Functional connectivity variations in mild cognitive impairment: associations with cognitive function

Participants with mild cognitive impairment (MCI) have a higher likelihood of developing Alzheimer's disease (AD) compared to those without MCI, and functional magnetic resonance neuroimaging (fMRI) used with MCI participants may prove to be an important tool in identifying early biomarkers for AD. We tested the hypothesis that functional connectivity differences exist between older adults with and without MCI using resting-state fMRI. Data were collected on over 200 participants of the Rush Memory and Aging Project, a community-based, clinical-pathological cohort study of aging. From the cohort, 40 participants were identified as having MCI, and were compared to 40 demographically matched participants without cognitive impairment. MCI participants showed lesser functional connectivity between the posterior cingulate cortex and right and left orbital frontal, right middle frontal, left putamen, right caudate, left superior temporal, and right posterior cingulate regions; and greater connectivity with right inferior frontal, left fusiform, left rectal, and left precentral regions. Furthermore, in an alternate sample of 113, connectivity values in regions of difference correlated with episodic memory and processing speed. Results suggest functional connectivity values in regions of difference are associated with cognitive function and may reflect the presence of AD pathology and increased risk of developing clinical AD.     

Microstructural and functional MRI studies of cognitive impairment in epilepsy

Cognitive impairment is the most common comorbidity in children with epilepsy, but its pathophysiology and predisposing conditions remain unknown. Clinical epilepsy characteristics are not conclusive in determining cognitive outcome. Because many children with epilepsy do not have macrostructural magnetic resonance imaging (MRI) abnormalities, the underlying substrate for cognitive impairment may be found at the microstructural or functional level. In the last two decades, new MRI techniques have been developed that have the potential to visualize microstructural or functional abnormalities associated with cognitive impairment. These include volumetric MRI, voxel‐based morphometry (VBM), diffusion tensor imaging (DTI), MR spectroscopy (MRS), and functional MRI (fMRI). All of these techniques have shed new light on various aspects associated with, or underlying, cognitive impairment, although their use in epilepsy has been limited and focused mostly on adults. Therefore, in this review, the use of all these different MRI techniques to unravel cognitive impairment in epilepsy is discussed both in adults and children with epilepsy. Volumetric MRI and VBM have revealed significant volume losses in the area of the seizure focus as well as in distant areas. DTI adds evidence of loss of integrity of connections from the seizure focus to distant areas as well as between distant areas. MRS and fMRI have shown impaired function both in the area of the seizure focus as well as in distant structures. For this review we have compiled and compared findings from the various techniques to conclude that cognitive impairment in epilepsy results from a network disorder in which the (micro)structures as well as the functionality can be disturbed.     

Subjective cognitive impairment: Functional MRI during a divided attention task

Background

Individuals with subjective cognitive impairment (SCI) have persistent memory complaints but normal neurocognitive performance. For some, this may represent a pre-mild cognitive impairment (MCI) stage of Alzheimer's disease (AD). Given that attentional deficits and associated brain activation changes are present early in the course of AD, we aimed to determine whether SCI is associated with brain activation changes during attentional processing.

Methods

Eleven SCI subjects and 10 controls completed a divided attention task during functional magnetic resonance imaging.

Results

SCI and control groups did not differ in sociodemographic, neurocognitive or behavioural measures. When group activation during the divided attention task was compared, the SCI group demonstrated increased activation in left medial temporal lobe, bilateral thalamus, posterior cingulate and caudate.

Conclusion

This pattern of increased activation is similar to the pattern of decreased activation reported during divided attention in AD and may indicate compensatory changes. These findings suggest the presence of early functional changes in SCI; longitudinal studies will help to further elucidate the relationship between SCI and AD.     

Functional MRI in children with epilepsy

Advances in brain mapping with functional magnetic resonance imaging (fMRI) have opened an important window into understanding how language is organized in the developing brain. Children with epilepsy, particularly those anticipating surgical intervention, may benefit from preoperative language localization with fMRI, thus minimizing the risk of incurring new deficits. Clinical applications of fMRI, however, await more information on how different linguistic skills are represented in the developing brain and how epileptic lesions impact on this organization at different stages of cognitive development. This article presents some of the current methods for brain mapping in children as well as early results using fMRI for language mapping in pediatric epilepsy. Copyright Copyright 1999 S. Karger AG, Basel     

Reduced mismatch negativity in mild cognitive impairment: associations with neuropsychological performance

Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p < 0.01). Reduced right temporal MMN was significantly associated with poorer verbal learning (r = 0.496; p < 0.01) and reduced left temporal MMN was significantly associated with increased self-reported disability (r = -0.419; p < 0.05). These results indicate that patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.     

