scholarly journals Association of CSF Aβ38 Levels With Risk of Alzheimer Disease–Related Decline

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013228
Author(s):  
Nicholas Cullen ◽  
Shorena Janelidze ◽  
Sebastian Palmqvist ◽  
Erik Stomrud ◽  
Niklas Mattsson-Carlgren ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Lower Risk ◽  
Clinical Evidence ◽  
Cox Regression ◽  
Experimental Studies ◽  
Subjective Cognitive Decline ◽  
Linear Mixed Effects ◽  
State Examination

Objective:Experimental studies suggest that the balance between short and long Aβ species might modulate the toxic effects of Aβ in Alzheimer’s disease (AD) but clinical evidence is lacking. We studied whether Aβ38 levels in cerebrospinal fluid (CSF) relate to risk of AD dementia and cognitive decline.Methods:CSF Aβ38 levels were measured in 656 individuals across two clinical cohorts – the Swedish BioFINDER study and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cox regression models were used to evaluate the association between baseline Aβ38 levels and risk of AD dementia in AD-biomarker positive individuals (AD+; determined by CSF P-tau/Aβ42 ratio) with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Linear mixed effects models were used to evaluate the association between baseline Aβ38 levels and cognitive decline as measured by the Mini-Mental State Examination (MMSE) in AD+ participants with SCD, MCI or AD dementia.Results:In the BioFINDER cohort, high Aβ38 levels were associated with slower decline in MMSE (β = 0.30 points / sd., P = 0.001) and with lower risk of conversion to AD dementia (HR = 0.83 per sd., P = 0.03). In the ADNI cohort, higher Aβ38 levels were associated with less decline in MMSE (β = 0.27, P = 0.01), but not risk of conversion to AD dementia (P = 0.66). Aβ38 levels in both cohorts were significantly associated with both cognitive and clinical outcomes when further adjusted for CSF P-tau or CSF Aβ42 levels.Interpretation:Higher CSF Aβ38 levels are associated with lower risk of AD-related changes in two independent clinical cohorts. These findings suggest that γ-secretase modulators could be effective as disease-altering therapy.

scholarly journals CSF Aβ38 levels are associated with Alzheimer-related decline: implications for γ-secretase modulators

2021 ◽  
Author(s):  
Nicholas C. Cullen ◽  
Shorena Janelidze ◽  
Sebastian Palmqvist ◽  
Erik Stomrud ◽  
Niklas Mattsson-Carlgren ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Lower Risk ◽  
Regression Models ◽  
Cox Regression ◽  
Mixed Effects Models ◽  
Subjective Cognitive Decline ◽  
Linear Mixed Effects Models ◽  
Linear Mixed Effects

AbstractObjectiveShorter Aβ species might modulate disease progression in Alzheimer’s disease (AD). Here we studied whether Aβ38 levels in cerebrospinal fluid (CSF) are associated with risk of developing AD dementia and cognitive decline.MethodsCSF Aβ38 levels were measured in 656 individuals across two clinical cohorts – the Swedish BioFINDER study and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cox regression models were used to evaluate the association between baseline Aβ38 levels and risk of AD dementia in AD-biomarker positive individuals (AD+; determined by CSF P-tau/Aβ42 ratio) with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Linear mixed effects models were used to evaluate the association between baseline Aβ38 levels and cognitive decline as measured by MMSE in AD+ participants with SCD, MCI or AD dementia.ResultsIn the BioFINDER cohort, high Aβ38 levels were associated with slower decline in MMSE (β = 0.30 points / sd., P = 0.001) and with lower risk of conversion. To AD dementia (HR = 0.83 per sd., P = 0.03). In the ADNI cohort, higher Aβ38 levels were associated with less decline in MMSE (β = 0.27, P = 0.01), but not risk of conversion to AD dementia (P = 0.66). Aβ38 levels in both cohorts remained significantly associated with both outcomes when adjusted for CSF P-tau levels and remained associated with cognition when adjusted for CSF Aβ42 levels.ConclusionsHigher CSF Aβ38 levels are associated with lower risk of AD-related changes in two independent clinical cohorts. These findings may have implications for γ-secretase modulators as potential disease-altering therapy.

Subjective Spatial Navigation Complaints - A Frequent Symptom Reported by Patients with Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease

2018 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Jiri Cerman ◽  
Ross Andel ◽  
Jan Laczo ◽  
Martin Vyhnalek ◽  
Zuzana Nedelska ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Spatial Navigation ◽  
Subjective Cognitive Decline ◽  
Great Effort ◽  
Frequent Symptom ◽  
Normal Controls

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.

scholarly journals Assessing visuo-constructive functions in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease with the Vienna Visuo-Constructional Test 3.0 (VVT 3.0)

2021 ◽  
Author(s):  
Noel Valencia ◽  
Johann Lehrner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Multinomial Logistic Regression ◽  
Subjective Cognitive Decline ◽  
Healthy Controls ◽  
Considerable Potential ◽  
Multinomial Logistic Regression Analysis

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.

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Jairo E. Martinez ◽  
Enmanuelle Pardilla-Delgado ◽  
Edmarie Guzmán-Vélez ◽  
Clara Vila-Castelar ◽  
Rebecca Amariglio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Decline ◽  
Verbal Memory ◽  
Autosomal Dominant ◽  
Memory Performance ◽  
Subjective Cognitive Decline ◽  
Mutation Carriers ◽  
Study Partner

Abstract Objective: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance. Methods: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Results: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Conclusions: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

scholarly journals Promoting Conversations About Cognitive Decline Between Older Adults and Primary Care Providers

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 157-158
Author(s):  
Benjamin Olivari ◽  
Christopher Taylor ◽  
Nia Reed ◽  
Lisa McGuire
Keyword(s):  
Alzheimer’S Disease ◽  
Primary Care ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Chronic Conditions ◽  
Memory Loss ◽  
Primary Care Providers ◽  
Subjective Cognitive Decline ◽  
Care Providers

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.

Alexithymia in people with subjective cognitive decline, mild cognitive impairment, and mild Alzheimer’s disease

2017 ◽  
Vol 29 (6) ◽  
pp. 1105-1111 ◽  
Author(s):  
Mehmet Yuruyen ◽  
Fundan Engin Akcan ◽  
Gizem Cetiner Batun ◽  
Gozde Gultekin ◽  
Mesut Toprak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

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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