Evidence for Reduced Autobiographical Memory Episodic Specificity in Cognitively Normal Middle-Aged and Older Individuals at Increased Risk for Alzheimer’s Disease Dementia

AbstractObjectives: Alzheimer’s disease (AD) typically eludes clinical detection for years, if not decades. The identification of subtle cognitive decline associated with preclinical AD would not only advance understanding of the disease, but also provide clinical targets to assess preventative and early intervention treatments. Disrupted retrieval of detailed episodic autobiographical memories may be a sensitive indicator of subtle cognitive decline, because this type of memory taxes a core neural network affected by preclinical AD neuropathology. Methods: To begin to address this idea, we assessed the episodic specificity of autobiographical memories retrieved by cognitively normal middle-aged and older individuals who are carriers of the apolipoprotein E ε4 allele – a population at increased risk for subtle cognitive decline related to neuropathological risk factors for AD. We compared the ε4 carriers to non-carriers of ε4 similar in age, education, and gender. Results: The ε4 carriers did not perform worse than the non-carriers on a comprehensive battery of neuropsychological tests. In contrast, as a group, the ε4 carriers generated autobiographical memories that were reduced in “internal” or episodic details relative to non-carriers. Conclusions: These findings support the notion that reduced autobiographical episodic detail generation may be a marker of subtle cognitive decline associated with AD. (JINS, 2018, 24, 1073–1183)

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Regional atrophy and cognitive decline depend on definition of subjective cognitive decline

10.1101/2021.04.21.21255752 ◽

2021 ◽

Author(s):

Cassandra Morrison ◽

Mahsa Dadar ◽

Neda Shafiee ◽

Sylvia Villeneuve ◽

D. Louis Collins ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Cognitive Change ◽

Disease Assessment ◽

Subjective Cognitive Decline ◽

Cognitively Normal ◽

Increased Risk ◽

Definition Of

AbstractBackgroundPeople with subjective cognitive decline (SCD) may be at increased risk for Alzheimer’s disease (AD). However, not all studies have observed this increased risk. Inconsistencies may be related to different methods used to define SCD. The current project examined whether four methods of defining SCD (applied to the same sample) results in different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+) and without SCD (SCD-).MethodsMRI scans and questionnaire data for 273 cognitively normal older adults from Alzheimer’s Disease Neuroimaging Initiative were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry only. A previously validated MRI analysis method (SNIPE) was used to measure hippocampal volume and grading. Deformation-based morphometry was performed to examine volume at regions known to be vulnerable to AD. Logistic regressions were completed to determine whether diagnostic method was associated with volume differences between SCD- and SCD+. Linear mixed effects models were performed to examine the relationship between the definitions of SCD and future cognitive decline.ResultsResults varied between the four methods of defining SCD. Left hippocampal grading was lower in SCD+ than SCD-when using the CCI (p=.041) and Worry (p=.021) definitions. The right (p=.008) and left (p=.003) superior temporal regions were smaller in SCD+ than SCD-, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer’s Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment.ConclusionThe current findings suggest that the various methods used to differentiate between SCD- and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.

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Association of Subjective Cognitive Decline with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study

Journal of Alzheimer s Disease ◽

10.3233/jad-215178 ◽

2021 ◽

pp. 1-9

Author(s):

Chen Wen ◽

Yan-Lin Bi ◽

Hao Hu ◽

Shu-Yi Huang ◽

Ya-Hui Ma ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Decline ◽

Subjective Cognitive Decline ◽

Csf Biomarkers ◽

Cognitively Normal ◽

Normal Individuals ◽

Increased Risk ◽

T Tau

Background: Subjective cognitive decline (SCD) might occur at the early stages of dementia. Individuals with SCD have an increased risk of subsequent objective cognitive decline and greater rates of progression to dementia. Objective: We aimed to explore the associations between SCD and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in cognitively normal individuals. Methods: A total of 1,099 cognitively normal elders with available data on CSF biomarkers of AD pathology (Aβ 42, P-tau, and T-tau) were included in our analysis. Linear regression was used to examine the associations of SCD status and SCD severity with CSF biomarkers. Additionally, a review was conducted to discuss the associations between SCD and CSF biomarkers of AD pathology. Results: After adjustments for covariates, SCD and SCD severity showed significant associations with CSF Aβ 42 (SCD: β= –0.0003, p = 0.0263; SCD severity: β= –0.0004, p = 0.0046), CSF T-tau/Aβ 42 ratio (SCD: β= 0.1080, p = 0.1080; SCD severity: β= 0.1129, p = 0.0009) and CSF P-tau/Aβ 42 ratio (SCD: β= 0.0167, p = 0.0103; SCD severity: β= 0.0193, p = 0.0006) rather than T-tau and P-tau compared with cognitively normal individuals. In the review, a total of 28 studies were finally included after reviewing 174 articles. CSF Aβ 42 was lower in SCD than cognitively normal (CN) individuals, but higher than those with objective cognitive decline. However, CSF tau pathology showed no difference between SCD and CN. Conclusion: The results indicated that pathophysiological changes in CSF Aβ pathology occurred in individuals with SCD, which provide new insights into early intervention of AD.

