Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance

The current study tested the accuracy of primary MRI and cerebrospinal fluid (CSF) biomarker candidates and neuropsychological tests for predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. In a cross-validation paradigm, predictor models were estimated in the training set of AD (N = 81) and elderly control subjects (N = 101). A combination of CSF t-tau/Aβ(1-4) ratio and MRI biomarkers or neuropsychological tests (free recall and trail making test B (TMT-B)) showed the best statistical fit in the AD vs. HC comparison, reaching a classification accuracy of up to 64% when applied to the prediction of MCI conversion (3.3-year observation interval, mean = 2.3 years). However, several single-predictor models showed a predictive accuracy of MCI conversion comparable to that of any multipredictor model. The best single predictors were right entorhinal cortex (prediction accuracy = 68.5% (95% CI (59.5, 77.4))) and TMT-B test (prediction accuracy 64.6% (95% CI (55.5, 73.4%))). In conclusion, short-term conversion to AD is predicted by single marker models to a comparable degree as by multimarker models in amnestic MCI subjects.     

Mild cognitive impairment as predictor for Alzheimer's disease in clinical practice: effect of age and diagnostic criteria

BACKGROUND: We investigated whether the predictive accuracy of mild cognitive impairment (MCI) for Alzheimer-type dementia (AD) in a clinical setting is dependent on age and the definition of MCI used. METHOD: Non-demented subjects older than 40 (n=320) who attended a memory clinic of a university hospital were reassessed 5 years later for the presence of AD. MCI was diagnosed according to the criteria of amnestic MCI, mild functional impairment (MFI), ageing-associated cognitive decline (AACD), and age-associated memory impairment (AAMI). The main outcome measure was the area under the curve (AUC) of a receiver operating characteristic (ROC) curve. Analyses were conducted on the entire sample and on subgroups of subjects aged 40-54, 55-69 and 70-85 years. RESULTS: A diagnosis of AD at follow-up was made in 58 subjects. Four of them were in the 40-54 age group, 29 in the 55-69 age group and 25 in the 70-85 age group. The diagnostic accuracy in the entire sample was low to moderately high with AUCs ranging from 0.56 (AACD) to 0.75 (amnestic MCI). A good predictive accuracy with an AUC >0.80 was only observed in subjects aged 70-85 using the criteria of amnestic MCI (AUC=0.84). CONCLUSIONS: The predictive accuracy of MCI for AD is dependent on age and the definition of MCI used. The predictive accuracy is good only for amnestic MCI in subjects 70-85 years. As subjects with prodromal AD are often younger than 70, the usefulness of MCI as predictor of AD in clinical practice is limited.     

Genuine memory deficits in dementia

Controlled learning with effective cued recall is needed to distinguish between genuine memory deficits due to impairment of specific memory processes and apparent memory deficits due to impairment of other cognitive processes, such as attention, that can limit memory. Effective cued recall is needed for accurate measurement of memory in the elderly because cued recall reveals learning not shown by free recall. When a search procedure was used to control processing for effective encoding and cued recall, nondemented elderly adults recalled all or nearly all 16 items on each trial. Decreased recall by demented patients even after they carried out the same effective processing showed genuine memory impairment that was not due to other cognitive deficits. Cued recall was better than either free recall or recognition in discriminating elderly persons with dementia from those without dementia and by itself accounted for 75 % of the variation in dementia status. Cued recall was especially useful for identifying patients with mild to moderate dementia who were not identified by free recall. It is proposed that elderly persons who have decreased cued recall of a 16‐item list after controlled learning have genuine memory impairment and therefore are likely to be demented because other causes of amnestic syndromes are relatively infrequent in the aged. Controlled learning with effective cued recall should be useful for screening of elderly persons for dementia.     

