遗忘型轻度认知损害的脑机制研究
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摘要
老年人认知功能存在一个动态变化的过程,从认知正常者到增龄相关记忆损害(A AMI),再到轻度认知损害(MCI)及至痴呆。对于痴呆尚缺乏有效的治疗措施,及早发现高风险者以及出现最早期症状的患者,将有助于找到合适的对象降低风险和研究预防措施。记忆型MCI (aMCI)被认为阿尔茨海默型痴呆(AD)的高危人群,但国内筛查aMCI的量表存在信效度不明确或者划界分不清的缺点；脑功能影像学研究已发现,颞顶区脑功能下降可以预测MCI是否进展为AD；但其它部位是否有预测意义,仍有待进一步证实。本研究从2个方面进行：(1)确定简易智能量表(MMSE)在社区老年人中筛查MCI的划界分(以年龄、文化程度进行划界),以此作为aMCI的入组标准之一；(2)对aMCI进行单光子发射计算机断层摄影(SPECT)、~(18)氟-氟脱氧葡萄糖-兼容型PET (18F-FDG-hPET)检查,并与AD(轻度、中-重度)、健康对照组(HC)进行对照,研究aMCI的脑功能机制。结果表明：(1)小学及以下文化组,MMSE筛查MCI的最优分界值为≤27分；中学及以上文化组,MMSE筛查MCI的最优分界值为≤28分。不论分组年龄,MMSE筛查MCI的最优分界值为≤28分。(2)脑18F-FDG-hPET与99mTc-ECD-SPECT显像检查发现,与HC比较,aMCI颞叶、顶叶、海马葡萄糖代谢率减低；血流减低主要表现在颞叶、顶叶及海马部位。而AD大脑皮层放射性整体分布不均匀,轻度患者出现额叶、颞叶、顶叶、海马等脑叶葡萄糖代谢率及血流减低,随着疾病进展发展至中重度期,出现额叶、颞叶、顶叶、枕叶全脑区域葡萄糖代谢率及血流减低。进一步分析aMCI脑代谢、脑血流改变与年龄、教育、神经心理学测量的相关性显示：(1)脑代谢改变：海马左右两侧与年龄负相关；右顶叶与ADL负相关；左楔前叶、右丘脑和尾状核与WMS正相关；左前扣带回、左楔前叶、左尾状核、左侧海马与MMSE正相关。(2)脑血流改变：右侧楔前叶、前扣带回、丘脑、壳核与教育负相关；右颞叶与ADL负相关；左顶叶、右枕叶与ADL正相关；左后扣带回与WMS正相关；左尾状核与MMSE正相关。该结果证实健康老年人、aMCI与AD是一个连续的认知发展过程；颞叶、顶叶的功能下降提示aMCI发展为AD的可能性高；顶叶、枕叶脑功能受损可能是极早期AD的表现。
It has been commonly accepted that cognitive function impairment in the old is a dynamic progression, which can be separated into four steps:normal, age associated memory impairment (AAMI), mild cognitive impairment (MCI) and dementia. Unfortunately, few promising and effective treatment or intervention of dementia are, as of yet, available. Therefore, in order to reduce the risk of dementia and to develop better diagnostic tool, it is important to identify people who are high susceptibility or have been in the first stage. It has been thought that people diagnosed as amnestic MCI (aMCI) are much more susceptible to suffer Alzheimer's disease (AD). However, assessments about aMCI are not reliable, and cutoff score in such assessments is confusing in China. Some neuroimaging studies have showed that people with dysfunction in temporal and parietal lobe have high risk to develop to AD from aMCI. Further researches are needed to estimate whether other regions are associated to this deterioration. In the present study, there are two main parts. Firstly, we are interested in the cutoff score of MMSE (Mini-Mental State Examination) in the community of the old, when age and education were taken into account. The cutoff score could be considered as a prerequisite of assessment of aMCI. Secondly, we aimed to investigate the corresponding underlying mechanism of aMCI by using SPECT and 18F-fluorodeoxyglucose- hybrid PET. We made comparison among patients with aMCI, AD patient (mild, moderate, and severe group), and health control (HC). As the result, firstly, we found that MMSE had a cutoff score 27 when participants' education was primary school or below. Then, cutoff score of MMSE was 28 when participants' education level was junior school or above. In addition, regardless of age, the cutoff score of MMSE was 28. Secondly, in terms of the findings by 18F-FDG-hPET and 99mTc-ECD-SPECT, we revealed hypometabolism in temporal lobe, parietal lobe and hippocampus in patients with aMCI, compared with health check (HC). Morever, reduced normalised radioactivity was detected in the cortex of AD patients. Specifically, hypometabolism and hypoperfusion were found in the frontal lobe, temporal lobe, parietal lobe and hippocampus in the patients with mild AD. By the development into modetare/severe stage of AD, hypometabolism and hypoperfusion were revealed in frontal lobe, tempral lobe, parietal lobe and occipital lobe. By taking cerebral metabolism, blood flow, age, education and neuropsychology assessment into account, we could draw two main conclusions. Firstly, cerebral metabolism are negetively correlated with age in both left and right sides of hippocampus, negatively correlated with ADL in right parietal lobe, positively correlated with WMS in left precuneus, thalamus and caudate nucleus, positively correlated with MMSR in left anterior angulate cortex, left precuneus, left caudate nucleus and left hippocampus. Secondly, cerebral blood flow were negatively related with education in right precuneus, anterior angulate cortex, thalamus and putamen, negatively related with ADL in right temporal lobe, positively related with ADL in left parietal lobe and right occipital lobe, positively related with WMS in left posterior cingulate cortex, positively related with MMSE in left caudate nucleus. In sum, the present study verified that cognitive function change can be seen as a progression from normal, aMCI to AD in the old. aMCI Patients with dysfunction in temporal and parietal lobe are highly susceptible to develop as AD, and dysfunction in parietal and occipital lobe can be seen as the earliest diagnostic symptom.
