imaging supports the diagnosis of CSF flow blockage at the aqueductal level in a reliable, reproducible, and rapid way, which aids in the diagnosis of AS in patients with clinical and/or radiologic suggestion of obstructive hydrocephalus. We, therefore, suggest using this technique in the current evaluation of hydrocephalus.

[Frontal lobe, executive functions and cognitive control]. / Lobe frontal, fonctions exécutives et controle cognitif.

The approach of executive functions began with the early description of behavioural disorders induced by frontal damage. The development of neuropsychology has led to the description of a large variety of cognitive disorders. The interpretation in cognitive terms of these disorders has emphasized the critical impairment of executive functions which are involved in non-routine situations. The role of working memory, initially suggested by animal studies, has also largely influenced theoretical approaches. Numerous studies have been interpreted within the theoretical frameworks developed by Shallice and by Baddeley. A large amount of studies have allowed the specification of control processes (initiation, inhibition...). Recent studies are beginning to investigate cognitive disorders underlying behavioural changes such as deficits of emotional, social and metacognitive processes. In addition these studies seriously question the assumption of a unique central control system. These studies have deeply influenced the clinical approach, the assessment and the diagnosis of executive syndrome. For clinical practice, these data lead to favour specific assessment of some key behavioural and cognitive deficits based on a battery of tests and structured interview of an informant.