Medial temporal lobe atrophy in memory disorders

Medial temporal lobe atrophy determined by temporal lobe oriented computed tomography (CT), 1 year before death, is strongly associated with histopathologically confirmed Alzheimer’s disease (AD). The aim of this study was to assess the diagnostic accuracy of medial temporal lobe measurement for the diagnosis of AD in patients referred to a memory disorders clinic, especially those at an early stage of the disease. CT oriented to the temporal lobe was performed in 333 subjects aged 41–93 years consecutively recruited in a Memory Disorders Clinic: 124 had probable AD, Mini Mental State score (MMS) = 17 (8); 50 possible AD [MMS = 21 (5)]; and 119 patients had miscellaneous memory disorders [MMS = 22 (7): frontotemporal lobe dementia, subcortical dementia, cortical Lewy body disease, vascular dementia, Korsakoff syndrome, focal atrophy, etc.]. There were also 19 anxious/ depressed patients [MMS = 29 (1)] with normal performance on memory tests, and 21 controls. The minimum width of the medial temporal lobe was measured. The best cut-off to distinguish AD patients from non-AD patients was 11.5 mm, in agreement with data in the literature. At this threshold, 84% of probable AD patients had a positive test and 90% of controls and anxious/depressed patients had a negative test. For the diagnosis of probable AD, sensitivity of the measurement was 0.81, specificity 0.95, predictive positive value 0.99, predictive negative value 0.45, and diagnostic accuracy 0.83. The test was positive in half the possible AD patients, and half those with miscellaneous memory disorders. It was negative in all anxious/depressed patients. Therefore, temporal lobe oriented CT might be a valuable tool for assessment of medial temporal lobe atrophy in AD routine practice. Received: 27 September 1995 Accepted: 10 October 1996     

Frontal atrophy as a marker for dementia conversion in Parkinson's disease with mild cognitive impairment

This study aimed to investigate the cortical neural correlates of dementia conversion in Parkinson's disease with mild cognitive impairment (PD‐MCI). We classified 112 patients with drug‐naïve early stage PD meeting criteria for PD‐MCI into either PD with dementia (PDD) converters (n = 34) or nonconverters (n = 78), depending on whether they developed dementia within 4 years of PD diagnosis. Cortical thickness analyses were performed in 34 PDD converters and 34 matched nonconverters. Additionally, a linear discriminant analysis was performed to distinguish PDD converters from nonconverters using cortical thickness of the regions that differed between the two groups. The PDD converters had higher frequencies of multiple domain MCI and amnestic MCI with storage failure, and poorer cognitive performances on frontal/executive, memory, and language function domains than did the nonconverters. Cortical thinning extending from the posterior cortical area into the frontal region was observed in PDD converters relative to nonconverters. The discriminant analysis showed that the prediction model with two cortical thickness variables in the right medial superior frontal and left olfactory cortices optimally distinguished PDD converters from nonconverters. Our data suggest that cortical thinning in the frontal areas including the olfactory cortex is a marker for early dementia conversion in PD‐MCI.     

自然人群中老年人轻度认知障碍的随访研究

目的　研究自然人群中老年人轻度认知障碍 (MCI)向痴呆和阿尔茨海默病 (AD)的转化率。方法　以北京市 1997年痴呆患病率调查的样本人群为研究对象 ,对患病率调查时经简易智能状态检查法筛查、标准化神经心理测试和临床评估后诊断为MCI以及认知正常的受试者进行随访。比较MCI和认知正常受试者转化为痴呆和AD的转化率。结果　 12 1例MCI和 2 81名认知正常受试者平均随访大约 3年。MCI向痴呆和AD的平均年转化率分别为 14 1·10 0 -1·年-1和 8 0·10 0 -1·年 -1。认知正常受试者向痴呆和AD的平均年转化率分别为 1 6·10 0 -1·年 -1和 1 1·10 0 -1·年 -1。MCI转化为痴呆或AD的相对危险性分别为认知正常者的 9倍和 6倍。结论　MCI转化为痴呆的危险性远远大于认知正常的受试者。在未来开展痴呆人群综合防治的研究中 ,MCI是值得高度重视的人群。     

Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment

Background

The diagnosis of mild cognitive impairment (MCI) is clinically unhelpful, as many patients with MCI develop dementia but many do not.

