IC-P-010: COMPARING CEREBRAL WHITE MATTER, CEREBELLAR, AND PONTINE REFERENCE REGIONS TO CHARACTERIZE FLORBETAPIR PET MEASUREMENTS OF AMYLOID-β BURDEN IN PSEN1 E280A MUTATION CARRIERS AND NONCARRIERS FROM THE COLOMBIAN AUTOSOMAL DOMINANT ALZHEIMER'S DISEAS

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focussed on free-water corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.

Download Full-text

The Latin American Spanish version of the Face-Name Associative Memory Exam is sensitive to cognitive and pathological changes in preclinical autosomal dominant Alzheimer’s disease

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00671-w ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Clara Vila-Castelar ◽

Nathalia Muñoz ◽

Kathryn V. Papp ◽

Rebecca E. Amariglio ◽

Ana Baena ◽

...

Keyword(s):

Latin American ◽

Autosomal Dominant ◽

Amyloid Β ◽

Mutation Carriers ◽

Autosomal Dominant Alzheimer’S Disease ◽

The Face ◽

Latin American Spanish ◽

American Spanish ◽

Age Range ◽

Cognitively Intact

Abstract Background To determine whether performance on the Latin American Spanish version of the Face-Name Associative Memory Exam (LAS-FNAME) can differentiate between cognitively intact carriers of an autosomal dominant Alzheimer’s disease mutation (E280A) in Presenilin-1, who are genetically determined to develop early-onset dementia, from matched non-carriers. We also sought to examine whether LAS-FNAME performance is associated with amyloid-β and regional tau burden in mutation carriers. Methods A total of 35 cognitively intact mutation carriers (age range 26–41), 19 symptomatic carriers, and 48 matched non-carriers (age range 27–44) completed a neuropsychological assessment including the LAS-FNAME. A subset of participants (31 carriers [12 symptomatic] and 35 non-carriers) traveled from Colombia to Boston to undergo positron emission tomography (PET) using Pittsburgh compound B to measure mean cortical amyloid-β and flortaucipir for regional tau. ANOVA analyses and Spearman correlations were used to examine group differences and relationships among LAS-FNAME performance and amyloid-β and tau accumulation. Results Compared to non-carriers, cognitively intact mutation carriers had lower scores on the LAS-FNAME Total Scores (p = .040). Across all carriers (including symptomatic carriers), higher levels of amyloid-β (r = − .436, p = .018) and regional tau in the entorhinal (r = − .394, p = .031) and inferior temporal cortex (r = − .563, p = .001) were associated with lower LAS-FNAME Total Scores. Conclusions Performance on the LAS-FNAME differentiated between cognitively intact mutation carriers from non-carriers and was associated with greater amyloid and tau burden when examining all carriers. Findings suggest that the LAS-FNAME is sensitive to early clinical and pathological changes and can potentially help track disease progression in Spanish-speaking individuals.

Download Full-text

Association of Plasma Oligomerized Amyloid-β and Cerebral White Matter Lesions in a Health Screening Population

Journal of Alzheimer s Disease ◽

10.3233/jad-215399 ◽

2021 ◽

pp. 1-10

Author(s):

Keun-Hwa Jung ◽

Kyung-Il Park ◽

Woo-Jin Lee ◽

Hyo-Shin Son ◽

Kon Chu ◽

...

Keyword(s):

White Matter ◽

Amyloid Β ◽

White Matter Lesions ◽

Health Screening ◽

Magnetic Resonance Images ◽

Cerebral White Matter ◽

Clinical Dementia Rating ◽

Cerebral White Matter Lesions ◽

Screening Population ◽

Periventricular Area

Background: Cerebral white matter lesions (WML) are related to a higher risk of vascular and Alzheimer’s dementia. Moreover, oligomerized amyloid-β (OAβ) can be measured from blood for dementia screening. Objective: We aimed to investigate the relationship of plasma OAβ levels with clinical and radiological variables in a health screening population. Methods: WML, other volumetric parameters of magnetic resonance images, cognitive assessment, and plasma OAβ level were evaluated. Results: Ninety-two participants were analyzed. The majority of participants’ clinical dementia rating was 0 or 0.5 (96.7%). White matter hyperintensities (WMH) increased with age, but OAβ levels did not (r2 = 0.19, p < 0.001, r2 = 0.03, p = 0.10, respectively). No volumetric data, including cortical thickness/hippocampal volume, showed any significant correlation with OAβ. Log-WMH volume was positively correlated with OAβ (r = 0.24, p = 0.02), and this association was significant in the periventricular area. White matter signal abnormalities from 3D-T1 images were also correlated with the OAβ in the periventricular area (p = 0.039). Multivariate linear regression showed that log-WMH values were independently associated with OAβ (B = 0.879 (95% confidence interval 0.098 –1.660, p = 0.028)). Higher tertiles of WMH showed higher OAβ levels than lower tertiles showed (p = 0.044). Using a cutoff of 0.78 ng/mL, the high OAβ group had a larger WMH volume, especially in the periventricular area, than the low OAβ group (p = 0.036). Conclusion: Both WML and plasma OAβ levels can be early markers for neurodegeneration in the healthcare population. The lesions, especially in the periventricular area, might be related to amyloid pathogenesis, which strengthens the importance of WML in the predementia stage.

