Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease

Magnesium deficiency is present in several chronic, age-related diseases, including cardiovascular, metabolic and neurodegenerative diseases. Alzheimer's disease (AD) is the most common cause of dementia. The aim of the present study was to study magnesium homeostasis in patients with mild to moderate AD. One hundred and one elderly (≥65 years) patients were consecutively recruited (mean age: 73.4±0.8 years; M/F: 42/59). In all patients, a comprehensive geriatric assessment was performed including cognitive and functional status. Admission criteria for the AD group (diagnosed according to the DSM-IV and the NINCDS-ADRDA criteria) included: mild to moderate cognitive impairment (MMSE score: 11-24/30, corrected for age and education). Blood samples were analyzed for serum total magnesium (Mg-tot) and serum ionized magnesium (Mg-ion). AD patients had significantly lower MMSE scores (20.5±0.7 vs 27.9±0.2; p<0.001), and for the physical function tests. Mg-ion was significantly lower in the AD group as compared to age-matched control adults without AD (0.50±0.01 mmol/L vs 0.53±0.01 mmol/L; p<0.01). No significant differences were found in Mg-tot between the two groups (1.91±0.03 mEq/L vs 1.95±0.03 mEq/L; p=NS). For all subjects, Mg-ion levels were significantly and directly related only to cognitive function (Mg-ion/MMSE r=0.24 p<0.05), while no significant correlations were found in this group of patients between magnesium and ADL or IADL. Our results show the presence of subclinical alterations in Mg-ion in patients with mild to moderate AD.     

不同认知功能障碍程度阿尔茨海默病患者海马、内嗅皮层体积变化及其与MMSE评分的关系

目的 探讨不同认知功能障碍程度的患者阿尔兹海默病（AD）海马、内嗅皮层体积的变化,及其与简易精神状态检查表（MMSE）评分的相关性。方法 横断面研究。纳入2017年9月—2021年9月联保部队第九六〇医院淄博院区86例AD患者临床和影像学资料,其中男54例、女32例,年龄55~87（73.9±8.1）岁。根据临床痴呆评定量表（CDR）评分将86例患者分为3组,其中36例CDR评分0.5分患者为轻度认知障碍（MCI）组,21例1分患者为轻度AD组,29例2~3分患者为中重度AD组。患者均应用MRI测量双侧海马体积、内嗅皮层体积,采用MMSE评分评估患者认知功能。观察指标：（1）比较3组患者性别、年龄、受教育年限等临床基线资料,以及MMSE评分;（2）比较3组患者海马体积和内嗅皮层体积;（3）分析AD患者MMSE评分与海马、内嗅皮层体积的相关性。结果 （1）3组患者性别、年龄、受教育年限等临床基线资料比较差异均无统计学意义（P值均>0.05）。MCI组、轻度AD组、中重度AD组患者MMSE评分依次降低,差异有统计学意义（F=113.29,P<0.001）。（2）MCI组、轻度AD组、中重度AD组左右侧海马体积MRI测量值分别为（3.24±0.32）cm³和（3.22±0.31）cm³、（2.72±0.53）cm³和（2.84±0.56）cm³、（2.31±0.55）cm³和（2.46±0.54）cm³,左右侧内嗅皮层体积分别为（1.42±0.26）cm³和（1.39±0.27）cm³、（1.28±0.24）cm³和（1.24±0.25）cm³、（1.04±0.31）cm³和（1.06±0.34）cm³。3组患者左右侧海马体积、内嗅皮层体积MRI测量值比较,均为MCI组>轻度AD组>中重度AD组,差异均有统计学意义（P值均<0.05）。（3）86例AD患者MMSE评分10~27（20.9±5.2）分,与左右两侧海马体积、内嗅皮层体积MRI测量值均呈正相关（r=0.82、0.81、0.73、0.72,P值均<0.001）。结论 随着认知功能障碍程度的加重,AD患者海马、内嗅皮层体积MRI测量值逐渐减小,且MMSE评分与海马、内嗅皮层体积存在相关性。     

Vascular predictors of cognitive decline in patients with mild cognitive impairment

Our aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). After a 12-month follow-up period, neuropsychological examinations demonstrated a progression to dementia in 21 patients. Pathological values of BHI and IMT significantly increased the risk of conversion (BHI: odds ratio, 5.80; 95% confidence interval, 1.83-18.37, p < 0.05; IMT: odds ratio, 3.08; 95% confidence interval, 1.02-9.33; p < 0.05, multinomial logistic regression analysis). Comparison between patients with all normal values and those with the simultaneous alteration of the 2 vascular indexes showed an increase in the risk of conversion from 9% to 33% (ordinal regression analysis). Our findings show that alterations of cerebral vessel functional and anatomic status increase the risk of conversion from MCI to dementia.     