Objective

To identify clinical instruments easily applicable in the clinical routine that might be useful to predict progression to dementia in patients with MCI assessed in the outpatient facility of a memory clinic.

Participants and methods

52 dementia‐free patients (mean (standard deviation) age 70 (6) years; 56% women) with MCI, and 65 healthy controls (age 69 (6) years; 54% women) underwent brain magnetic resonance scan with standardised visual assessment of medial temporal atrophy (MTA) and subcortical cerebrovascular lesions (SVLs). Follow‐up assessment occurred 15.4 (SD 3.4) months after baseline to detect incident dementia and improvement, defined as normal neuropsychological performance on follow‐up.

Results

Patients were classified into three groups according to the presence of memory disturbance only (MCI Mem), other neuropsychological deficits (MCI Oth) or both (MCI Mem+). MCI Mem and Mem+ showed MTA more frequently (31% and 47% v 5% and 14% of controls and MCI Oth, p<0.001). 11 patients developed dementia (annual rate 16.5%) and 7 improved on follow‐up. The only independent predictor of progression was MTA (odds ratio (OR) 7.1, 95% confidence interval (CI) 1.4 to 35.0), whereas predictors of improvement were the absence of memory impairment (OR 18.5, 95% CI 2.0 to 171.3) and normal MRI scan (OR 10.0, 95% CI 1.7 to 60.2).

Conclusion

Neuropsychological patterns identify groups of patients with MCI showing specific clinical features and risk of progression to dementia. MTA clinically rated with a visual scale is the most relevant predictor of progression and improvement.The concept of mild cognitive impairment (MCI) was originally coined by Petersen et al¹ to capture the preclinical stages of Alzheimer''s dementia. It is known that the formation of the neuropathological lesions of Alzheimer''s disease occurs decades before the first clinical symptoms.² Memory impairment is typically the initial presentation of Alzheimer''s disease, suggesting that memory disturbance in elderly people may be a sign of the transition phase between normal ageing and Alzheimer''s disease.¹ However, not all patients with MCI deteriorate.³ Available data suggest that the likelihood of a patient with MCI developing Alzheimer''s disease in the long term is around 50%, thus making the diagnosis of MCI in itself clinically unhelpful.⁴Pathological and clinical data indicate that some indicators of Alzheimer''s disease might be used to distinguish those patients with MCI who will progress from those who will not. Some of these indicators, such as hippocampal volumetry,⁵ τ and aβ proteins in the cerebrospinal fluid,⁶ and functional defects in the temporoparietal and posterior cingulate cortex,⁷ require technologically advanced tools and specific competences and are applicable only in specialised centres. Other markers of progression have been proposed, such as the involvement of multiple cognitive domains besides memory,⁸ or medial temporal lobe atrophy (MTA) on magnetic resonance imaging (MRI).⁹ These are more easily assessed in a non‐specialised clinical setting and could be implemented in second level centres.Our study aimed to identify clinical instruments, easily applicable in the clinical routine, that might be useful to predict progression to dementia in patients with MCI.     

Biomarkers for dementia and mild cognitive impairment in Parkinson's disease

Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well‐established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin‐like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society     

