The Value of OCT and OCTA as Potential Biomarkers for Preclinical Alzheimer’s Disease: A Review Study

Preclinical Alzheimer’s disease (AD) includes cognitively healthy subjects with at least one positive biomarker: reduction in cerebrospinal fluid Aβ42 or visualization of cerebral amyloidosis by positron emission tomography imaging. The use of these biomarkers is expensive, invasive, and not always possible. It has been shown that the retinal changes measured by optical coherence tomography (OCT) and OCT-angiography (OCTA) could be biomarkers of AD. Diagnosis in early stages before irreversible AD neurological damage takes place is important for the development of new therapeutic interventions. In this review, we summarize the findings of different published studies using OCT and OCTA in participants with preclinical AD. To date, there have been few studies on this topic and they are methodologically very dissimilar. Moreover, these include only two longitudinal studies. For these reasons, it would be interesting to unify the methodology, make the inclusion criteria more rigorous, and conduct longer longitudinal studies to assess the evolution of these subjects. If the results were consistent across repeated studies with the same methodology, this could provide us with insight into the value of the retinal changes observed by OCT/OCTA as potential reliable, cost-effective, and noninvasive biomarkers of preclinical AD.

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Identifying Preclinical Alzheimer’s Disease Using Everyday Driving Behavior: Proof of Concept

Journal of Alzheimer s Disease ◽

10.3233/jad-201294 ◽

2020 ◽

pp. 1-6

Author(s):

Ganesh M. Babulal ◽

Ann Johnson ◽

Anne M. Fagan ◽

John C. Morris ◽

Catherine M. Roe

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Driving Behavior ◽

Amyloid Pet ◽

Preclinical Alzheimer’S Disease ◽

Neuropsychological Measures ◽

Receiver Operating Characteristic Curves ◽

Preclinical Ad ◽

Positron Emission

We examined whether driving behavior can predict preclinical Alzheimer’s disease (AD). Data from 131 cognitively normal older adults with cerebrospinal fluid (CSF) and/or positron emission tomography (PET) biomarkers were examined with naturalistic driving behavior. Receiver operating characteristic curves were used to predict the highest 10%, 25%, and 50% of values for CSF tau/Aβ42, ptau181/Aβ42, or amyloid PET. Six in vivo driving variables alone yielded area under the curves (AUC) from 0.64–0.82. Addition of age, Apolipoprotein ɛ4, and neuropsychological measures to the models improved the AUC (0.81 to 0.90). Driving can be used as novel neurobehavioral marker to identify presence of preclinical AD.

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Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer’s Disease

Journal of the International Neuropsychological Society ◽

10.1017/s1355617716000928 ◽

2016 ◽

Vol 22 (10) ◽

pp. 978-990 ◽

Cited By ~ 9

Author(s):

Emily C. Edmonds ◽

Katherine J. Bangen ◽

Lisa Delano-Wood ◽

Daniel A. Nation ◽

Ansgar J. Furst ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Standardized Uptake Value ◽

Imaging Biomarkers ◽

Preclinical Alzheimer’S Disease ◽

Preclinical Ad ◽

Novel Approach ◽

Positron Emission ◽

Subcortical Regions ◽

Cortical Regions

AbstractObjectives: We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods: A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results: Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions: Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. (JINS, 2016, 22, 978–990)

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Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

Scientific Reports ◽

10.1038/s41598-021-83585-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Soo Hyun Cho ◽

Sookyoung Woo ◽

Changsoo Kim ◽

Hee Jin Kim ◽

Hyemin Jang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Progression ◽

Disease Assessment ◽

Time Interval ◽

Disease Course ◽

Preclinical Alzheimer’S Disease ◽

Apoe Ε4 ◽

Preclinical Ad ◽

Cognitive Subscale

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

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Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer’s Disease: Results from the Gothenburg H70 Birth Cohort Studies

Journal of Alzheimer s Disease ◽

10.3233/jad-200751 ◽

2021 ◽

Vol 79 (1) ◽

pp. 225-235

Author(s):

Maya Arvidsson Rådestig ◽

Johan Skoog ◽

Henrik Zetterberg ◽

Jürgen Kern ◽

Anna Zettergren ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cohort Studies ◽

Cognitive Performance ◽

Birth Cohort ◽

Population Based ◽

Tau Pathology ◽

Preclinical Alzheimer’S Disease ◽

Preclinical Ad

Background: We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.

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Preclinical Alzheimer's disease

Reviews in Clinical Gerontology ◽

10.1017/s095925981400001x ◽

2014 ◽

Vol 24 (2) ◽

pp. 117-121

Author(s):

P Gil-Gregorio ◽

R Yubero-Pancorbo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Diagnostic Criteria ◽

Stage I ◽

Disease Stage ◽

Synaptic Dysfunction ◽

Preclinical Alzheimer’S Disease ◽

Cerebral Amyloidosis ◽

Three Stages

SummaryRecently, diagnostic criteria for preclinical Alzheimer's disease have been proposed. These describe and define three stages of disease. Stage I is focused on asymptomatic cerebral amyloidosis. Stage II includes evidence of synaptic dysfunction and/or early degeneration. Finally, stage III of the disease is characterized by the beginning of cognitive decline.

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