scholarly journals Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

Author(s):  
Niels Hansen ◽  
Berend Malchow ◽  
Inga Zerr ◽  
Winfried Stöcker ◽  
Jens Wiltfang ◽  
...  

AbstractAutoantibody-associated cognitive impairment is an expanding field in geriatric psychiatry. We aim to assess the association between the presence of specific neural autoantibodies and cognitive performance in a memory clinic cohort. 154 patients with cognitive impairment were included between 2019 and 2020 presenting initially in a memory clinic. We evaluated their patient files retrospectively applying epidemiologic parameters, psychopathology, neuropsychology, intracellular and membrane-surface autoantibodies in serum and cerebrospinal fluid (CSF) and markers of neurodegeneration in CSF. In 26 of 154 patients, we searched for neural autoantibodies due to indicators for autoimmunity. In 15/26 (58%) of patients we detected serum and/or CSF autoantibodies. We identified autoantibodies against intracellular or cell-surface antigens in 7 of all 26 (27%) patients with cognitive dysfunction, although we cannot exclude patients with potential specific autoantibodies lacking autoimmune indicators. There were no significant differences between psychopathological and neuropsychological profiles in groups of patients with cognitive impairment comprising patients with autoantibodies (ABS + COG), no autoantibodies (ABS − COG), and Alzheimer’s disease (ADCOG). Concerning our CSF parameters, we detected intrathecal IgG synthesis in 14% of ABS + COG and in 13% of ABS − COG patients, whereas no intrathecal IgG synthesis was found in ADCOG patients. Furthermore, CSF Aß42 was significantly diminished in the ADCOG compared to the ABS + COG group (p < 0.05). In addition, the Aß42/40 ratio was lower in ADCOG patients than in the ABS + COG or ABS − COG group (p < 0.05). Our findings reveal the underestimated occurrence and autoantibodies’ potential role in patients presenting cognitive impairment. Furthermore, the patients with possible Alzheimer’s disease might be differentiated from autoantibody-positive patients via a reduced Aß42 and Aß42/40 ratio in the CSF. The antibody-type varies between patients to a relevant degree, thus demonstrating the need for more research to identify subgroup-specific phenotypes. These pilot study results open an avenue for improving diagnosis and treatment in a memory clinic.

2020 ◽  
pp. 1-14
Author(s):  
Yi-Wen Bao ◽  
Anson C.M. Chau ◽  
Patrick Ka-Chun Chiu ◽  
Yat Fung Shea ◽  
Joseph S.K. Kwan ◽  
...  

Background: With the more widespread use of 18F-radioligand-based amyloid-β (Aβ) PET-CT imaging, we evaluated Aβ binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. Objective: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer’s disease (AD), and 2) MCI from other non-AD dementias (OD). Methods: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). Results: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aβ binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. Conclusion: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.


2015 ◽  
Vol 36 (1) ◽  
pp. 114-131 ◽  
Author(s):  
Anders Wallin ◽  
Arto Nordlund ◽  
Michael Jonsson ◽  
Karin Lind ◽  
Åke Edman ◽  
...  

There is a need for increased nosological knowledge to enable rational trials in Alzheimer’s disease (AD) and related disorders. The ongoing Gothenburg mild cognitive impairment (MCI) study is an attempt to conduct longitudinal in-depth phenotyping of patients with different forms and degrees of cognitive impairment using neuropsychological, neuroimaging, and neurochemical tools. Particular attention is paid to the interplay between AD and subcortical vascular disease, the latter representing a disease entity that may cause or contribute to cognitive impairment with an effect size that may be comparable to AD. Of 664 patients enrolled between 1999 and 2013, 195 were diagnosed with subjective cognitive impairment (SCI), 274 with mild cognitive impairment (MCI), and 195 with dementia, at baseline. Of the 195 (29%) patients with dementia at baseline, 81 (42%) had AD, 27 (14%) SVD, 41 (21%) mixed type dementia (=AD + SVD = MixD), and 46 (23%) other etiologies. After 6 years, 292 SCI/MCI patients were eligible for follow-up. Of these 292, 69 (24%) had converted to dementia (29 (42%) AD, 16 (23%) SVD, 15 (22%) MixD, 9 (13%) other etiologies). The study has shown that it is possible to identify not only AD but also incipient and manifest MixD/SVD in a memory clinic setting. These conditions should be taken into account in clinical trials.