轻度认知损害海马萎缩的磁共振研究

目的　探讨轻度认知损害 (MCI)海马体积变化的特点。方法　对 16例健康老年人 (对照组 )、 15例MCI和 17例 Alzheimer病 (AD)患者行核磁共振 (MRI)、简易智力状态检查 (MMSE) ,经标准化处理和年龄性别修正后比较海马体积变化及其与 MMSE评分的相关性。结果　 MCI组 (6 0 79± 187mm3)、AD组 (5 12 4± 185 mm3)较对照组 (70 6 2± 2 0 4 mm3)的海马体积显著减少 ,萎缩程度分别为 14 % (P<0 .0 1)、2 7% (P<0 .0 0 1) ;AD组的海马体积较 MCI组显著萎缩 (P<0 .0 1) ,3组人群合并后 ,全体研究对象的海马体积与 MMSE评分呈显著正相关 (r=0 .8,P<0 .0 0 1) ,对照组 (r=0 .2 5 ,P>0 .0 5 )和 MCI组 (r=0 .33,P>0 .0 5 )不存在相关性。结论　海马体积萎缩有助于 MCI的诊断 ,可进一步监测其变化以判断转归     

脑白质疏松症与Binswanger病认知功能障碍的对比研究

目的探讨轻度认知功能障碍与痴呆在单纯脑白质疏松症(LA)、Binswanger病(BD)及脑白质疏松症合并脑梗死(LA CI)中的临床诊断价值.方法单纯LA组27例,BD组33例,LA CI组31例,对照组30例,行简易精神状态量表(MMSE)、临床记忆量表测验(CMS)、轻度认知功能障碍的认知评定并对比分析.结果单纯LA组、BD组、LA CI组MMSE及CMS成绩均明显低于对照组,差异有显著意义(P＜0.05);单纯LA组MMSE及CMS成绩明显高于BD组、LA CI组,差异有显著意义(P＜0.05);单纯LA组认知损害以轻度认知功能障碍为主(77.8%),无1例痴呆;BD组中度认知功能障碍占24.2%,痴呆占75.8%;LA CI组以中度认知功能障碍(19.4%)和痴呆(77.4%)为主.结论轻度认知功能障碍是诊断单纯LA的临床参考指标.中度认知功能障碍和痴呆是诊断BD和LA CI的临床参考指标.     

Medial temporal lobe function and structure in mild cognitive impairment

Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline.     

Progression to vascular dementia of patients with mild cognitive impairment: relevance of mild parkinsonian signs

Mild parkinsonian signs (MPS) may be found among patients presenting with mild cognitive impairment (MCI), but few data are available about the relation of these signs with the prospective risk for dementia. Our retrospective investigation considered a case-series of 119 MCI subjects followed over a three-year period: their baseline clinical picture has been analyzed in search of correlation between the cognito-motor profile and the final diagnosis. The population included 66 patients with amnesic MCI and 53 with an involvement of other cognitive areas (nonamnesic MCI). MPS were detected in 22 subjects (18.5%). At the first observation, MPS cases showed an higher frequency of nonamnesic MCI and more pronounced deficits at the Trail Making Test (p < 0.05). After a three-year follow-up, 48 patients had converted to dementia. The presence of MPS at the baseline evaluation was significantly related to the development of a vascular-type dementia. The study investigates the association between MPS and MCI and might indicate for these cases a greater risk for an involvement of executive functions and the subsequent development of vascular dementia.     

两种遗忘型轻度认知损害患者的随访比较

目的 比较单纯遗忘型轻度认知功能损害(aMCI-s)和多个认知领域损害遗忘型轻度认知功能损害(aMCI-m)患者的2年随访转归结果并分析其神经心理学变化.方法 采用MMSE、听觉词语学习测验(AVLT)、逻辑回忆测验(LMT)、连线测验(TMT)、Stroop色词测验(CWT)、Rey复杂图形测验(CFT)、五点连线测验(FPT)、画钟测验(CDT)、言语流畅性测验(VF)和临床痴呆量表(CDR)等一系列神经心理测验评估记忆障碍门诊130例遗忘型轻度认知功能损害(aMCI)就诊者(其中aMCI-s 66例和aMCI-m 64例),并进行平均2年的随访,MCI及AD的诊断标准分别参照美国Petersen等及美国神经病学、语言障碍和卒中-老年性痴呆和相关疾病学会(NINCDS-ADRDA)有关诊断标准.结果 aMCI的阿尔茨海默病(AD)总转化率为33.8%(44/130);aMCI-s和aMCI-m的AD转化率分别为26.2%(17/65)和42.9%(27/63),差异有统计学意义(x2=3.957,P=0.047).随着aMCI发展为AD,aMCI-s和aMCI-m组在记忆和执行功能方面的减退幅度接近,aMCI-s组的视空间结构能力相对保留,语言和注意力的减退更快,aMCI-m组的视空间结构能力衰退更为显著.结论 aMCI-m比aMCI-s更容易发展为AD,aMCI分为aMCI-s和aMCI-m对判断认知功能减退的速度是有必要的,有助于判断预后.     

Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer's disease: insights from functional MRI studies

Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have begun to reveal abnormalities in memory circuit function in humans suffering from memory disorders. Since the medial temporal lobe (MTL) memory system is a site of very early pathology in AD, a number of studies, reviewed here, have focused on this region of the brain. By the time individuals are diagnosed clinically with AD dementia, the substantial memory impairments appear to be associated with not only MTL atrophy but also hypoactivation during memory task performance. Prior to dementia, when individuals are beginning to manifest signs and symptoms of memory impairment, the hippocampal formation and other components of the MTL memory system exhibit substantial functional abnormalities during memory task performance. It appears that, early in the course of MCI when memory deficits and hippocampal atrophy are less prominent, there may be hyperactivation of MTL circuits, possibly representing inefficient compensatory activity. Later in the course of MCI, when considerable memory deficits are present, MTL regions are no longer able to activate during attempted learning, as is the case in AD dementia. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, such as for use in clinical trials.     

Cognitive profiling of Parkinson disease patients with mild cognitive impairment and dementia

BackgroundPrevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD) is variable because different classification criteria are applied and there is lack of consensus about neuropsychological tests and cut-off used for cognitive profiling. Given the important therapeutic consequences for patient management, we aimed at identifying suitable diagnostic cognitive tests and respective screening cut-off values for MCI and dementia in PD (PDD).MethodsWe evaluated 105 PD patients using an extensive neuropsychological battery categorized as PD without cognitive impairment (PD-CNT) (35%), PD-MCI (47%) and PDD (18%) based on established criteria and calculated Receiver Operating Characteristic (ROC) curves.ResultsWe found different sensitivity and specificity among neuropsychological tests in detecting PD-MCI and PDD. In particular performance in attention/set shifting, verbal memory and language abilities, discriminated both PD-MCI and PDD from PD-CNT. Abilities involved mainly in semantic retrieval mechanisms discriminated PD-CNT from PD-MCI but also PD-MCI from PDD. Finally deficits in executive and visual-spatial abilities were only affected in PDD.ConclusionOur data point to an independent and different load of each test in defining different PD cognitive statuses. These findings can help selection of appropriate cognitive batteries in longitudinal studies and definition of stage-specific therapeutic targets.     

遗忘型轻度认知损害患者的前瞻性记忆障碍

目的 探讨遗忘型轻度认知损害(amnesia mild cognitive impairment,aMCI)患者前瞻性记忆(prospective memory,PM)改变的特征,初步了解基于事件的PM(event-based prospective memory,EBPM)和基于时间的PM(time-based prospective memory,TBPM)在aMCI患者中的损害情况.方法 建立PM的神经心理学测验方法,对30例aMCI患者以及年龄、受教育程度相匹配的30名健康老年人进行测试.结果 与健康对照组[EBPM:(2.33±0.66)分、TBPM:(4.90±1.03)分]相比,aMCI组的EBPM成绩[(0.90±1.09)分]和TBPM成绩[(4.23 ±1.14)分]差异均有统计学意义(t=-6.143,P<0.01;t=-2.383,P<0.05).结论 aMCI患者的记忆障碍不仅表现为回顾性记忆(retrospective memory,RM)损害,PM损害可能更为突出,且EBPM的损害程度大于TBPM和RM,提示EBPM的测查可能有利于aMCI的早期识别.