Download Full-text

Arterial Changes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Relation to Pathogenesis of Diffuse Myelin Loss of Cerebral White Matter

Stroke ◽

10.1161/01.str.0000032620.91848.1c ◽

2002 ◽

Vol 33 (11) ◽

pp. 2565-2569 ◽

Cited By ~ 76

Author(s):

Riki Okeda ◽

Kunimasa Arima ◽

Mitsuru Kawai

Keyword(s):

White Matter ◽

Autosomal Dominant ◽

Cerebral White Matter

Download Full-text

18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

10.21203/rs.3.rs-188622/v1 ◽

2021 ◽

Author(s):

Alexis Moscoso ◽

Jesus Silva-Rodriguez ◽

Jose Manuel Aldrey ◽

Julia Cortes ◽

Juan Manuel Pias-Peleteiro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Diffusion Tensor ◽

Amyloid Β ◽

Cerebral White Matter ◽

Csf Biomarkers ◽

Cognitively Impaired ◽

Disease Course ◽

Clinical Progression

Abstract Purpose: Recent evidence suggest that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer’s disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored.Methods: Participants with concurrent 18F-florbetapir (FBP), MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n=195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and CSF biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. Results: In AD-continuum individuals, FBP retention in NAWM was 1) higher compared to WMH regions, 2) associated with DTI-based measures of WM integrity, and 3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals.Conclusion: These results support the hypothesis that FBP retention in the WM is myelin-dependent. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.

Download Full-text

18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05493-y ◽

2021 ◽

Author(s):

Alexis Moscoso ◽

Jesús Silva-Rodríguez ◽

Jose Manuel Aldrey ◽

Julia Cortés ◽

Juan Manuel Pías-Peleteiro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Diffusion Tensor ◽

Amyloid Β ◽

Cerebral White Matter ◽

Csf Biomarkers ◽

Cognitively Impaired ◽

Disease Course ◽

Clinical Progression

Abstract Purpose Recent evidence suggests that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer’s disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored. Methods Participants with concurrent 18F-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n = 195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and fluid biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. Results In AD-continuum individuals, FBP retention in NAWM was (1) higher compared with WMH regions, (2) associated with DTI-based measures of WM integrity, and (3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals. Conclusion These results support the hypothesis that FBP retention in the WM is myelin-related. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.

Download Full-text

A-05 The Latin American Spanish Version of the Face-Name Associative Memory Exam is Sensitive to Cognitive and Pathological Changes in Preclinical Autosomal Dominant Alzheimer’s Disease

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acaa067.05 ◽

2020 ◽

Vol 35 (6) ◽

pp. 778-778

Author(s):

C Vila-Castelar ◽

N Muñoz ◽

K Papp ◽

R Amariglio ◽

A Baena ◽

...

Keyword(s):

Latin American ◽

Autosomal Dominant ◽

Amyloid Β ◽

Pathological Changes ◽

Mutation Carriers ◽

Autosomal Dominant Alzheimer’S Disease ◽

The Face ◽

Latin American Spanish ◽

American Spanish ◽

Cognitively Intact

Abstract Objective To determine whether performance on the Latin American Spanish version of the Face-Name Associative Memory Exam (LAS-FNAME) can differentiate between cognitively intact carriers of an autosomal dominant Alzheimer’s disease mutation (E280A) in Presenilin-1, who are destined to develop early-onset dementia, from matched non-carriers. We also sought to examine whether LAS-FNAME performance is associated with amyloid-β and regional tau burden in mutation carriers. Methods 35 cognitively intact mutation carriers (age range 26–41), 48 matched non-carriers (aged 27 to 44), and 19 symptomatic carriers (13 with subjective cognitive concerns, 6 with mild cognitive impairment [MCI]) completed the LAS-FNAME. A subset of participants (31 carriers [12 symptomatic] and 35 non-carriers) traveled from Colombia to Boston to undergo positron emission tomography (PET) using Pittsburgh compound B to measure mean cortical amyloid-β and Flortaucipir for regional tau tangles. ANOVA analyses and Spearman correlations were used to examine group differences and relationships among LAS-FNAME performance, Aβ and tau accumulation. Results Compared to non-carriers, cognitively intact carriers had lower scores on the LAS-FNAME total scores (p = .040). Across all carriers (including symptomatic carriers), higher levels of amyloid-β (r = −.436, p = .018) and regional tau in the entorhinal (r = −.394, p = .031) and inferior temporal cortex (r = −.563, p = .001) were associated with lower LAS-FNAME total scores (see Figure). Conclusions Performance on the LAS-FNAME differentiated between cognitively intact mutation carriers from non-carriers, and was associated with greater amyloid and tau burden when examining all carriers. Findings suggest that the LAS-FNAME is sensitive to early clinical and pathological changes and can potentially help track disease progression in Spanish-speaking individuals.

Download Full-text