Hippocampal volume is an independent predictor of cognitive performance in CADASIL

Recent evidence suggests that hippocampal changes are present in vascular cognitive impairment but their importance and relationship with ischaemic mechanisms remain controversial. To investigate these issues we performed MRI and cognitive assessment in a large cohort (n=144) of patients with CADASIL, a hereditary small vessel disease and model of pure vascular cognitive impairment. Dementia status was ascribed according to DSM-IV and global cognitive function assessed with the Minimental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Hippocampal volume (HV) correlated with age (r=-0.33, p<0.001), brain volume (r=0.39, p<0.001) and lacunar lesion volume (r=-0.23, p=0.008), but not white matter lesions or microhaemorrhages. HV was reduced in dementia (2272+/-333 mm(3) versus 2642+/-349 mm(3), p<0.001) in the whole cohort and the subgroup progressing to dementia before age 60. HV correlated with MMSE (r=0.30, p<0.001), MDRS (r=0.40, p<0.001) and in a multivariate model predicted cognition independent of typical vascular lesions and whole brain atrophy. These findings strengthen the view that hippocampal atrophy is an important pathway of cognitive impairment in vascular as well as degenerative disease.     

Decreases in soluble alpha-synuclein in frontal cortex correlate with cognitive decline in the elderly

Alpha-synuclein (ASN) is a presynaptic protein and major component of Lewy bodies. It is considered important in the pathogenesis of Alzheimer's disease (AD), but its relevance to progressive cognitive decline in aging is largely unknown. To address this issue, ASN immunoreactivity was measured in frontal cortex of elderly individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI) and early AD using a Western blot technique and a polyclonal antibody to ASN. ASN immunoreactivity was significantly lower in AD than in MCI and NCI, but there was no difference between MCI and NCI. The ASN immunoreactivity correlated with CERAD diagnosis, as well as Mini-Mental State Exam (MMSE) score, global neuropsychologic z-score and some, but not all, frontal neuropsychology measures. Clinical correlations were stronger for ASN than synaptophysin immunoreactivity assessed in a similar manner. The correlation with MMSE was robust when NCI cases were considered separately, suggesting that decreases in soluble ASN may be an early feature of cognitive decline in aging and AD.     

Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers

In this longitudinal study we investigated change over time in cerebrospinal fluid (CSF) levels of amyloid-beta 40 and 42 (Aβ40 and Aβ42), total tau (tau), tau phosphorylated at threonine 181 (ptau-181), isoprostane, neurofilaments heavy (NfH) and light (NfL). Twenty-four nondemented subjects, 62 mild cognitive impairment (MCI) and 68 Alzheimer's disease (AD) patients underwent 2 lumbar punctures, with minimum interval of 6, and a mean ± SD of 24 ± 13 months. Linear mixed models were used to assess change over time. Amyloid-beta 42, tau, and tau phosphorylated at threonine 181, differentiated between diagnosis groups (p < 0.05), whereas isoprostane, neurofilaments heavy, and NfL did not. In contrast, effects of follow-up time were only found for nonspecific CSF biomarkers: levels of NfL decreased, and levels of isoprostane, amyloid-beta 40, and tau increased over time (p < 0.05). Isoprostane showed the largest increase. In addition, increase in isoprostane was associated with progression of mild cognitive impairment to AD, and with cognitive decline as reflected by change in Mini Mental State Examination (MMSE). Contrary to AD-specific markers, nonspecific CSF biomarkers, most notably isoprostane, showed change over time. These markers could potentially be used to monitor disease progression in AD.     