Olfactory identification deficits and MCI in a multi-ethnic elderly community sample

Odor identification deficits occur in Alzheimer's disease (AD) and mild cognitive impairment (MCI), and predict clinical conversion from MCI to AD. In an epidemiologic study conducted in a multi-ethnic community elderly sample (average 80 years old), the University of Pennsylvania Smell Identification Test (UPSIT, range 0-40) was administered to 1092 non-demented subjects. Women (mean 26.6, S.D. 6.6) scored higher than men (mean 24.4, S.D. 7.4, p<.02), and ethnic differences were not significant after controlling for age and education. UPSIT scores correlated inversely with age (r=-0.24, p<.0001) and positively with Selective Reminding Test immediate recall (r=0.33), delayed recall (r=0.28), category fluency (r=0.28) and the 15-item Boston Naming Test (r=0.23), all ps<.0001. In a sub-sample in which MRI was done, UPSIT scores showed a significant correlation with hippocampal volume (n=571, r=0.16, p<.001) but not entorhinal cortex volume nor total number of white matter hyperintensities. In ANOVA, UPSIT scores differed (p<.0001) as a function of MCI classification: no MCI (mean 26.6, S.D. 6.8), non-amnestic MCI (mean 24.4, S.D. 7.2), and amnestic MCI (mean 23.5, S.D. 6.7). The difference between amnestic MCI and no MCI remained significant after controlling for relevant covariates. These findings indicate that the predictive utility of olfactory identification deficits for decline from no MCI to MCI and AD needs to be assessed in longitudinal studies of elderly community samples.     

Differentiation between mild cognitive impairment, Alzheimer's disease and depression by means of cued recall

BACKGROUND: Discriminating Alzheimer's disease (AD) and mild cognitive impairment (MCI) from depression is a challenge in psychogeriatric medicine. A study was set up to ascertain whether cued recall could be useful in differentiating early AD and MCI from depression among elderly individuals. METHOD: The Visual Association Test (VAT) and the Memory Impairment Screen-plus (MIS-plus) were administered together with the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS) to 40 MCI patients, 35 mild AD patients, 46 depressed patients and 52 healthy control subjects. RESULTS: A one-way analysis of variance (ANOVA) followed by post-hoc Scheffé tests showed that AD patients had significantly lower cued recall scores (i.e. combined VAT and MIS-plus scores) than MCI patients, who in turn had lower scores than depressed patients. The scores of depressed patients and controls were not significantly different. Discriminant analysis revealed that 94% of the AD patients and 96% of the depressed patients could be classified correctly by means of the GDS and the cued recall sores. Receiver operating characteristic (ROC) curves identified an optimal cut-off score of 8 (maximum score 12) for differentiating AD and MCI patients from depressed elderly patients and controls. Applying this cut-off, a sensitivity of 83% (58%) and a specificity of 85% (85%) was obtained when differentiating AD (MCI) from depression. CONCLUSIONS: Cued recall, operationalized by the combined scores of VAT and MIS-plus, is a useful method for differentiating AD patients from depressed individuals and healthy controls. Probably because of the great heterogeneity among MCI patients, the diagnostic power of cued recall decreases when applied to differentiate MCI from depression.     

Sensitivity and specificity of neuropsychological tests for mild cognitive impairment,vascular cognitive impairment and Alzheimer's disease

BACKGROUND: Early diagnosis of dementia is important for those who might benefit from treatment. We designed a brief comprehensive neuropsychological test battery to help differentiate control subjects from patients with mild cognitive impairment (MCI) and dementia. METHOD: The battery included tests of memory, attention, executive function, speed, perception and visuospatial skills. It was administered to subjects from the OPTIMA cohort: 51 controls, 29 with MCI, 60 with 'possible' or 'probable' Alzheimer's disease (AD) (NINCDS/ADRDA) and 12 with cerebrovascular disease (CVD). Mann-Whitney U tests were used to compare performance of controls with other diagnostic groups. The sensitivity and specificity of the tests were determined using Receiver Operating Characteristic curve analyses. The effects of age, gender and years of education on test performance were determined with Spearman's rank correlations. RESULTS: The AD group performed worse than controls on all tests except an attention task. The Hopkins Verbal Learning Test and The Placing Test for episodic memory showed significant discriminative capacity between controls and other groups. Attention and processing speed tests discriminated CVD from controls. Category fluency, episodic memory tests and the CLOX test for executive function distinguished MCI from AD. Spearman's correlations showed negative associations between age and processing speed. Years of education affected performance on all tests, except The Placing Test. CONCLUSIONS: Certain neuropsychological tests have been shown to be sensitive and specific in the differential diagnosis of various types of dementia and may prove to be useful for detection of MCI.     