2017 ◽  
Vol 13 (7S_Part_23) ◽  
pp. P1145-P1145
Author(s):  
Bjørn-Eivind Kirsebom ◽  
Ragna Espenes ◽  
Knut Waterloo ◽  
Stein Harald Johnsen ◽  
Erik Hessen ◽  
...  

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 108
Author(s):  
Andrea Brugnolo ◽  
Nicola Girtler ◽  
Elisa Doglione ◽  
Beatrice Orso ◽  
Federico Massa ◽  
...  

Semantic cues in the Free and Cued Selective Reminding Test (FCRST) play a key role in the neuropsychological diagnosis of Amnesic Mild Cognitive Impairment due to Alzheimer’s Disease (MCI-AD); however, the neural bases of their impact of recall abilities are only partially understood. Here, we thus decided to investigate the relationships between brain metabolism and the FCSRT Index of Sensitivity of Cueing (ISC) in patients with MCI-AD and in healthy controls (HC). Materials: Thirty MCI-AD patients (age: 74.7 ± 5.7 years; education: 9.6 ± 4.6 years, MMSE score: 24.8 ± 3.3, 23 females) and seventeen HC (age: 66.5 ± 11.1 years; education: 11.53 ± 4.2 years, MMSE score: 28.4 ± 1.14, 10 females) who underwent neuropsychological evaluation and brain F-18 fluorodeoxyglucose Positron Emission Tomography (FDG-PET) were included in the study. Results: ISC was able to differentiate HC from MCI-AD subjects as shown by a ROC analysis (AUC of 0.978, effect size Hedges’s g = 2.89). MCI-AD subjects showed significant hypometabolism in posterior cortices, including bilateral inferior Parietal Lobule and Precuneus and Middle Temporal gyrus in the left hemisphere (VOI-1) compared to HC. ISC was positively correlated with brain metabolism in a single cluster (VOI-2) spanning the left prefrontal cortex (superior frontal gyrus) and anterior cingulate cortex (ACC) in the patient group (R2 = 0.526, p < 0.001), but not in HC. Mean uptake values of VOI-2 did not differ between HC and MCI-AD. The structural connectivity analysis showed that VOI-2 is connected with the temporal pole, the cingulate gyrus and the posterior temporal cortices in the left hemisphere. Conclusion: In MCI-AD, the relative preservation of frontal cortex metabolic levels and their correlation with the ISC suggest that the left frontal cortices play a significant role in maintaining a relatively good memory performance despite the presence of posterior hypometabolism in MCI-AD.


2016 ◽  
Vol 42 (3-4) ◽  
pp. 135-145 ◽  
Author(s):  
Jun Ho Lee ◽  
Min Soo Byun ◽  
Dahyun Yi ◽  
Young Min Choe ◽  
Hyo Jung Choi ◽  
...  

Aims: The aims of this study were to investigate the frequency of various depressive syndromes in elderly individuals with no cognitive impairment (NC), mild cognitive impairment (MCI), and Alzheimer's disease dementia (AD) in a memory clinic setting, and then to test whether severe and milder forms of depressive syndromes are differentially associated with the cognitive groups. Methods: For 216 NC, 478 MCI, and 316 AD subjects, we investigated the frequency of depressive syndromes, defined by three different categories: major and minor depressive disorder (MaDD and MiDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, as well as depression according to the National Institute of Mental Health provisional diagnostic criteria for depression in Alzheimer's disease (NIMH-dAD). Results: The frequency of MaDD did not show any significant difference among NC, MCI, and AD. In contrast, the frequencies of MiDD and NIMH-dAD were higher than those of MaDD and showed significant group differences with a gradual increase from NC to AD. Conclusion: The findings suggest that the degenerative process of Alzheimer's disease contributes to the occurrence of mild depressive conditions, but not to severe depression.


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