Progression of tau pathology in cholinergic Basal forebrain neurons in mild cognitive impairment and Alzheimer's disease

Tau is a microtubule-associated protein that forms neurofibrillary tangles (NFTs) in the selective vulnerable long projection neurons of the cholinergic basal forebrain (CBF) in Alzheimer's disease (AD). Although CBF neurodegeneration correlates with cognitive decline during AD progression, little is known about the temporal changes of tau accumulation in this region. We investigated tau posttranslational modifications during NFT evolution within the CBF neurons of the nucleus basalis (NB) using tissue from subjects with no cognitive impairment, mild cognitive impairment, and AD. The pS422 antibody was used as an early tau pathology marker that labels tau phosphorylated at Ser422; the TauC3 antibody was used to detect later stage tau pathology. Stereologic evaluation of NB tissue immunostained for pS422 and TauC3 revealed an increase in neurons expressing these tau epitopes during disease progression. We also investigated the occurrence of pretangle tau events within cholinergic NB neurons by dual staining for the cholinergic cell marker, p75(NTR), which displays a phenotypic down-regulation within CBF perikarya in AD. As pS422+ neurons increased in number, p75(NTR)+ neurons decreased, and these changes correlated with both AD neuropathology and cognitive decline. Also, NFTs developed slower in the CBF compared with previously examined cortical regions. Taken together, these results suggest that changes in cognition are associated with pretangle events within NB cholinergic neurons before frank NFT deposition.     

Intima-media thickness in treated and untreated patients with and without familial hypercholesterolemia: A systematic review and meta-analysis

Familial hypercholesterolemia (FH) is a common genetic disorder of lipoprotein metabolism leading to premature atherosclerosis. From early onset, status and progression of atherosclerosis of the large peripheral arterial walls can be quantified by ultrasound intima-media thickness (IMT) measurements. Here we describe differences in IMT in treated and untreated FH patients versus unaffected controls over a broad age range. We conducted a systematic literature search using MEDLINE, EMBASE and Trials.gov up to April 2020 for studies addressing IMT in FH patients and controls. Our search yielded 558 articles of which 42 (6,143 participants) were included. Meta-analysis showed a mean (95%CI) difference between FH patients vs controls of 0.11 (95%CI 0.06-0.15) mm in carotid IMT (p<0.001), and 0.47 (0.19-0.74) mm in femoral IMT (p <0.001). We found a smaller mean (95%CI) difference in carotid IMT in treated FH patients vs controls: 0.05 (0.03-0.08) mm (p <0.001), than in untreated FH patients vs controls 0.12 (0.03-0.21) mm (p=0.009). When plotted against age, the mean (95%CI) difference in carotid IMT between FH patients vs controls increases with 0.0018 (-0.0007-0.0042) mm/year. This increase was smaller in treated vs untreated FH patients, when compared to controls (0.0023 (0.0021 to 0.0025) mm/year vs 0.0104 (0.0100-0.0108) mm/year, respectively). Our findings suggest that more robust earlier treatment initiation and achieving treatment targets could be beneficial to reduce cardiovascular risk in patients with FH.     

老年痴呆患者认知功能障碍的分析

目的：采用MMSE评价AD患者认知功能障的特点。方法：采用MMSE量表对62例AD患者及159例正常老年人进行测评。应用t检验，多元回归分析对MMSE总分，各项得及其影响因素进行分析。结果：痴呆组MMSE总分及各项得分队体命外均显著低于正常对照组（P＜0．05）。轻度痴呆组在时间地点定向，语言即刻记忆，注意和计算，短程记忆、阅读理解，言语表达及图形描述得分析上高于中度痴呆组，差异有统计学显著性（P＜0．05）。受教育程度与MMSE总分，注意和计算，阅读理解及图形描述得分关系密切（P＜0．05），结论：老年性痴呆患者存在普遍的认知损害。受教育程度是影响痴呆患者智能的重要因素。     

A useful predictor of early atherosclerosis in obese children: serum high-sensitivity C-reactive protein

Childhood obesity seems to contribute to the development of vascular inflammation and the progression of arterial wall changes. High-sensitivity C-reactive protein (hs-CRP) has recently emerged as a useful biomarker for vascular inflammation associated with atherosclerosis. The objectives of this study were to evaluate the association of the serum hs-CRP level with ultrasonic findings of early atherosclerosis, carotid intima-media wall thickness (IMT) and brachial flow-mediated dilation (FMD), in obese children. Thirty eight obese children and 45 sex/age-matched healthy control children were recruited. Serum CRP levels were measured by the high-sensitive latex turbidimetric immunoassay, and we measured carotid IMT and brachial FMD using high-resolution B-mode ultrasonography. Obese children had significantly higher hs-CRP levels (1.40+/-0.74 mg/L vs. 0.55+/-0.49 mg/L, p<0.01), as well as increased IMT (0.52+/-0.09 mm vs. 0.41+/-0.07 mm, p<0.01) and impaired FMD (7.35+/-7.78% vs. 20.34+/-16.81%, p<0.01) compared to healthy controls. Serum hs-CRP correlated positively with IMT (r=0.413, p<0.05) and inversely with FMD (r=-0.350, p<0.05) in the obesity group. Measurement of the serum hs-CRP level is a simple, cheap, and highly reproducible assay and correlates with IMT and FMD in obese children. Thus, it would be a useful marker for evaluating and estimating the degree of atherosclerosis in children.     

