Oliver Preische

Diagnostic Value of a Tablet-Based Drawing Task for Discrimination of Patients in the Early Course of Alzheimer’s Disease from Healthy Individuals

There is a considerable delay in the diagnosis of dementia, which may reduce the effectiveness of available treatments. Thus, it is of great interest to develop fast and easy to perform, non-invasive and non-expensive diagnostic measures for the early detection of cognitive impairment and dementia. Here we investigate movement kinematics between 20 patients with early dementia due to Alzheimers disease (eDAT), 30 patients with amnestic mild cognitive impairment (aMCI), and 20 cognitively healthy control (HC) individuals while copying a three-dimensional house using a digitizing tablet. Receiver-operating characteristic (ROC) curves and logistic regression analyzes have been conducted to explore whether alterations in movement kinematics could be used to discriminate patients with aMCI and eDAT from healthy individuals. Time-in-air (i.e., transitioning from one stroke to the next without touching the surface) differed significantly between patients with aMCI, eDAT, and HCs demonstrating an excellent sensitivity and a moderate specificity to discriminate aMCI subjects from normal elderly and an excellent sensitivity and specificity to discriminate patients affected by mild Alzheimers disease from healthy individuals. Time-on-surface (i.e., time while stylus is touching the surface) differed only between HCs and patients with eDAT but not between HCs and patients with aMCI. Furthermore, total-time (i.e., time-in-air plus time-on-surface) did not differ between patients with aMCI and early dementia due to AD. Modern digitizing devices offer the opportunity to measure a broad range of visuoconstructive abilities that may be used as a fast and easy to perform screening instrument for the early detection of cognitive impairment and dementia in primary care.

Erratum: Structural Ultrasound of the Medial Temporal Lobe in Alzheimer’s Disease

Purpose One of the anatomical hallmarks of Alzheimer’s disease (AD) is the atrophy of the medial temporal lobe (MTL), yet cost-effective and broadly available methodological alternatives to the current imaging tools for screening of this brain area are not currently available. Materials and Methods Using structural transcranial ultrasound (TCS), we attempted to visualize and measure the MTL, and compared the results of 32 AD patients and 84 healthy controls (HC). The MTL and the surrounding space were defined in the coronal plane on TCS. A ratio of the height of the MTL/height of the choroidal fissure (M/F) was calculated in order to obtain a regional proportion. Results An insufficient temporal bone window was identified in 22 % of the AD patients and 12 % of the HCs. The results showed that the ratio of M/F was significantly smaller in the AD group on both sides (p = 0.004 right, p = 0.007 left side). Furthermore, the M/F ratio made it possible to discriminate AD patients from HCs with a sensitivity of 83 % (right)/73 % (left) and a specificity of 76 % (right)/72 % (left) which is basically comparable to results published for magnetic resonance imaging. The measurements showed substantial intra/interrater reliability (ICC:0.79/0.69). Conclusion These results suggest that utilization of structural TCS may possibly constitute a cheap and easy-to-use supplement to other techniques for the diagnosis of AD. It may be especially useful as a screening tool in the large population of individuals with cognitive decline. Further studies are needed to validate this novel method.

Tau plasma levels in subjective cognitive decline: Results from the DELCODE study

Previous studies have demonstrated increased tau plasma levels in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) due to AD. Much less is known whether increased tau plasma levels can already be detected in the pre-MCI stage of subjective cognitive decline (SCD). In the present study we measured tau plasma levels in 111 SCD patients and 134 age- and gender-matched cognitively healthy controls participating in the DZNE (German Center for Neurodegenerative Diseases) longitudinal study on cognition and dementia (DELCODE). Tau plasma levels were measured using ultra-sensitive, single-molecule array (Simoa) technology. We found no significant different tau plasma levels in SCD (3.4 pg/ml) compared with healthy controls (3.6 pg/ml) after controlling for age, gender, and education (p = 0.137). In addition, tau plasma levels did not correlate with Aβ42 (r = 0.073; p = 0.634), tau (r = −0.179; p = 0.240), and p-tau181 (r = −0.208; p = 0.171) cerebrospinal fluid (CSF) levels in a subgroup of 45 SCD patients with available CSF. In conclusion, plasma tau is not increased in SCD patients. In addition, the lack of correlation between tau in plasma and CSF in the examined cohort suggests that tau levels are affected by different factors in both biofluids.