Oxidative stress and antioxidant defenses in mild cognitive impairment: A systematic review and meta-analysis

This study aims to systematically review and meta-analyze the nitro-oxidative stress (O&NS)/antioxidant (ANTIOX) ratio in the peripheral blood of people with mild cognitive impairment (MCI). We searched PubMed, Scopus, Google Scholar, and Web of Science for articles published from inception until July 31, 2021. Forty-six studies on 3.798 MCI individuals and 6.063 healthy controls were included. The O&NS/ANTIOX ratio was significantly higher in MCI than in controls with a Standardized Mean Difference (SMD)= 0.378 (95% CI: 0.250; 0.506). MCI individuals showed increased lipid peroxidation (SMD=0.774, 95%CI: 4.416; 1.132) and O&NS-associated toxicity (SMD=0.621, CI: 0.377; 0.865) and reduced glutathione (GSH) defenses (SMD=0.725, 95%CI: 0.269; 1.182) as compared with controls. MCI was also accompanied by significantly increased homocysteine (SMD=0.320, CI: 0.059; 0.581), but not protein oxidation, and lowered non-vitamin (SMD=0.347, CI: 0.168; 0.527) and vitamin (SMD=0.564, CI: 0.129; 0.999) antioxidant defenses. The results show that MCI is at least in part due to increased neuro-oxidative toxicity and suggest that treatments targeting lipid peroxidation and the GSH system may be used to treat or prevent MCI.     

Mild cognitive impairment: applicability of research criteria in a memory clinic and characterization of cognitive profile

BACKGROUND: We explored the applicability of recently proposed research criteria for mild cognitive impairment (MCI) in a memory clinic and changes in case definition related to which memory tests are used and the status of general cognitive function in MCI. METHOD: A total of 166 consecutive GP referrals to the Cambridge Memory Clinic underwent comprehensive neuropsychological and psychiatric evaluation. RESULTS: Of 166 cases, 42 were excluded (significant depression 8, established dementia 29 and other disorders 5). Of 124 non-demented, non-depressed patients, 72 fulfilled Petersen's criteria for amnestic MCI based upon verbal memory performance [the Rey Auditory Verbal Learning Test (RAVLT)] and 90 met criteria if performance on verbal and/or non-verbal memory tests [the Rey figure recall or the Paired Associates Learning test (PAL)] was considered. Of the 90 broadly defined MCI cases, only 25 had pure amnesia: other subtle semantic and/or attention deficits were typically present. A further 12 were classed as non-amnestic MCI and 22 as 'worried well'. CONCLUSIONS: Definition of MCI varies considerably dependent upon the tests used for case definition. The majority have other cognitive deficits despite normal performance on the Mini-mental State Examination (MMSE) and intact activities of daily living (ADL) and fit within multi-domain MCI. Pure amnesic MCI is rare.     

Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment

Different processes like microvascular dysfunction, free radical toxicity, beta-amyloid deposits, and Wallerian degeneration can cause functionally relevant disturbances of cerebral neuronal networks by myelin degeneration. Color-coded diffusion-tensor-imaging (ccDTI) allows the structural identification and quantification of myelinated fiber tracts. Particularly, posterior cingulate fiber tracts, which are regarded as important neuronal substrates of the network representing memory processing can be localized only imprecisely by conventional magnetic resonance imaging techniques. The posterior cingulate bundles were assessed by ccDTI in 17 patients with amnestic mild cognitive impairment (MCI), 25 patients with Alzheimer's dementia (DAT), and 21 age-matched controls. Additionally, DTI values were correlated with memory performance in the delayed verbal recall test. Fractional anisotropy and mean diffusivity differed significantly between MCI and controls, as well as between DAT and controls. Performance in the delayed verbal recall test of the entire study group correlated significantly with posterior cingulate bundle anisotropy and diffusivity. Using ccDTI seems, hence, a favorable strategy to detect and quantify the structural integrity of posterior cingulate white matter in MCI. Alterations of DTI parameters substantiate the involvement of white matter pathology in the development of MCI. Moreover, ccDTI could serve as in vivo method to investigate age and disease-related myelin alterations as potential morphological substrates of cognitive dysfunction.     

基于极限学习机的阿尔兹海默病辅助诊断

阿尔兹海默病是一种渐进发展式的痴呆疾病, 其脑部随着病情发展逐渐出现萎缩。利用磁共振脑图像解剖学特征的变化, 提出一种使用极限学习机来诊断阿尔兹海默病以及轻度认知障碍的方法。采用FreeSurfer软件, 分析从ADNI数据库的818份磁共振图像中得到的脑部解剖学特征。首先对这些特征使用线性回归模型来估计正常衰老引起的萎缩因素, 并将其从特征中去除;随后采用极限学习机作为分类器, 使用处理后的特征来诊断阿尔兹海默病和轻度认知障碍。在实验过程中, 通过十折交叉验证来测试该方法的诊断准确率、敏感度、特异度和曲线下面积。通过100次实验求平均的方式计算得出, 该方法诊断阿尔兹海默病的准确率达到87.62%, 曲线下面积达到94.25%;诊断轻度认知障碍的准确率达到73.38%, 敏感度达到83.88%, 其中年龄矫正能有效提高轻度认知障碍诊断的准确率。实验结果表明, 该方法能有效诊断阿尔兹海默病和轻度认知障碍。     

Subclassifications for mild cognitive impairment: prevalence and predictive validity

BACKGROUND: Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. Recently published results of the Current Concepts in MCI Conference suggested subclassifications for MCI (MCI-amnestic, MCI-multiple domains slightly impaired, MCI-single nonmemory domain) based on the recognized heterogeneity in the use of the term. These subclassifications have not been empirically validated to date. METHOD: A community sample of 1045 dementia-free individuals aged 75 years and over was examined by neuropsychological testing in a three-wave longitudinal study. The prevalences and the predictive validities for the subclassifications of MCI and their modifications (original criteria except for the report of subjective decline in cognitive function) were determined. RESULTS: The prevalence was 1 to 15% depending on the subset employed. Subjects with a diagnosis of MCI progressed to dementia at a rate of 10 to 55% over 2.6 years, depending on the subset employed. MCI-amnestic achieved the highest positive predictive power (PPP). ROC curves of the subclassifications for MCI indicate that all but one subset for MCI failed to predict dementia (MCI-multiple domains slightly impaired-modified: AUC=0.585, P<0.01, 95% CI, 0.517-0.653). The use of modified criteria for MCI (original criteria except for the report of subjective decline in cognitive function) is associated with a higher diagnostic sensitivity but also with a reduction in diagnostic specificity and PPP. CONCLUSIONS: Modified criteria should be applied if a concept for MCI with a high sensitivity is required and the original criteria (including subjective cognitive complaint) if a concept with high specificity and high PPP is required.     

APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive impairment to Alzheimer's disease

We have investigated whether the -86 C/T promoter polymorphism in CHRNA7 gene, the signal peptide polymorphism of the alpha1-antichymotripsin (ACT) gene or the APOE genotype are associated with an increased risk of mild cognitive impairment (MCI) or affect the risk of evolution to Alzheimer's disease (AD). We have followed up 89 patients with initial diagnoses of amnestic MCI for 49 months. Patients were separated into three groups: 27 subjects who remained with MCI, 40 that converted to AD before 20 months and 22 that converted to AD after. To assess the risk associated to each genotype a control group (n=90) without cognitive impairment was included. APOE4 allele was associated with an increased risk of MCI (OR: 6.04, 95% CI: 2.76-3.23; p<0.001) but did not have an effect on the probability of evolving AD. ACT or CHRNA7 genotypes were not associated with MCI but both appear to modify the risk of progression to dementia in opposing manners: ACT polymorphism increasing the risk to evolve to AD before 20 months (HR=2.03; 95% CI: 1-4.6; p=0.06) and CHRNA7 polymorphism protecting from evolution to dementia. Cox regression model demonstrated that ACT genotype confers a higher risk of rapid evolution to dementia than age or years of schooling. We conclude that APOE is a risk gene for amnestic MCI and that ACT and CHRNA7 may act in these patients as modifier genes for the time of progression to AD.     

芦山地震后5年雅安城市老人的认知功能及相关因素

目的:了解芦山地震5年后雅安城市老年人的认知功能现状及相关因素,为灾难性事件后老年人群心理健康及认知功能干预提供参考。方法:采取多阶段分层整群随机抽样方法,于2019年3月,选取雅安市区≥60岁老年人885名例,使用老年人一般信息调查表收集一般人口学信息、健康相关信息、受灾情况分布,采用MoCA量表(北京版)评估认知功能。结果:芦山地震后5年雅安城市老年人认知功能障碍患病率为14.9%,其中轻度为9.1%,中、重各为2.9%;不同受灾程度地区老年人的认知功能障碍患病率,差异无统计学意义。Logistics回归分析显示,年龄70~<80岁和≥80岁组的老年人更易出现认知功能障碍[OR=2.98(95%CI:1.72~5.15),OR=6.08(95%CI:3.51~10.55),均P<0.001],大专及以上受教育程度的老人不易出现认知功能障碍[OR=0.15(95%CI:0.05~0.44),P<0.001]。结论:高龄为芦山地震后5年雅安城市老人认知功能障碍的危险因素,受教育程度高为保护因素。     

Associations between sleep duration and cognitive impairment in mild cognitive impairment

The prevalence of mild cognitive impairment (MCI) increases among elderly people and is associated with a high risk of dementia. Identifying factors that may contribute to the progress of MCI to dementia is critical. The objective of this study was to examine the association of objective sleep with cognitive performance in MCI patients. A subsample of 271 participants with a diagnosis of probable Alzheimer's disease (AD; N = 50) or mild cognitive impairment (MCI; N = 121) and 100 persons who were not cognitively impaired (NI) were recruited from a large population‐based cohort in the island of Crete, Greece (3140 older adults aged >60 years). All participants underwent extensive neuropsychiatric/neuropsychological evaluation and a 3‐day 24‐hr actigraphy. Objective sleep variables and their association with neuropsychological performance were examined across the three groups, controlling for demographics, body mass index, depression, sleep apnea symptoms and psychotropic medications. Patients with AD had significantly longer 24‐hr total sleep time (TST) compared to the MCI and NI groups. Long 24‐hr TST was associated with reduced performance on tasks that placed significant demands on attention and processing speed in the MCI group and the AD group. Elderly patients with MCI have similar objective sleep duration to normal controls, whereas AD patients sleep longer. Long sleep duration in patients with multidomain subtypes of MCI is associated with critical non‐memory cognitive domains. It appears that within the MCI group those that sleep longer have more severe cognitive impairment.     

