O4‐01‐04: Amyloid in Dementia Associated With Familial Ftld: Not an Innocent Bystander

Naasan, Georges; Rosen, Howard J.; Rabinovici, Gil D.; Miller, Bruce L.; Elofson, Jon; Coppola, Giovanni; Karydas, Anna; Fong, Jamie; Seeley, William W.

doi:10.1016/j.jalz.2014.04.387

Cited by 2 publications

(2 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 Finally, our autopsy results showed that more than one-half of Aβ + nfvPPA/svPPA patients exhibit concomitant FTLD pathology, compared to only 6% of Aβ + lvPPA patients (see Fig 3), which is consistent with several case reports showing that positive Aβ biomarkers do not necessarily indicate that the clinical syndrome is primarily driven by AD pathology. [53][54][55] Previous reports have shown that ApoE4 allele was a risk factor for amyloid positivity but not for neuropathological diagnosis of AD in PPA patients. 12,23,25 This has potential clinical ramifications, as the increased a priori likelihood of detecting (comorbid) Aβ pathology in older patients and/or ApoE ε4 carriers should be considered when interpreting Aβ biomarkers in patients with PPA.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Bergeron

Gorno‐Tempini

Rabinovici

et al. 2018

Annals of Neurology

Self Cite

149

111

View full text Add to dashboard Cite

Objective: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebro-spinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. Methods: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models. Results: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE ε4 carriers were more often amyloid-β positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration–TDP-43 in svPPA (80%), and frontotemporal lobar degeneration–TDP-43/tau in nfvPPA (64%). Interpretation: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-β biomarkers in PPA patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Bergeron

Gorno‐Tempini

Rabinovici

et al. 2018

Annals of Neurology

Self Cite

149

111

View full text Add to dashboard Cite

show abstract

“…The Similarly, previous reports have demonstrated that patterns of atrophy in autosomal dominant forms are different than in sporadic FTD, with more widespread cortical involvement, including the parietal lobes. All of the bvFTD cases had genetic testing performed through research using previously described methods (Naasan et al, 2016).…”

Section: Change Maps In Amyloid-negative and Nongene Carrier Bvftd mentioning

confidence: 99%

Data‐driven regions of interest for longitudinal change in three variants of frontotemporal lobar degeneration

et al. 2017

Self Cite

View full text Add to dashboard Cite

IntroductionLongitudinal imaging of neurodegenerative disorders is a potentially powerful biomarker for use in clinical trials. In Alzheimer's disease, studies have demonstrated that empirically derived regions of interest (ROIs) can provide more reliable measurement of disease progression compared with anatomically defined ROIs.MethodsWe set out to derive ROIs with optimal effect size for quantifying longitudinal change in a hypothetical clinical trial by comparing atrophy rates in 44 patients with behavioral variant of frontotemporal dementia (bvFTD), 30 with the semantic variant primary progressive aphasia (svPPA), and 26 with the nonfluent variant PPA (nfvPPA) to atrophy in 97 cognitively healthy controls.ResultsThe regions identified for each variant were generally what would be expected from prior studies of frontotemporal lobar degeneration (FTLD). Sample size estimates for detecting a 40% reduction in annual rate of ROI atrophy varied substantially across groups, being 103 per arm in bvFTD, 31 in nfvPPA, and 10 in svPPA, but in all groups were less than those estimated for a priori ROIs and clinical measures. The variability in location of peak regions of atrophy across individuals was highest in bvFTD and lowest in svPPA, likely relating to the differences in effect size.ConclusionsThese findings suggest that, while cross‐validated maps of change can improve sensitivity to change in FTLD compared with a priori regions, the reliability of these maps differs considerably across syndromes. Future studies can utilize these maps to design clinical trials, and should try to identify factors accounting for the variability in patterns of atrophy across individuals, particularly those with bvFTD.

show abstract

O4‐01‐04: Amyloid in Dementia Associated With Familial Ftld: Not an Innocent Bystander

Cited by 2 publications

References 32 publications

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Data‐driven regions of interest for longitudinal change in three variants of frontotemporal lobar degeneration

Contact Info

Product

Resources

About