The Role of Biomarkers in Clinical Trials for Alzheimer Disease

Thal, Leon J.; Kantarci, Kejal; Reiman, Eric M.; Klunk, William E.; Weiner, Michael W.; Zetterberg, Henrik; Galasko, Douglas; Praticò, Domenico; Griffin, Sue T.; Schenk, Dale; Siemers, Eric

doi:10.1097/01.wad.0000191420.61260.a8

Cited by 205 publications

(161 citation statements)

References 95 publications

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“…In longitudinal studies, however, the heritability of biomarkers is expected to increase specificity and statistical power. We therefore propose that longitudinal mapping of the temporal structure of oscillations may prove valuable in preclinical trials aimed at investigating the progression and treatment response of patients with AD or other memory disorders (42).…”

Section: Discussionmentioning

confidence: 99%

“…2 A and B). The following filter settings were used (cut-off frequencies, filter order): delta (2-3 Hz, 251), theta (4 -5 Hz, 63), alpha (6 -13 Hz, 28), beta (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)28), and gamma (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)13). The mean oscillation amplitude was computed as the time-averaged amplitude envelope.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease

Montez

Poil

Jones

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

284

230

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Encoding and retention of information in memory are associated with a sustained increase in the amplitude of neuronal oscillations for up to several seconds. We reasoned that coordination of oscillatory activity over time might be important for memory and, therefore, that the amplitude modulation of oscillations may be abnormal in Alzheimer disease (AD). To test this hypothesis, we measured magnetoencephalography (MEG) during eyes-closed rest in 19 patients diagnosed with early-stage AD and 16 agematched control subjects and characterized the autocorrelation structure of ongoing oscillations using detrended fluctuation analysis and an analysis of the life-and waiting-time statistics of oscillation bursts. We found that Alzheimer's patients had a strongly reduced incidence of alpha-band oscillation bursts with long life-or waiting-times (< 1 s) over temporo-parietal regions and markedly weaker autocorrelations on long time scales (1-25 seconds). Interestingly, the life-and waiting-times of theta oscillations over medial prefrontal regions were greatly increased. Whereas both temporo-parietal alpha and medial prefrontal theta oscillations are associated with retrieval and retention of information, metabolic and structural deficits in early-stage AD are observed primarily in temporo-parietal areas, suggesting that the enhanced oscillations in medial prefrontal cortex reflect a compensatory mechanism. Together, our results suggest that amplitude modulation of neuronal oscillations is important for cognition and that indices of amplitude dynamics of oscillations may prove useful as neuroimaging biomarkers of early-stage AD.Alzheimer's disease ͉ magnetoencephalography ͉ neuronal oscillations ͉ resting-state brain activity ͉ temporal correlations P sychological and neuroimaging data suggest that the brain performs many important functions during rest, such as retrieval and manipulation of information in short-term memory, and problem-solving and planning (1, 2). These resting-state functions may represent an essential aspect of human selfawareness and are susceptible to impairment in brain-related disorders including depression, schizophrenia, and dementia (3).Neuroimaging has identified anatomical patterns of activity that are remarkably consistent across resting-state experiments, most notably in the precuneus, lateral parietal and medial prefrontal cortices (4, 5). The existence of such a ''resting-state network'' has been suggested to reflect a ''default mode'' of brain operation in the absence of goal-directed behavior (6). Coordination of anatomically distributed activity during rest has been studied extensively by computing correlations between neuronal signals from different brain areas (Fig. 1). This approach has revealed aberrant resting-state networks in Alzheimer disease (AD) (7-9) and other disorders (4, 10, 11).For cognitive processing, coordination of local brain activity over time may be just as important as the coordination of simultaneous activity in anatomically distinct brain regions and may be refl...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease

Montez

Poil

Jones

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

284

230

View full text Add to dashboard Cite

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“…Evaluation of the sensitivity and specificity of AD biomarkers involves comparison of biomarker measurements in AD cases and controls. Evaluation of potential AD biomarkers is thus hampered by the 10-15% diagnostic error rate in AD [32]. Studies incorporating postmortem confirmation of AD can avoid this problem, but for most studies this is not possible, hence this diagnostic inaccuracy should be considered when interpreting results.…”

Section: Another Promising Approach Is Pet Imaging Employing Ligandsmentioning

confidence: 99%

“…Compound-B (PIB), which selectively bind to Aβ plaques in vitro and in vivo, enabling plaque load to be imaged in living patients [31][32][33]. Interestingly, many MCI and a significant percentage (30%) of cognitively normal elderly individuals show high brain retention of PIB and low Aβ42 levels in the CSF [34][35].…”

Section: Another Promising Approach Is Pet Imaging Employing Ligandsmentioning

confidence: 99%

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

100

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Alzheimer's disease (AD) is the most common form of dementia and is characterized clinically by a progressive decline in memory, learning and executive function and neuropathologically by the presence of cerebral amyloid deposits. Despite a century of research, there is still no cure or conclusive pre-mortem diagnosis for the disease. A number of symptom-modifying drugs for AD have been developed, but their efficacy is minimal and short-lived. AD cognitive symptoms arise only after significant, irreversible neural deterioration has occurred, hence there is an urgent need to detect AD early, before the onset of cognitive symptoms. An accurate, early diagnostic test for AD would enable current and future treatments to be more effective, as well as contribute to the development of new treatments.While most AD related pathology occurs in the brain, the disease has also been reported to affect the eye, which is more accessible for imaging than the brain. AD-related proteins exist in the normal human eye and may produce ocular pathology in AD. There is some homology between the retinal and cerebral vasculatures and the retina also contains nerve cells and fibers that form a sensory extension of the brain. The eye is the only place in the body where vasculature or neural tissue is available for non-invasive optical imaging. This article presents a review of current literature on ocular morphology in AD and discusses the potential for an ocular based screening test for AD.

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“…Otras sustancias relevantes en LCR son los isoprostanos F2 (IPF2), elevados en pacientes con EA, correlacionando con t-tau y Aβ 42 42 . Pacientes con DCL con alta concentración de IPF2A 43,44 . También se han explorado proteínas sinápticas (e.g.…”

Section: Biomarcadoresunclassified

Evaluación de la enfermedad de Alzheimer en etapa temprana: biomarcadores y pruebas neuropsicológicas

Lanfranco

Manríquez-Navarro

et al. 2012

Rev. méd. Chile

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The Role of Biomarkers in Clinical Trials for Alzheimer Disease

Cited by 205 publications

References 95 publications

Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease

Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Evaluación de la enfermedad de Alzheimer en etapa temprana: biomarcadores y pruebas neuropsicológicas

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