连线测验(中文修订版)在早期识别阿尔茨海默病中的作用

目的：中文修订版的连线测验（TMT）在识别轻度认知功能障碍（MCI）和轻度阿尔茨海默病（AD）中的作用。方法：对正常老人94名．遗忘型MCI组107例和轻度AD组54例进行MMSE、TMT在内的8种神经心理测验。结果：正常老人与MCI组TMT完成率均高于轻度AD组。年龄与教育程度对TMT—B的影响比TMT—A更大。TMT-A、B与MMSE、CFT模仿、CWCR、CFT回忆、AVLT延迟回忆均有显著相关性。完成TMT—A、B测验．NC组、MCI组与轻度AD组两两比较均有显著差异，TMT可以清楚的区分三组。结论：TMT对MCI病人有一定的辅助识别作用，对轻度AD病人有较强的辅助识别作用．     

C反应蛋白诊断新生儿败血症准确性的Meta分析

目的 探讨CRP诊断新生儿败血症的诊断价值.方法 计算机检索维普中文科技期刊数据库、中国期刊全文数据库、万方数据库、中国生物医学文献数据库、Medline、EMBASE、Cochrane图书馆、PubMed等数据库（检索时间为1989年1月至2011年7月）,获得CRP诊断新生儿确诊败血症的文献.采用QUADAS工具对纳入文献进行质量评价.采用MetaDisc 1.4和RevMan 5.0软件检验各文献间的异质性,并根据异质性结果选择相应的效应模型进行加权定量合并,计算敏感度和特异度及其95%CI.绘制受试者工作特征（SROC）曲线并计算曲线下面积（AUC）,并行敏感度分析.结果 20篇文献进入Meta分析.分析结果显示：CRP诊断新生儿败血症的汇总敏感度和特异度分别为0.69（95%CI：0.65～0.72）和0.87（95%CI：0.86～0.89）,SROC AUC为0.88,Q＊指数为0.81.CRP＞8 mg·L-1诊断新生儿败血症的汇总敏感度和特异度分别为0.88（95%CI：0.82～0.92）和0.86 （95%CI：0.81～0.90）,SROC AUC为0.94,Q＊指数为0.88;CRP≥8 mg·L-1诊断新生儿败血症的汇总敏感度和特异度分别为0.54（95%CI：0.47～0.61）和0.81（95%CI：0.76～0.85）,SROC AUC为0.80,Q＊指数为0.74;两者合并诊断新生儿败血症的汇总敏感度和特异度分别为0.70（95%CI：0.65～0.74）和0.83（95%CI：0.80～0.86）,SROC AUC为0.88,Q＊指数为0.82.在纳入文献中标本来源和检测方法的差异等非阈值效应因素是产生异质性的原因.结论 CRP对新生儿败血症诊断的敏感度和特异度较高,有助于早期诊断新生儿败血症.     

Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease

Mild cognitive impairment (MCI) defines a group of otherwise healthy elderly subjects with a markedly elevated risk of developing Alzheimer's disease (AD). In the search for biomarkers of MCI, we assessed whether MCI shares neurochemical abnormalities with AD in areas affected early in the course of the disease. As a secondary study aim, we tested to what extent neurochemical findings reflect neuropsychological deficits. Proton spectroscopy was performed in 19 MCI patients, 18 AD patients and 22 age and gender matched controls (CON) within the parietal gray and white matter (PWM and PGM) and the hippocampus (HIP). The cognitive test battery used included measures compiled by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The N-acetyl-aspartate to creatine ratio (NAA/Cr) was significantly reduced in the HIP of MCI and AD compared with CON (p < 0.05). Only AD patients showed parietal abnormalities, namely significantly elevated myoinositol (mI/Cr and mI/NAA) in PGM, reduced NAA/Cr and elevated mI/NAA in PWM. MCI subjects were significantly impaired in categorical verbal fluency (VF) (p < 0.001) and delayed verbal recall (DVR) (p < 0.001). VF was positively correlated with hippocampal NAA/Cr (p < 0.05) and parietal mI/NAA (p < 0.05). In summary, this study demonstrates shared neurobiological hippocampal abnormalities in MCI and AD, whereas parietal lobe neurochemical profiles and functions were normal in MCI. Thus, biological evidence is provided that MCI represents a precursor stage of AD. Moreover, multivoxel 1H MRS may enable an objective staging of the neurodegenerative process underlying the age-dependent cognitive deficits eventually leading to dementia.     

