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.     

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.     

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。     

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