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Subtle Cognitive Decline predicts progression to Mild Cognitive Impairment Above and Beyond Alzheimer’s Disease Risk Factors

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acz035.14 ◽

2019 ◽

Vol 34 (6) ◽

pp. 846-846

Author(s):

J Osuna ◽

K Thomas ◽

E Edmonds ◽

K Bangen ◽

A Weigand ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Disease Risk ◽

Preclinical Ad ◽

Increased Risk

Abstract Objective Early identification of those at risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is critical for early intervention. Recent work shows that subtle cognitive decline (SCD), operationally-defined using sensitive neuropsychological scores, predicts progression to MCI/AD and is associated with AD biomarkers. We aimed to determine whether SCD adds unique value in predicting progression to MCI/AD above and beyond other AD risk factors. Method 547 cognitively unimpaired participants from the Alzheimer’s Disease Neuroimaging Initiative (359 without SCD; 188 with SCD) underwent neuropsychological testing and lumbar puncture. Participants were classified as SCD if they performed >1 SD below the demographically-adjusted mean on 1) two neuropsychological total scores in different cognitive domains, or 2) two memory test process scores (e.g., intrusion errors), or 3) one total score and one process score. Cox regressions examined whether SCD status predicted progression to MCI and AD within 5 years after adjusting for age, education, sex, MMSE, depressive symptoms, ischemia risk, apolipoprotein E genotype, and AD biomarker “positivity” based on the cerebrospinal fluid phosphorylated tau-to-β-amyloid ratio. Results SCD status predicted progression to MCI (HR = 2.74, 95% CI = 2.07-3.63, p < .001) and AD (HR = 2.20, 95% CI = 1.04-4.65, p = .04) within 5 years, even after including known AD risk factors in the model. Conclusion SCD conveys a 2-3 fold increased risk of progression to MCI/AD and is a unique predictor above and beyond risk factors that are commonly used in preclinical AD research. These findings support our novel SCD criteria as a cost-effective and non-invasive method for identifying those at risk for future cognitive decline.

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Association of Sleep Disturbance With Longitudinal Cognitive Decline Among Cognitively Normal Elders

10.21203/rs.3.rs-149162/v1 ◽

2021 ◽

Author(s):

Wei Feng ◽

Mandela William Nzoyoum Kuetche ◽

Meng Zhang ◽

Mengmeng Liu ◽

Yue Liu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Sleep Disturbance ◽

Cox Regression ◽

Significant Risk ◽

Marginal Effect ◽

Cognitively Normal ◽

Cox Regression Analysis ◽

Increased Risk

Abstract Background: A lot of evidence demonstrated sleep disturbance (SD) gets associated with Alzheimer’s disease (AD), but whether or not sleep disturbance could be the preclinical stage of AD is still unknown.Objective: 463 cognitively normal elders (357 normal and 106 SD) in baseline with cognitive and biomarker data were included in the study. Participants were collected from 2005 to 2020 (16 years follow-up) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).Methods: A generalized linear mixed model was used to adjust time variables and other covariates selected by the Akaike Information Criterion (AIC). Besides, the marginal effect estimation method was used to evaluate the interaction between sleep disturbance and time on cognitive decline. Cox regression was used to assess the survival risk of AD in sleep disturbance.Results: The age range of participants was 73.60±5.71 years old, and the female proportion was 43.63%. Taking time as a continuous variable in longitudinal analyses, it was found that sleep disturbance had a significant long-term negative effect on MMSE, PACC, CSF Aβ, and ventricular volume (P<0.05). Cox regression analysis showed that sleep disturbance is a significant risk factor of AD (HR=1.55, 95% CI=1.08 to 2.22).Conclusion: Sleep disturbance in baseline was associated with subsequent cognitive decline among cognitively normal elders and is an increased risk of AD, which means sleep disturbance could probably be the pre-symptomatic stage of AD.

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

Dementia & Neuropsychologia ◽

10.1590/s1980-5764-2016dn1003002 ◽

2016 ◽

Vol 10 (3) ◽

pp. 170-177 ◽

Cited By ~ 22

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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The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2020.625844 ◽

2021 ◽

Vol 14 ◽

Author(s):

Dong-Yu Fan ◽

Hao-Lun Sun ◽

Pu-Yang Sun ◽

Jie-Ming Jian ◽

Wei-Wei Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Plasma Fibrinogen ◽

Cognitively Normal ◽

Amyloid Aβ ◽

And Gender ◽

T Tau ◽

The Relationship ◽

Phosphorylated Tau 181 ◽

Normal Controls

Recent studies show that fibrinogen plays a role in the pathogenesis of Alzheimer’s disease (AD), which may be crucial to neurovascular damage and cognitive impairment. However, there are few clinical studies on the relationship between fibrinogen and AD. 59 11C-PiB-PET diagnosed AD patients and 76 age- and gender-matched cognitively normal controls were included to analyze the correlation between plasma β-amyloid (Aβ) and tau levels with fibrinogen levels. 35 AD patients and 76 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation between CSF Aβ and tau levels with fibrinogen levels. In AD patients, plasma fibrinogen levels were positively correlated with plasma Aβ40 and Aβ42 levels, and negatively correlated with CSF Aβ42 levels. Besides, fibrinogen levels were positively correlated with CSF total tau (t-tau), and phosphorylated tau-181 (p-tau) levels and positively correlated with the indicators of Aβ deposition in the brain, such as t-tau/Aβ42, p-tau/Aβ42 levels. In normal people, fibrinogen levels lack correlation with Aβ and tau levels in plasma and CSF. This study suggests that plasma fibrinogen levels are positively correlated with Aβ levels in the plasma and brain in AD patients. Fibrinogen may be involved in the pathogenesis of AD.

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