Conversion of MCI to dementia: Role of proton magnetic resonance spectroscopy

Mild cognitive impairment (MCI) represents a heterogeneous group of cognitive disturbances at high risk of dementia. The amnestic subtype (aMCI) might be a prodromal state of Alzheimer's disease (AD). The aim of this study is the identification, by proton magnetic resonance spectroscopy (1H MRS), of modifications in brain metabolites able to detect subjects with aMCI at risk of conversion towards AD. Twenty-five subjects with aMCI and 29 normal elderly were enrolled; they underwent a comprehensive clinical and instrumental assessment, a cerebral 1H MRS scan to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and creatine (Cr) in the paratrigonal white matter, bilaterally. After 1 year, 5 MCI subjects became demented (progressive MCI, pMCI). Their baseline levels of metabolites were compared with those evaluated in stable MCI (sMCI) and in controls. We observed a significant difference of the NAA/Cr ratio between pMCI (1.48+/-0.08) and sMCI (1.65+/-0.12) and between pMCI and controls (1.63+/-0.16) in the left hemisphere, suggesting that this metabolic alteration can be detected before the clinical appearance of dementia.     

Are the CSF levels of 24S-hydroxycholesterol a sensitive biomarker for mild cognitive impairment?

There is a need for effective biomarkers showing whether or not a patient with mild cognitive impairment (MCI) will progress to Alzheimer's disease (AD) with dementia. At the present three cerebrospinal fluid (CSF) biomarkers are in general use: total tau, phospho-tau and beta-Amyloid. These markers are regarded to have high capacity to differentiate early AD from normal ageing. We have analysed CSF levels of a new marker for neuronal degeneration, 24S-hydroxycholesterol (24OHC) in patients with MCI. For reasons of comparison, we also analysed these levels in patients with AD. There was a significant correlation between CSF levels of 24OHC and total tau (as well as phospho-tau) in both groups of patients. Fifty percent of the patients contemplated for MCI were found to have elevated levels of 24OHC (using a 95th upper percentile set cut-off). All the MCI patients with normal levels of 24OHC had normal levels of the other markers. In patients with AD, the percentages of those with increased levels of 24OHC, tau and phospho tau were similar (55-67%). In this pilot study, we discuss the possibility that 24OHC may be a sensitive test for MCI.     

Metabolic syndrome, mild cognitive impairment, and progression to dementia. The Italian Longitudinal Study on Aging

We investigated the relationship of metabolic syndrome (MetS) and its individual components with incidence of mild cognitive impairment (MCI) and its progression to dementia in a large longitudinal Italian population-based sample with a 3.5-year follow-up. A total of 2097 participants from a sample of 5632 65-84-year-old subjects from the Italian Longitudinal Study on Aging were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. MCI, dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were classified using current published criteria. Among MCI patients those with MetS (N = 49) had a higher risk of progression to dementia (HR, 4.40; 95% CI, 1.30-14.82) compared with those without MetS (N = 72). After a multivariate adjustment, the risk in MCI patients with MetS approximately doubled (multivariate adjusted HR, 7.80, 95% CI 1.29-47.20) compared with those MCI without MetS. Finally, among non-cognitively impaired individuals there were no significant differences in risks of developing MCI in those who were affected by MetS (N = 608) in comparison with those without MetS (N = 837), as well as excluding those individuals with undernutrition or low inflammatory status with or without undernutrition. In our population, among MCI patients the presence of MetS independently predicted an increased risk of progression to dementia over 3.5 years of follow-up.