Modeling regional vulnerability to Alzheimer pathology

Abstract

Latent growth curve (LGC) models estimate change over time in a cohort's serially obtained measurements. We have applied LGC techniques to a spatial distribution of Alzheimer's disease (AD) pathology using autopsy data from 435 participants in the Honolulu-Asia Aging Study. Neurofibrillary tangle (NFT) and neuritic plaques (NP) were distributed across differently ordered sets of anatomical regions. The gradient of spatial change in NP (dNP), was significantly associated with that of NFT (dNFT), but weakly and inversely (r = -0.12, p <0.001). Both dNFT and dNP correlated significantly and inversely with Braak stage. 61% of the variance in Braak stage was explained by dNFT independent of covariates. Only dNFT was significantly associated with longitudinal change in cognition. Only dNP was associated with apolipoprotein (APOE) e4 burden. This is the first application of LGC models to spatially ordered data. The result is a quantification of the inter-individual variation in the inter-regional vulnerability to AD lesions.

The Temporospatial Evolution of Neuritic Plaque-Related and Independent Tauopathies: Implications for Dementia Staging

“…We have previously shown in HAAS data that NP are arranged corticofugally in space [2] and that neocortical NFT develop contemporaneously with neocortical NP over the course of CASI surveillance [11]. This supports our conclusion that NP-related NFT formation is corticofugal, and suggests that the process has clinical consequences.…”

“…Mean lesion counts by anatomical region have been reported elsewhere [2]. Model fit was excellent (χ 2 :df = 108.0:32, p <0.001; RMSEA = 0.027; CFI= 0.976; BCC = 315.05).…”

“…NFT in hippocampal regions (CA1 |r| = 0.58; subiculum In general, these factor loadings reveal that regional NP-related NFT counts share most variance with NP counts in the same structures. This does not seem surprising until one realizes that the observable corticofugal temporal spread of amyloid-␤ is incompatible with the hypothesized corticotropic temporal spread of NFT hypothesized by Braak, and confirmed in crosssectional autopsy data [2].…”

The Temporospatial Evolution of Neuritic Plaque-Related and Independent Tauopathies: Implications for Dementia Staging

“…We have previously shown in HAAS data that NP are arranged corticofugally in space [2] and that neocortical NFT develop contemporaneously with neocortical NP over the course of CASI surveillance [11]. This supports our conclusion that NP-related NFT formation is corticofugal, and suggests that the process has clinical consequences.…”

“…Mean lesion counts by anatomical region have been reported elsewhere [2]. Model fit was excellent (χ 2 :df = 108.0:32, p <0.001; RMSEA = 0.027; CFI= 0.976; BCC = 315.05).…”

“…NFT in hippocampal regions (CA1 |r| = 0.58; subiculum In general, these factor loadings reveal that regional NP-related NFT counts share most variance with NP counts in the same structures. This does not seem surprising until one realizes that the observable corticofugal temporal spread of amyloid-␤ is incompatible with the hypothesized corticotropic temporal spread of NFT hypothesized by Braak, and confirmed in crosssectional autopsy data [2].…”

Cholinergic basal forebrain atrophy predicts amyloid burden in Alzheimer's disease

“…In mild cognitive impairment (MCI) stages of AD, hippocampus atrophy has not been associated with global or regional amyloid accumulation in most studies (Apostolova et al, 2010; Chetelat et al, 2010b). Thus, associations between cortical amyloid deposition and hippocampus atrophy were relatively weak, consistent with postmortem evidence that amyloid pathology occurs in the hippocampus only secondary to neurofibrillary pathology (Braak and Braak, 1997; Royall et al, 2012). …”

Estimating the Temporal Evolution of Alzheimer's Disease Pathology with Autopsy Data

“…1 and 2. Mean lesion counts by anatomical region have been reported elsewhere [25]. Mean CASI scores fell linearly by -1.75 points/year (Fig.…”

The Temporospatial Evolution of Neuritic Plaque-Related and Independent Tauopathies: Implications for Dementia Staging

“…We have previously shown in HAAS data that NP are arranged corticofugally in space [2] and that neocortical NFT develop contemporaneously with neocortical NP over the course of CASI surveillance [11]. This supports our conclusion that NP-related NFT formation is corticofugal, and suggests that the process has clinical consequences.…”

“…Mean lesion counts by anatomical region have been reported elsewhere [2]. Model fit was excellent (χ 2 :df = 108.0:32, p <0.001; RMSEA = 0.027; CFI= 0.976; BCC = 315.05).…”

“…NFT in hippocampal regions (CA1 |r| = 0.58; subiculum In general, these factor loadings reveal that regional NP-related NFT counts share most variance with NP counts in the same structures. This does not seem surprising until one realizes that the observable corticofugal temporal spread of amyloid-␤ is incompatible with the hypothesized corticotropic temporal spread of NFT hypothesized by Braak, and confirmed in crosssectional autopsy data [2].…”

Cholinergic basal forebrain atrophy predicts amyloid burden in Alzheimer's disease

“…In mild cognitive impairment (MCI) stages of AD, hippocampus atrophy has not been associated with global or regional amyloid accumulation in most studies (Apostolova et al, 2010; Chetelat et al, 2010b). Thus, associations between cortical amyloid deposition and hippocampus atrophy were relatively weak, consistent with postmortem evidence that amyloid pathology occurs in the hippocampus only secondary to neurofibrillary pathology (Braak and Braak, 1997; Royall et al, 2012). …”

Estimating the Temporal Evolution of Alzheimer's Disease Pathology with Autopsy Data

“…1 and 2. Mean lesion counts by anatomical region have been reported elsewhere [25]. Mean CASI scores fell linearly by -1.75 points/year (Fig.…”

The Temporospatial Evolution of Neuritic Plaque-Related and Independent Tauopathies: Implications for Dementia Staging

“…We have previously shown in HAAS data that NP are arranged corticofugally in space [2] and that neocortical NFT develop contemporaneously with neocortical NP over the course of CASI surveillance [11]. This supports our conclusion that NP-related NFT formation is corticofugal, and suggests that the process has clinical consequences.…”

“…Mean lesion counts by anatomical region have been reported elsewhere [2]. Model fit was excellent (χ 2 :df = 108.0:32, p <0.001; RMSEA = 0.027; CFI= 0.976; BCC = 315.05).…”

“…NFT in hippocampal regions (CA1 |r| = 0.58; subiculum In general, these factor loadings reveal that regional NP-related NFT counts share most variance with NP counts in the same structures. This does not seem surprising until one realizes that the observable corticofugal temporal spread of amyloid-␤ is incompatible with the hypothesized corticotropic temporal spread of NFT hypothesized by Braak, and confirmed in crosssectional autopsy data [2].…”

Cholinergic basal forebrain atrophy predicts amyloid burden in Alzheimer's disease

“…In mild cognitive impairment (MCI) stages of AD, hippocampus atrophy has not been associated with global or regional amyloid accumulation in most studies (Apostolova et al, 2010; Chetelat et al, 2010b). Thus, associations between cortical amyloid deposition and hippocampus atrophy were relatively weak, consistent with postmortem evidence that amyloid pathology occurs in the hippocampus only secondary to neurofibrillary pathology (Braak and Braak, 1997; Royall et al, 2012). …”

Estimating the Temporal Evolution of Alzheimer's Disease Pathology with Autopsy Data

“…1 and 2. Mean lesion counts by anatomical region have been reported elsewhere [25]. Mean CASI scores fell linearly by -1.75 points/year (Fig.…”