Increased Cerebrospinal Fluid Concentration of ZnT3 Is Associated with Cognitive Impairment in Alzheimer’s Disease

2020 ◽  
Vol 77 (3) ◽  
pp. 1143-1155
Author(s):  
Daniela Enache ◽  
Joana B. Pereira ◽  
Vesna Jelic ◽  
Bengt Winblad ◽  
Per Nilsson ◽  
...  

Background: Cognitive deficits arising in the course of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Parkinson’s disease with dementia (PDD) are directly linked to synaptic loss. Postmortem studies suggest that zinc transporter protein 3 (ZnT3), AMPA glutamate receptor 3 (GluA3), and Dynamin1 are associated with cognitive decline in AD and Lewy body dementia patients. Objective: We aimed to evaluate the diagnostic value of ZnT3, GluA3, and Dynamin 1 in the cerebrospinal fluid (CSF) of patients with dementia due to AD, DLB, and PDD compared to cognitively normal subjective cognitive decline (SCD) patients in a retrospective study. In addition, we assessed the relationship between synaptic markers and age, sex, cognitive impairment, and depressive symptoms as well as CSF amyloid, phosphorylated tau (p-tau), and total tau (T-tau). Methods: Commercially available ELISA immunoassay was used to measure the levels of proteins in a total of 97 CSF samples from AD (N = 24), PDD (N = 18), DLB (N = 27), and SCD (N = 28) patients. Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE). Results: We found a significant increase in the concentrations of ZnT3, GluA3, and Dynamin1 in AD (p = 0.002) and of ZnT3 and Dynamin 1 in DLB (p = 0.001, p = 0.002) when compared to SCD patients. Changes in ZnT3 concentrations correlated with MMSE scores in AD (p = 0.011), and with depressive symptoms in SCD (p = 0.041). Conclusion: We found alteration of CSF levels of synaptic proteins in AD, PDD, and DLB. Our results reveal distinct changes in CSF concentrations of ZnT3 that could reflect cognitive impairment in AD with implications for future prognostic and diagnostic marker development.

2017 ◽  
Vol 29 (7) ◽  
pp. 1123-1135 ◽  
Author(s):  
J. Lehrner ◽  
G. Coutinho ◽  
P. Mattos ◽  
D. Moser ◽  
M. Pflüger ◽  
...  

ABSTRACTBackground:Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment.Methods:323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated.Results:Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS.Conclusions:We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.


2018 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Jiri Cerman ◽  
Ross Andel ◽  
Jan Laczo ◽  
Martin Vyhnalek ◽  
Zuzana Nedelska ◽  
...  

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.


2021 ◽  
Author(s):  
Noel Valencia ◽  
Johann Lehrner

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 157-158
Author(s):  
Benjamin Olivari ◽  
Christopher Taylor ◽  
Nia Reed ◽  
Lisa McGuire

Abstract Alzheimer’s disease and related dementias often begin with symptoms of mild memory loss, eventually leading to more severe cognitive impairment, functional impairment, and ultimately, death. Data from the Behavioral Risk Factor Surveillance System core questions related to chronic diseases and from the cognitive decline optional module on subjective cognitive decline (SCD) from the years 2015-2018 were aggregated across the participating 50 states, D.C., and Puerto Rico for this analysis. Among U.S. adults aged 65 years and older, only 39.8% (95%CI=37.6-42.1) of those experiencing SCD reported discussing their SCD symptoms with a healthcare provider. The prevalence of discussing SCD symptoms with a provider was higher among those with at least one chronic condition than among those with no chronic conditions. 30.7% (28.6-32.8) of those aged 65 years and older reported that their SCD led to functional limitations and 28.8% (26.5-31.2) needed assistance with day-to-day activities. For patients aged 65 years and older, Welcome to Medicare visits and Medicare Annual Wellness Visits are critically underutilized primary care access points. Primary care providers can manage chronic conditions, cognitive health, and initiate referrals for testing. Efforts to promote the use of toolkits and diagnostic codes that are available to primary care providers to initiate conversations about memory loss with patients may be utilized to improve detection, diagnosis, and planning for memory problems. Discussions may lead to earlier detection and diagnosis of cognitive impairment, such as Alzheimer’s disease, or other treatable conditions such as delirium or pressure in the brain and avoid costly hospitalizations.


2017 ◽  
Vol 29 (6) ◽  
pp. 1105-1111 ◽  
Author(s):  
Mehmet Yuruyen ◽  
Fundan Engin Akcan ◽  
Gizem Cetiner Batun ◽  
Gozde Gultekin ◽  
Mesut Toprak ◽  
...  

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.


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