血管性认知障碍不同亚型患者认知功能及MRI检查的对比研究

目的探讨血管性认知障碍各亚型患者之间及其与认知功能正常者之间的认知功能及脑组织影像学表现的差异。方法采用简易智能状态检查量表、认知能力筛查量表和简易智能-认知能力联合检查量表对62例血管性认知障碍患者(无痴呆型血管性认知障碍34例、血管性痴呆18例、混合性痴呆10例)和50例正常对照者的认知功能进行评价,通过磁共振成像分析其容积测量值、脑叶萎缩、皮质下白质疏松和腔隙性脑梗死等影像学参数的差异。结果与对照组比较,血管性认知障碍各亚组患者认知功能评分呈逐步递减趋势(均P<0.05),但血管性痴呆与混合性痴呆患者之间差异无统计学意义(P>0.05)。血管性认知障碍各亚组患者双侧前额角容积、第三脑室容积测量值以及额叶、颞叶、顶叶、枕叶萎缩,皮质下白质疏松和腔隙性脑梗死评分均高于对照组(P<0.05),其影像学异常改变在进展为痴呆后更为明显。混合性痴呆患者的特征性表现为双侧海马容积、内嗅叶皮质容积减小,颞叶萎缩(均P<0.05),但无明显的腔隙性脑梗死(P>0.05)。结论血管性认知障碍患者的影像学异常改变可部分反映不同亚型的病理改变,但对认知障碍程度的反映尚缺乏敏感性,能否联合认知功能评分共同作为血管性认知障碍临床预测指标尚待进一步研究。     

局灶性癫痫患者认知障碍的相关性分析

目的 通过神经心理评估探究局灶性癫痫患者可能产生认知障碍的相关因素.方法 收集2016年3月-2020年1月于天津医科大学总医院门诊及住院的癫痫病患者53例,其中男25例,女28例,平均年龄(23.58±13.24)岁,平均病程(6.49±7.39)年,均符合2017年国际抗癫痫联盟(ILEA)局灶性癫痫的诊断标准,无...     

Functional MRI applications in epilepsy surgery

Functional magnetic resonance imaging (fMRI) is a non-invasive neuroimaging technique that has grown rapidly in popularity over the past decade. It is already prevalent in psychology, cognitive and basic neuroscience research and is being used increasingly as a tool for clinical decision-making in epilepsy. It has been used to determine language location and laterality in patients, sometimes eliminating the need for invasive tests. fMRI can been used pre-surgically to guide resection margins, preserving eloquent cortex. Other fMRI paradigms assessing memory, visual and somatosensory systems have limited clinical applications currently, but show great promise. Simultaneous recording of electroencephalogram (EEG) and fMRI has also provided insights into the networks underlying seizure generation and is increasingly being used in epilepsy centres. In this review, we present some of the current clinical applications for fMRI in the pre-surgical assessment of epilepsy patients, and examine a number of new techniques that may soon become clinically relevant.     

Functional impairment in the diagnosis of mild cognitive impairment

The criterion on functional activity in the revised diagnostic criteria for mild cognitive impairment (MCI) seems to be conceptually and operationally problematic.We investigated the predictive validity for dementia of this criterion in 140 patients with MCI who participated in the baseline study of the Korean Longitudinal Study on Health and Aging and completed 18-month follow-up evaluation (mean duration of follow-up, 1.57±0.24 y). Annual conversion rates to dementia were compared between the patients who fulfilled the criterion on functional activity and those who did not. Annual conversion rates to dementia of the patients who fulfilled the criterion on functional activity was 4.76%, whereas that of the patients with MCI who did not was 33.07%, indicating that the criterion on functional activity was a significant negative predictor of dementia (odds ratio=0.12). Re-revision of the criterion on functional activity may be warranted to solve its conceptual and operational ambiguities.     

MRI and cognitive impairment in Parkinson's disease

Patients with Parkinson's disease (PD) may present impairment in cognitive functions even at early stages of the disease. When compared with the general population, their risk of dementia is five to six times higher. Recent investigations using structural MRI have shown that dementia in PD is related to cortical structural changes and that specific cognitive dysfunctions can be attributed to atrophy in specific structures. We review the structural MRI studies carried out in PD using either a manual region of interest (ROI) approach or voxel‐based morphometry (VBM). ROI studies have shown that hippocampal volume is decreased in patients with PD with and without dementia; in addition, hippocampal atrophy correlated with deficits in verbal memory. VBM studies have demonstrated that dementia in PD involves structural changes in limbic areas and widespread cortical atrophy. Findings in nondemented patients with PD are less conclusive, possibly because cognitively heterogeneous groups of patients have been studied. Patients with PD with cognitive impairment and/or visual hallucinations present greater brain atrophy than patients without these characteristics. These findings suggest that cortical atrophy is related to cognitive dysfunction in PD and precedes the development of dementia. Structural MRI might therefore provide an early marker for dementia in PD. © 2009 Movement Disorder Society     

