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.


Available from: Harald J Hampel
    • "This neuropathology, further developing throughout the mild-to-moderate stage, disrupts important networks connecting the medial temporal lobe and the frontal lobe (Bastos Leite et al., 2004; Scherder, Eggermont, Visscher, Scheltens, & Swaab, 2011), and additional cortical thinning of the temporal and posterior parietal lobes is seen (Ewers et al., 2011). In the most advanced stage, according to both post-mortem research (Braak & Braak, 1991; Swaab, Dubelaar, Scherder, van Someren, & Verwer, 2003) and neuroimaging studies (Ewers et al., 2011), the primary somatosensory cortex shows least AD-related degeneration. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Little is known about the experience of people with dementia while playing games. This might be a reason why hardly any games are specifically designed for this group. We aimed to determine which play experiences can be expected to be suitable for persons in different stages of Alzheimer’s disease (AD). Twenty-two play experiences were related to the neuropathology that is characteristic of the different stages of dementia: earliest, mild-to-moderate, and severe. This literature overview is based on neuroimaging, neuropathological, and clinical studies. We found that for all older persons with AD, regardless of disease severity, the play experiences sensation, relaxation, and reminiscence are likely to be suitable. The play experiences nurture, sympathy, fellowship, expression, humour, eroticism, subversion, and challenge may be appropriate only for those in the earliest and mild-to-moderate stages of AD. The play experience exploration is most likely not suitable, irrespective of the stage of AD. For the remaining play experiences we did not find sufficient evidence to draw conclusions. We conclude that the choice of play experiences in game design for older persons with AD is dependent on disease stage. Current recommendations may contribute to tailor-made games that are suitable for different persons with AD.
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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
Show more