The prognostic utility of CSF neurogranin in predicting future cognitive decline in the Alzheimer’s disease continuum: A systematic review and meta-analysis with narrative synthesis

Core cerebrospinal fluid (CSF) biomarkers (Aβ42, T-tau, P-tau) were included as supporting diagnostic criteria for Alzheimer’s Disease (AD), but they lack the power to predict AD progression. On the other hand, a new biomarker CSF Neurogranin (Ng) has been shown to predict cognitive decline. This systematic review aims to synthesise the prognostic utility of CSF Ng in predicting cognitive decline in the AD continuum. Seven databases were searched systematically from inception to 30 September 2020. Participants were 55 years or older, who had baseline and at least one follow-up cognitive assessments. Risk of bias was assessed using the Quality in Prognosis Studies tool. Meta-analysis was conducted by pooling standardised beta coefficients and adjusted hazard ratios. Thirteen studies were included and high-quality evidence suggests that CSF Ng predicts Mini-Mental State Examination (MMSE) decline in Aβ⁺ mild cognitive impairment (MCI). Moderate quality evidence showed that CSF Ng could predict the decline of memory and executive function in MCI. Narrative synthesis found that CSF Ng/Aβ42 was also likely to predict cognitive decline. More studies are required to validate the use of CSF Ng as an AD prognostic marker and its application in future development of drug treatment and diagnosis.     

The importance of intima-media thickness (IMT) measurements in monitoring of atherosclerosis progress after myocardial infarction

PurposeIntima-media thickness (IMT) assessed in peripheral arteries correlates with presence and progression of atherosclerosis in coronary arteries. IMT measurements may help to select high risk patients and evaluate the efficacy of the therapy used.AIMThe aim of the study was to assess the usefulness of ultrasonographic measurement of IMT in atherosclerosis progress monitoring in patients after myocardial infarction (MI).Patients and Methods70 men (mean age 52.8 ± 8.4) treated with PCI due to acute myocardial infarction, were enrolled in the study. All subjects underwent ultrasound examination of the IMT complex of: common carotid artery (CCA), carotid bulb and common femoral artery (CFA) during hospitalization and follow-up period (3.83 ± 1.29 years).ResultsDuring the follow-up 3 patients (4.3%) were not on any medications, 8 pts (11.4%) were on reduced doses of β-blocker, statin or ACE-I (non-compliant pts.). The others (compliant) – 59 pts (84.3%) received standard pharmacological treatment after MI. Nevertheless, an increase of IMT complex value after follow-up compared to initial IMT values of all examined peripheral arteries was observed (respectively: IMT CCA – 0.91±0.26 vs 1.10±0.36, p=0.002, IMT of carotid bulb – 1.31±0.55 vs 1.82±0.69, p=0.012, IMT CFA – 1.38±0.64 vs 1.97±0.75, p=0.014). Non-compliant patients had statistically significant higher IMT values after follow-up when compared to compliant subjects (1.62 vs 1.20, p= 0.017). Patients with higher IMT values were reported to have cardiac events more frequently during the follow-up (p<0.05).ConclusionsOur results provide evidence that ultrasonographic IMT complex assessment of peripheral arteries in everyday clinical practice allows monitoring efficacy of pharmacological therapy in CAD patients after MI. They also suggest treatment intensification if necessary.     

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.     

Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients

The Seoul Neuropsychological Screening Battery (SNSB) is one of the standardized neuropsychological test batteries widely used in Korea. However, it may be a bit too lengthy for patients with decreased attention span; and it does not provide the score of global cognitive function (GCF), which is useful for monitoring patients longitudinally. We sought to validate a dementia version of SNSB (SNSB-D) that was shorter than the original SNSB and contained only scorable tests with a GCF score of 300. We administered SNSB-D to patients with mild cognitive impairment (MCI) (n=43) and Alzheimer''s disease (AD) (n=93), and normal controls (NC) (n=77). MCI and AD groups had GCF scores significantly different from NC group, and GCF scores were able to distinguish patients with Clinical Dementia Rating of 0.5 and 1. Test-retest reliability was high, with a correlation coefficient of 0.918 for AD, 0.999 for MCI, and 0.960 for NC. The GCF score significantly correlated with the Mini-Mental State Examination (MMSE). Through ROC-curve analysis, GCF scores were found to yield more accurate diagnoses than the MMSE. The SNSB-D is a valid, reliable tool for assessing the overall cognitive function, and can be used to monitor cognitive changes in patients with dementia.     

Cognitive decline in older Mexican Americans with diabetes

OBJECTIVE: To examine social, demographic and health factors associated with cognitive decline over a seven-year period among older Mexican Americans with diabetes. METHODS: A population-based sample of 808 noninstitutionalized Mexican Americans aged >65 years with diabetes who had a Mini-Mental State Examination (MMSE) >17 at baseline from the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE). Measurements included sociodemographics, diabetic treatment received (oral hypoglycemic or insulin), self-reported medical conditions, self-reported diabetes-related complications, high depressive symptoms and ADL limitations. RESULTS: The mean MMSE score at baseline was 25.3 + (SD=3.7). The rate of decline in cognitive function (MMSE) during the follow-up period was 0.37 point per year. Using general linear mixed models, we found that being male, and having high depressive symptoms and diabetic complications (kidney impairment, circulation problems or limb amputation) were factors significantly associated with greater declines in MMSE score over time. CONCLUSION: Circulation problems, kidney impairment and depression are the major factors associated with cognitive decline in older Mexican Americans with diabetes.     

Plasma levels of beta-amyloid (1-42) in Alzheimer's disease and mild cognitive impairment

We compared plasma levels of beta-amyloid 1-42 (pg/ml) found for 146 sporadic Alzheimer (AD) patients, 89 subjects with mild cognitive impairment (MCI) and 89 age-matched controls (CT). AD patients had significantly lower levels (38, 54, 52; p<0.01), unrelated to severity of the disease as assessed by MMSE score, age, sex or APOE4 status. Twenty cases investigated at two time points 18 months apart did not demonstrate further decreases. Thus, the reduction in beta-amyloid 1-42 may be a marker for AD status, specifically, a transition from normal status or MCI to AD, rather than a marker for neurodegenerative processes occurring in the disease.     

Diagnostic and Prognostic Value of Low Density Lipoprotein-Containing Circulating Immune Complexes in Atherosclerosis

Recently, it has been shown that increased level of LDL-containing circulating immune complexes (LDL-CIC) possess high diagnostic significance in clinically manifested atherosclerosis, but little is known about its diagnostic and prognostic significance in early atherosclerosis. Two-years prospective study was performed in 98 asymptomatic men aged 40–74. The rate of atherosclerosis progression was estimated by high-resolution B-mode ultrasonography as the increase in intima-media thickness (IMT) of common carotid arteries. The patients with elevated baseline levels of LDL-CIC were characterized by significantly higher levels of total and LDL cholesterol as well as significantly increased mean IMT of common carotid arteries. Among all baseline lipid parameters, only LDL-CIC and LDL cholesterol were contingent with the extent of early carotid atherosclerosis (p?=?0.042 and p?=?0.049, respectively) and had the highest levels of relative risk and odds ratio. During the follow up, significant IMT increase was registered in 53.1 % (n?=?52) patients, IMT significant reduction was observed in 21.4 % (n?=?21) patients. The increased levels of LDL-CIC, total serum cholesterol and LDL cholesterol had similar prognostic significance with the respect of atherosclerosis progression. The normal level of LDL-CIC (below than 16.0 μg/ml) was the only lipid parameter that predicted the absence of carotid atherosclerosis progression for two following years at prognostic value of 78.3 %. The results of the study allow assuming that LDL-CIC level may be employed not only as a marker of early atherosclerosis, but also has a sufficient prognostic value for clinical implications.     