Catechol-O-methyltransferase Val158Met polymorphism in schizophrenia: associations with cognitive and motor impairment

Cognitive and motor deficits have been proposed as markers of abnormal neurodevelopment in schizophrenia and have been associated with genetic liability. In a multicenter study involving 106 subjects, 56 with deficit schizophrenia and 50 with nondeficit schizophrenia, we tested the hypothesis that the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism is associated with cognitive and motor deficits either in schizophrenia as a whole or in its deficit subtype. The COMT Val(158)Met polymorphism shared 6.6% of the executive/attention dysfunction variance in patients with schizophrenia and 15.6% of the motor impairment variance in patients with deficit schizophrenia. These results support the hypothesis that the COMT Val(158)Met polymorphism influences executive functions in schizophrenia and the neuromotor performance in the deficit subtype only.     

Functional deficits in patients with mild cognitive impairment: prediction of AD

OBJECTIVE: To evaluate the predictive utility of self-reported and informant-reported functional deficits in patients with mild cognitive impairment (MCI) for the follow-up diagnosis of probable AD. METHODS: The Pfeffer Functional Activities Questionnaire (FAQ) and Lawton Instrumental Activities of Daily Living (IADL) Scale were administered at baseline. Patients were followed at 6-month intervals, and matched normal control subjects (NC) were followed annually. RESULTS: Self-reported deficits were higher for patients with MCI than for NC. At baseline, self- and informant-reported functional deficits were significantly greater for patients who converted to AD on follow-up evaluation than for patients who did not convert, even after controlling for age, education, and modified Mini-Mental State Examination scores. While converters showed significantly more informant- than self-reported deficits at baseline, nonconverters showed the reverse pattern. Survival analyses further revealed that informant-reported deficits (but not self-reported deficits) and a discrepancy score indicating greater informant- than self-reported functional deficits significantly predicted the development of AD. The discrepancy index showed high specificity and sensitivity for progression to AD within 2 years. CONCLUSIONS: These findings indicate that in patients with MCI, the patient's lack of awareness of functional deficits identified by informants strongly predicts a future diagnosis of AD. If replicated, these findings suggest that clinicians evaluating MCI patients should obtain both self-reports and informant reports of functional deficits to help in prediction of long-term outcome.     

Older adults with epilepsy demonstrate cognitive impairments compared with patients with amnestic mild cognitive impairment

Little is known about the cognitive effects of chronic epilepsy in older adults. To better characterize cognitive impairment in seniors with epilepsy, we compared cognitive performance of 26 seniors with epilepsy with that of 26 well-matched patients with mild cognitive impairment (MCI) and 26 well-matched healthy older adults. Participants completed neuropsychological testing with the Dementia Rating Scale (DRS), Logical Memory, and CFL Word Fluency. There were no significant demographic group differences, although seniors with epilepsy had higher self-reported depression. Seniors with epilepsy performed below controls on virtually all neuropsychological tests, and performed below patients with MCI on DRS Total score, Initiation/Perseveration, and CFL Fluency. Seniors with epilepsy on antiepileptic drug (AED) polytherapy had the most severe cognitive deficits, whereas seniors with epilepsy on AED monotherapy were comparable to cholinesterase inhibitor-na?ve patients with MCI. This study emphasizes the clinical importance of cognitive impairment in seniors with epilepsy and highlights the need for future studies addressing causes and treatment of cognitive impairment.     

A role for sleep disruption in cognitive impairment in children with epilepsy

Early-onset epilepsy is associated with a poor cognitive outcome, with the cumulative burden of both ictal and interictal epileptiform discharges likely to contribute significantly. Memory consolidation has been shown to occur during sleep in healthy children, with an associated electroencephalographic signature. This may be disrupted in children with epilepsy, who exhibit a high incidence of sleep disorders, whether directly related to their seizures or as a comorbidity. Conversely, seizure semiology may be influenced by sleep. In this review we present clinical and experimental evidence that suggests that the disruption of sleep architecture by epileptiform discharges may be an important factor contributing to cognitive impairment in children with epilepsy.     

Structural MRI correlates of cognitive impairment in patients with multiple sclerosis

In a multicenter setting, we applied voxel‐based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal‐appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing‐remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel‐wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty‐three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive‐relevant WM tracts followed by atrophy of cognitive‐relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel‐wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. Hum Brain Mapp 37:1627‐1644, 2016. © 2016 Wiley Periodicals, Inc.