Staging Alzheimer's disease progression with multimodality neuroimaging

Department of Radiology, University of California at San Francisco, San Francisco, USA.
Progress in Neurobiology (Impact Factor: 9.99). 06/2011; 95(4):535-46. DOI: 10.1016/j.pneurobio.2011.06.004
Source: PubMed


Rapid developments in medical neuroimaging have made it possible to reconstruct the trajectory of Alzheimer's disease (AD) as it spreads through the living brain. The current review focuses on the progressive signature of brain changes throughout the different stages of AD. We integrate recent findings on changes in cortical gray matter volume, white matter fiber tracts, neuropathological alterations, and brain metabolism assessed with molecular positron emission tomography (PET). Neurofibrillary tangles accumulate first in transentorhinal and cholinergic brain areas, and 4-D maps of cortical volume changes show early progressive temporo-parietal cortical thinning. Findings from diffusion tensor imaging (DTI) for assessment fiber tract integrity show cortical disconnection in corresponding brain networks. Importantly, the developmental trajectory of brain changes is not uniform and may be modulated by several factors such as onset of disease mechanisms, risk-associated and protective genes, converging comorbidity, and individual brain reserve. There is a general agreement between in vivo brain maps of cortical atrophy and amyloid pathology assessed through PET, reminiscent of post mortem histopathology studies that paved the way in the staging of AD. The association between in vivo and post mortem findings will clarify the temporal dynamics of pathophysiological alterations in the development of preclinical AD. This will be important in designing effective treatments that target specific underlying disease AD mechanisms.

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    • "Regardless of DTI sensitivity in assessing WM microstructural changes, differences in diffusion patterns across clinical groups may be challenging to interpret [1]. Several studies reported DTI changes in the parahippocampus, hippocampus , posterior cingulum, and splenium even at the MCI stage [9] [10] [11] [12] [13]. Widespread areas of DTI abnormalities may also be observed in AD. "
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    ABSTRACT: Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD) and may reflect primary or secondary circuitry degeneration (i.e., due to cortical atrophy). The interpretation of diffusion tensor imaging (DTI) eigenvectors, known as multiple indices, may provide new insights into the main pathological models supporting primary or secondary patterns of WM disruption in AD, the retrogenesis, and Wallerian degeneration models, respectively. The aim of this review is to analyze the current literature on the contribution of DTI multiple indices to the understanding of AD neuropathology, taking the retrogenesis model as a reference for discussion. A systematic review using MEDLINE, EMBASE, and PUBMED was performed. Evidence suggests that AD evolves through distinct patterns of WM disruption, in which retrogenesis or, alternatively, the Wallerian degeneration may prevail. Distinct patterns of WM atrophy may be influenced by complex interactions which comprise disease status and progression, fiber localization, concurrent risk factors (i.e., vascular disease, gender), and cognitive reserve. The use of DTI multiple indices in addition to other standard multimodal methods in dementia research may help to determine the contribution of retrogenesis hypothesis to the understanding of neuropathological hallmarks that lead to AD.
    BioMed Research International 11/2014; 2015. DOI:10.1155/2015/291658 · 2.71 Impact Factor
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    • "Neuroimaging research in the field of dementia focuses on the impact of behavioral, neuropsychological, genetic and demographic factors on brain atrophy associated with transition from healthy aging through mild cognitive impairment (MCI) and further to Alzheimer's disease (AD) (Buckner, 2004; Ewers et al., 2011; Fonteijn et al., 2012; Förster et al., 2012; Gao et al., 1998; Gomar et al., 2011; Good et al., 2001; Jedynak et al., 2012; Johnson et al., 2009; Tisserand et al., 2004). "
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    ABSTRACT: The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage.
    Clinical neuroimaging 07/2013; 3:84–94. DOI:10.1016/j.nicl.2013.07.005 · 2.53 Impact Factor
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    • "Indeed our patient's phenotype overlapped on clinical and neuroimaging grounds with lv-PPA, although did not fulfill current criteria for lv-PPA (owing to the presence of impaired motor speech production and expressive agrammatism [1]). The frequently observed overlap of neurodegenerative syndromes might plausibly reflect disease propagation through distributed functional networks [22] [23]. The mechanisms by which brain networks are rendered vulnerable and subsequently degenerate remain to be elucidated. "
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    ABSTRACT: Primary progressive aphasia (PPA) represents a diverse group of language-led dementias most often due to frontotemporal lobar degeneration. We report clinical, neuropsychological, and neuroimaging data in the case of a 47-year-old woman presenting with non-fluent PPA due to a genetically confirmed pathogenic Presenilin 1 P264L mutation. This case highlights an unusual clinical presentation of familial Alzheimer's disease and a novel presentation of the P264L mutation. The case adds to accumulating evidence that particular mutations can promote specific brain network degeneration, with wider implications for understanding the sporadic forms of Alzheimer's disease and PPA.
    Journal of Alzheimer's disease: JAD 04/2013; 36(2). DOI:10.3233/JAD-122092 · 4.15 Impact Factor
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