Changes in the levels of plasma soluble fractalkine in patients with mild cognitive impairment and Alzheimer's disease

Soluble fractalkine plays a distinctive role in the inflammatory processes of the nervous system; however, the role of soluble fractalkine in Alzheimer's disease (AD) has not yet been investigated. In the present study, we evaluated the levels of plasma soluble fractalkine in patients with mild cognitive impairment (MCI), patients with AD and healthy controls. We also investigated the changes in the levels of plasma soluble fractalkine in patients with AD. A total of 102 patients with cognitive impairment, including 51 patients with MCI, 51 patients with AD, and 57 healthy control subjects, were enrolled in this study. The Mini-Mental Status Examination (MMSE) was used to evaluate the severity of cognitive impairment in patients with MCI and AD. The levels of plasma soluble fractalkine were measured using a specific enzyme-linked immunosorbent assay. There were significant group differences in the levels of plasma soluble fractalkine between the MCI, AD, and control groups. Post hoc analyses revealed significant differences between the MCI and control groups, the AD and control groups, and the MCI and AD groups. The level of plasma soluble fractalkine was significantly greater in the patients with mild to moderate AD than in the patients with severe AD. In addition, there was a positive correlation between MMSE score and plasma soluble fractalkine level in the patients with AD. This study provides preliminary evidence that soluble fractalkine is involved in the pathogenesis of AD.     

Behavioural and neuropsychological correlates of frontal lobe features in dementia

BACKGROUND: In order to characterize frontal lobe features and their behavioural and cognitive correlates across diagnostic categories, we performed a cross-sectional analysis of behavioural and neuropsychological data from a large, prospective Belgian study on behavioural and psychological signs and symptoms of dementia (BPSD). METHOD: Patients with probable Alzheimer's disease (AD) (n=170), frontotemporal dementia (FTD) (n=28), mixed dementia (MXD) (n=29) and dementia with Lewy bodies (DLB) (n=21) were included and underwent neuropsychological and behavioural assessment by means of a battery of tests and scales. Frontal lobe symptoms were quantified by means of the Middelheim Frontality Score (MFS). RESULTS: In AD (and to a lesser extent in MXD), MFS total scores were negatively correlated with scores on MMSE (Spearman: r=-0.36, p<0.001) and a Verbal Fluency Task (r=-0.38, p<0.001) and were associated with increased severity and frequency of psychosis (r=0.24, p<0.01), activity disturbances (r=0.44, p<0.001) and aggressiveness (r=0.43, p<0.001). In DLB, MFS total scores were negatively correlated with MMSE scores (r=-0.50, p=0.020). No associations were found in FTD patients. CONCLUSIONS: A cross-sectional analysis of frontal lobe features, behavioural characteristics and neuropsychological data demonstrated that, in AD (and to a lesser extent in MXD) patients, frontal lobe symptoms were associated with more pronounced cognitive deficits (of frontal origin), with increased severity and frequency of agitated and aggressive behaviour, and with increased severity of psychosis and depressive symptoms. Given the small sample sizes of the DLB and FTD patient groups, negative findings in these patient groups should be interpreted cautiously.     

Test sequence of CSF and MRI biomarkers for prediction of AD in subjects with MCI

Our aim was to identify the best diagnostic test sequence for predicting Alzheimer's disease (AD)-type dementia in subjects with mild cognitive impairment (MCI) using cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers. We selected 153 subjects with mild cognitive impairment from a multicenter memory clinic-based cohort. We tested the CSF beta amyloid (Aβ)1-42/tau ratio using enzyme-linked immunosorbent assay (ELISA) and hippocampal volumes (HCVs) using the atlas-based learning embeddings for atlas propagation (LEAP) method. Outcome measure was progression to AD-type dementia in 2 years. At follow-up, 48 (31%) subjects converted to AD-type dementia. In multivariable analyses, CSF Aβ1-42/tau and HCV predicted AD-type dementia regardless of apolipoprotein E (APOE) genotype and cognitive scores. Test sequence analyses showed that CSF Aβ1-42/tau increased predictive accuracy in subjects with normal HCV (p < 0.001) and abnormal HCV (p = 0.025). HCV increased predictive accuracy only in subjects with normal CSF Aβ1-42/tau (p = 0.014). Slope analyses for annual cognitive decline yielded similar results. For selection of subjects for a prodromal AD trial, the best balance between sample size and number of subjects needed to screen was obtained with CSF markers. These results provide further support for the use of CSF and magnetic resonance imaging biomarkers to identify prodromal AD.