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

Teipel, Stefan J.; Heinsen, Helmut; Amaro, Edson; Grinberg, Lea T.; Krause, Bernd J.; Grothe, Michel J.

doi:10.1016/j.neurobiolaging.2013.09.029

Cited by 97 publications

(76 citation statements)

References 89 publications

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“…When hippocampal atrophy occurs independently of β-amyloid accumulation [21,22], it could reflect other underlying pathological processes including tauopathies, ischemia, and sclerosis [23]. Also, basal forebrain cholinergic system atrophy was more closely associated with cortical amyloid burden than was hippocampal atrophy in predementia AD [41]. …”

Section: Discussionmentioning

confidence: 99%

Relationship of Hippocampal Volume to Amyloid Burden across Diagnostic Stages of Alzheimer's Disease

Trzepacz

Hochstetler²,

Yu³

et al. 2015

Dement Geriatr Cogn Disord

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Aims: To assess how hippocampal volume (HV) from volumetric magnetic resonance imaging (vMRI) is related to the amyloid status at different stages of Alzheimer's disease (AD) and its relevance to patient care. Methods: We evaluated the ability of HV to predict the florbetapir positron emission tomography (PET) amyloid positive/negative status by group in healthy controls (HC, n = 170) and early/late mild cognitive impairment (EMCI, n = 252; LMCI, n = 136), and AD dementia (n = 75) subjects from the Alzheimer's Disease Neuroimaging Initiative Grand Opportunity (ADNI-GO) and ADNI2. Logistic regression analyses, including elastic net classification modeling with 10-fold cross-validation, were used with age and education as covariates. Results: HV predicted amyloid status only in LMCI using either logistic regression [area under the curve (AUC) = 0.71, p < 0.001] or elastic net classification modeling [positive predictive value (PPV) = 72.7%]. In EMCI, age (AUC = 0.70, p < 0.0001) and age and/or education (PPV = 63.1%), but not HV, predicted amyloid status. Conclusion: Using clinical neuroimaging, HV predicted amyloid status only in LMCI, suggesting that HV is not a biomarker surrogate for amyloid PET in clinical applications across the full diagnostic spectrum.

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Section: Discussionmentioning

confidence: 99%

Relationship of Hippocampal Volume to Amyloid Burden across Diagnostic Stages of Alzheimer's Disease

Trzepacz

Hochstetler²,

Yu³

et al. 2015

Dement Geriatr Cogn Disord

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“…Image analysis was done as described previously with SPM8 (Wellcome Trust Centre for Neuroimaging) using MR imaging for creating the object map (17). For 18 F-florbetapir and 11 C-Pittsburgh compound B, we used 1.36 and 1.4, respectively, as the thresholds for amyloid positivity for the mean cortical regions of interest normalized to cerebellar standardized uptake value ratio, based on the range of control in previous studies (18)(19)(20).…”

Section: Image Analysismentioning

confidence: 99%

Can Studies of Neuroinflammation in a TSPO Genetic Subgroup (HAB or MAB) Be Applied to the Entire AD Cohort?

et al. 2015

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Neuroinflammation plays a significant role in Alzheimer disease (AD), and translocator protein (TSPO) PET imaging allows us to quantify this process. However, the binding of second-generation TSPO tracers depends on the TSPO genotype coded by the rs6971 single-nucleotide polymorphism, with a 40%-50% increase in BP in high-affinity binders (HABs) compared with mixed-affinity binders (MABs), whereas low-affinity binders (LABs) are unsuitable for evaluation. Hence, several studies are using either HAB alone or HAB and MAB subjects. To translate the findings of neuroinflammation studies to the entire population, it is crucial to establish the influence of TSPO genotypes on AD. Here, we investigated whether different TSPO genotypes influence cognitive function, amyloid load, and disease progression over time. Methods: We evaluated 798 subjects (225 control, 388 with mild cognitive impairment [MCI], and 185 with AD) from the Alzheimer's Disease Neuroimaging Initiative database at baseline and during follow-up. All subjects were screened for TSPO genotype and underwent detailed clinical and neuropsychologic assessments yearly for 4 y. Of the 798 subjects, 255 also had T1-and T2-weighted MR imaging and amyloid PET with 11 C-Pittsburgh compound B or 18 F-florbetapir. Results: We demonstrated that all TSPO binding groups (HAB, MAB, and LAB) have same level of amyloid load in AD and MCI subjects. We also demonstrated that the prevalence is 50.3% for HAB, 41.2% for MAB, and 8.5% for LAB, without a statistical difference among the AD, MCI, and control groups. During longitudinal follow-up, the mean change in neuropsychometric test scores on the MiniMental State Examination, the cognitive and modified Alzheimer Disease Assessment Scales (ADASs), and the Geriatric Depression Scale over time were similar in AD and MCI subjects among the 3 TSPO binding groups. Analysis of the covariates showed that diagnostic group (control, MCI, AD), apolipoprotein E4 status, and sex had a significant effect on decline on the modified Alzheimer Disease Assessment Scale (.3 points of the scale), but age and TSPO genotype did not. Conclusion: This study suggests that information obtained from evaluating a subgroup of AD or MCI subject using second-generation TSPO tracers can be translated to the entire AD and MCI population. Thus, we can study fewer AD subjects in evaluating new antineuroinflammatory and antimicroglial agents in intervention studies and in observational studies evaluating the role of neuroinflammation.

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“…Higher Ab-amyloid burden as estimated with [ 18-F]Florbetapir correlates with decreased cerebral blood flow measured with ASL [95] and basal forebrain cholinergic system atrophy [96] in MCI and AD patients. However, Ab-amyloid deposition measured with [ 11 C]PIB has been shown to be independent of hippocampal neurodegeneration [97], suggesting that degeneration of the hippocampus and Ab-amyloid deposits could be at least partially different phenomena.…”

Section: Dementiamentioning

confidence: 98%

Recent imaging advances in neurology

2015

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Over the recent years, the application of neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) has considerably advanced the understanding of complex neurological disorders. PET is a powerful molecular imaging tool, which investigates the distribution and binding of radiochemicals attached to biologically relevant molecules; as such, this technique is able to give information on biochemistry and metabolism of the brain in health and disease. MRI uses high intensity magnetic fields and radiofrequency pulses to provide structural and functional information on tissues and organs in intact or diseased individuals, including the evaluation of white matter integrity, grey matter thickness and brain perfusion. The aim of this article is to review the most recent advances in neuroimaging research in common neurological disorders such as movement disorders, dementia, epilepsy, traumatic brain injury and multiple sclerosis, and to evaluate their contribution in the diagnosis and management of patients.

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

Cited by 97 publications

References 89 publications

Relationship of Hippocampal Volume to Amyloid Burden across Diagnostic Stages of Alzheimer's Disease

Relationship of Hippocampal Volume to Amyloid Burden across Diagnostic Stages of Alzheimer's Disease

Can Studies of Neuroinflammation in a TSPO Genetic Subgroup (HAB or MAB) Be Applied to the Entire AD Cohort?

Recent imaging advances in neurology

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