TAU PLASMA LEVELS IN SUBJECTIVE COGNITIVE DECLINE: RESULTS FROM THE DELCODE STUDY

Background: Alcadeina (Alca) is a member of alcadein family composed of Alca, Alcb and Alcg, which is largely expressed in brain neuron and prone to form a tripartite complex with APP mediated by cytoplasmic neural-specific adaptor protein X11like (X11L). p3-Alca is generated from Alca by cleavage of aand g-secretases, and secreted into cerebrospinal fluid (CSF) and then into blood as does Ab from APP. The p3-Alca35 exists in CSF as a major species, as like as Ab40, while p3-Alca38 is minor as like as Ab42. p3-Alca is non-aggregatable so easily detected in CSF and plasma by sELISA (Hata 2009). To establish an effective AD diagnosis, we verified p3-Alca38/35, a ratio of p3-Alca38 to p3-Alca35. Methods: Previously, we showed the plasma level of p3-Alca35 using sELISAwith p3-Alca35 specific antibody (Omori 2014). To measure p3-Alca38/35 level, we tried to prepare new antibody raised to p3-Alca38 with higher affinity. Using cell surface display method, p3-Alca38 chimeric protein was expressed on cell surface and the cells were immunized. Several clones generating antibody specifically react to p3Alca38 were isolated, and we developed new sELISA system to quantify p3-Alca38 with higher sensitivity. Results:We first characterized the new sELISA systems to quantify p3-Alca38. With a combination of sELISA to quantify p3-Alca35, both p3-Alca35 and p3-Alca38 in body fluid were quantified. The levels p3Alca38/35 ratio in MCI and AD subjects showed a tendency increasing along with cognitive impairment degree compared to non-demented controls. The p3-Alca38/35 ratio significantly increased along with the increase of Ab42/40 ratio in vitro, while in vivo, the significant increase of p3-Alca38/35 correlated with the significant decrease of Ab42/40. Conclusions:Our study suggested that p3-Alca38/35 can be an effective biomarker of AD not only in CSF but also in plasma, which indicates a qualitative change of g-secretase activity. Further studies with samples from various cohorts (for example, with chronologically chasing and taking samples) will be performed to confirm the efficiency of p3-Alca38/35 as a biomarker to find prodromal and/or early stage MCI/AD subjects who shows an altered/attenuated g-secretase activity.

Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease

Little is known about effects of physical activity (PA) in genetically driven early‐onset autosomal dominant Alzheimers disease (AD).

SERUM NEUROFILAMENT LIGHT CHAIN LEVELS ARE ASSOCIATED WITH CSF NEUROFILAMENT LIGHT CHAIN, COGNITIVE STATUS, AND DISEASE PROGRESSION IN AUTOSOMAL DOMINANT AD

BMI: body mass index; FGF21: fibroblast growth factor 21; HbA1C: Glycated hemoglobin A1C; HDL-C: high density lipoprotein cholesterol HOMA index: Homeostasis Model Assessment index; LDL-C: low density lipoprotein cholesterol; MoCA: Montreal cognitive assessment; SBP: systolic blood pressure. Oliver Preische, Stephanie A. Schultz, Anja Apel, Jens Kuhle, Brian A. Gordon, Guoqiao Wang, Eric McDade, Randall J. Bateman, John C. Morris, Tammie L. S. Benzinger, Mathias Jucker, Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany; Washington University in St. Louis School of Medicine, St. Louis, MO, USA; German Center for Neurodegenerative Diseases, Tuebingen, Germany; Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany; University Hospital Basel, Basel, Switzerland; Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; Washington University School of Medicine, St. Louis, MO, USA; Washington University School of Medicine, Saint Louis, MO, USA. Contact e-mail: saschultz@wustl.edu

Worries about Alzheimer's Disease and Subjective Cognitive Decline in Proxies of AD Patients and Controls

Objective: Subjective Cognitive Decline (SCD) is actually considered to be associated with an increased likelihood of future cognitive impairment and dementia. Much less is known about worries concerning Alzheimer’s disease (AD Worry) and their relation to SCD, SCD with worries (SCD+Worry) and objective cognitive performance. Methods: We examined the prevalence and relation of AD Worry, SCD and SCD+Worry along with cognitive measures (MMSE, DemTect) among 100 proxies of persons with AD and 119 age-, gender- and education-matched controls. Results: AD Worry, SCD and SCD+Worry were frequently present in proxies of persons with AD (64.0%/47.0%/21.0%) and controls (62.2%/51.3%/16.8%) without significant group differences concerning frequency of occurrence and cognitive measures. Among proxies of AD patients, AD Worry occurred more frequently in first degree relatives (sons/daughters; 76.5%) compared to spouses (45.5%; p=0.002). Proxies with AD Worry were significantly younger (58.9 years) than proxies with SCD+Worry (67.4 years; p=0.012). Proxies of AD patients with feelings of burden reported SCD (55.6%) significantly more frequently than proxies without feelings of burden (32.4%; p=0.025). Controls with AD Worry reported SCD+Worry (23.0%) significantly more frequently compared to controls without AD Worry (6.7%; p=0.021). In line with the latter result, there was a significant positive correlation between AD Worry and SCD+Worry (r=0.211, p=0.021) in the control sample. Conclusion: AD Worry is a widespread phenomenon within the examined cohorts of proxies of AD patients and controls. It is not associated with objective cognitive impairment. However, the higher presence of SCD+Worry in those controls who reported AD Worry and the higher presence of AD Worry among sons and daughters of AD patients compared to spouses indicate that AD Worry could be an early indicator of future cognitive impairment. Longitudinal studies examining larger samples are needed to further elucidate the potential association between AD Worry, SCD and future cognitive decline.