It has been commonly accepted that cognitive function impairment in the old is a dynamic progression, which can be separated into four steps:normal, age associated memory impairment (AAMI), mild cognitive impairment (MCI) and dementia. Unfortunately, few promising and effective treatment or intervention of dementia are, as of yet, available. Therefore, in order to reduce the risk of dementia and to develop better diagnostic tool, it is important to identify people who are high susceptibility or have been in the first stage. It has been thought that people diagnosed as amnestic MCI (aMCI) are much more susceptible to suffer Alzheimer's disease (AD). However, assessments about aMCI are not reliable, and cutoff score in such assessments is confusing in China. Some neuroimaging studies have showed that people with dysfunction in temporal and parietal lobe have high risk to develop to AD from aMCI. Further researches are needed to estimate whether other regions are associated to this deterioration. In the present study, there are two main parts. Firstly, we are interested in the cutoff score of MMSE (Mini-Mental State Examination) in the community of the old, when age and education were taken into account. The cutoff score could be considered as a prerequisite of assessment of aMCI. Secondly, we aimed to investigate the corresponding underlying mechanism of aMCI by using SPECT and 18F-fluorodeoxyglucose- hybrid PET. We made comparison among patients with aMCI, AD patient (mild, moderate, and severe group), and health control (HC). As the result, firstly, we found that MMSE had a cutoff score 27 when participants' education was primary school or below. Then, cutoff score of MMSE was 28 when participants' education level was junior school or above. In addition, regardless of age, the cutoff score of MMSE was 28. Secondly, in terms of the findings by 18F-FDG-hPET and 99mTc-ECD-SPECT, we revealed hypometabolism in temporal lobe, parietal lobe and hippocampus in patients with aMCI, compared with health check (HC). Morever, reduced normalised radioactivity was detected in the cortex of AD patients. Specifically, hypometabolism and hypoperfusion were found in the frontal lobe, temporal lobe, parietal lobe and hippocampus in the patients with mild AD. By the development into modetare/severe stage of AD, hypometabolism and hypoperfusion were revealed in frontal lobe, tempral lobe, parietal lobe and occipital lobe. By taking cerebral metabolism, blood flow, age, education and neuropsychology assessment into account, we could draw two main conclusions. Firstly, cerebral metabolism are negetively correlated with age in both left and right sides of hippocampus, negatively correlated with ADL in right parietal lobe, positively correlated with WMS in left precuneus, thalamus and caudate nucleus, positively correlated with MMSR in left anterior angulate cortex, left precuneus, left caudate nucleus and left hippocampus. Secondly, cerebral blood flow were negatively related with education in right precuneus, anterior angulate cortex, thalamus and putamen, negatively related with ADL in right temporal lobe, positively related with ADL in left parietal lobe and right occipital lobe, positively related with WMS in left posterior cingulate cortex, positively related with MMSE in left caudate nucleus. In sum, the present study verified that cognitive function change can be seen as a progression from normal, aMCI to AD in the old. aMCI Patients with dysfunction in temporal and parietal lobe are highly susceptible to develop as AD, and dysfunction in parietal and occipital lobe can be seen as the earliest diagnostic symptom.
引文
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