Download Early detection of Alzheimer`s disease using

This is a selection of sound scientific reviews on applications of brain imaging technologies that the
bid team considers particularly new and relevant to society. From the study of consciousness
disorders to the diagnosis of Alzheimer’s disease find out what interests you the most
Nature. 2008 Jun 12;453(7197):869-78.
What we can do and what we cannot do with fMRI
Logothetis NK.
Functional magnetic resonance imaging (fMRI) is currently the mainstay of neuroimaging in
cognitive neuroscience. Advances in scanner technology, image acquisition protocols, experimental
design, and analysis methods promise to push forward fMRI from mere cartography to the true
study of brain organization. However, fundamental questions concerning the interpretation of fMRI
data abound, as the conclusions drawn often ignore the actual limitations of the methodology. Here
I give an overview of the current state of fMRI, and draw on neuroimaging and physiological data
to present the current understanding of the haemodynamic signals and the constraints they impose
on neuroimaging data interpretation.
Mol Imaging Biol. 2004 Jul-Aug;6(4):239-69.
Positron emission tomography in clinical neurology
Herholz K, Heiss WD.
Positron emission tomography (PET) imaging in clinical neurology serves several purposes:
differential diagnosis, especially in the early stage of neurologic disorders, description of
pathophysiologic changes that are responsible for manifestation and course of a disease, and
evaluation and follow-up of treatment effects. Many of these applications are possible with the most
widely available PET tracer, 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Additional tracers are used
clinically to detect the disturbance of specific neurotransmitter and receptor systems, blood flow,
oxygen metabolism, and amino acid uptake. Main diagnostic issues addressed in this review are
early diagnosis of Alzheimer's disease and other dementias, differential diagnosis of movement
disorders, diagnosis of recurrent brain tumors, identification of viable tissue in ischemic stroke, and
localization of epileptogenic foci. Techniques for presurgical localization of eloquent cortex and
monitoring of therapy are presented.
Curr Opin Neurol. 2007 Dec;20(6):632-7.
Functional MRI in disorders of consciousness: advantages and limitations.
Owen AM, Coleman MR.
PURPOSE OF REVIEW: We discuss recent developments in the use of neuroimaging and, in
particular, functional MRI, in the assessment of patients diagnosed as vegetative state or minimally
conscious state. RECENT FINDINGS: In the last year, there has been a substantial increase in the
number of research studies published which have used state-of-the-art neuroimaging methods to
assess residual cognitive functioning in patients diagnosed with disorders of consciousness. Work
using functional MRI has demonstrated aspects of retained speech processing, emotional
processing, comprehension and even conscious awareness in a small number of patients
behaviourally meeting the criteria defining the vegetative and minimally conscious states.
SUMMARY: The assessment of patients with disorders of consciousness relies heavily upon the
subjective and consequently fallible interpretation of observed behaviour. Recent studies have
demonstrated an important role for functional MRI in the identification of residual cognitive
function in these patients. Such studies may be particularly useful when there is concern about the
accuracy of the diagnosis and the possibility that residual cognitive function has remained
undetected. In our opinion, the future use of functional MRI will substantially increase our
understanding of disorders of consciousness following severe brain injury.
J Cogn Neurosci. 2000 Jan;12(1):1-47.
Imaging cognition II: An empirical review of 275 PET and fMRI studies.
Cabeza R, Nyberg L.
Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have been
extensively used to explore the functional neuroanatomy of cognitive functions. Here we review
275 PET and fMRI studies of attention (sustained, selective, Stroop, orientation, divided),
perception (object, face, space/motion, smell), imagery (object, space/motion), language
(written/spoken word recognition, spoken/no spoken response), working memory (verbal/numeric,
object, spatial, problem solving), semantic memory retrieval (categorization, generation), episodic
memory encoding (verbal, object, spatial), episodic memory retrieval (verbal, nonverbal, success,
effort, mode, context), priming (perceptual, conceptual), and procedural memory (conditioning,
motor, and nonmotor skill learning). To identify consistent activation patterns associated with these
cognitive operations, data from 412 contrasts were summarized at the level of cortical Brodmann's
areas, insula, thalamus, medial-temporal lobe (including hippocampus), basal ganglia, and
cerebellum. For perception and imagery, activation patterns included primary and secondary
regions in the dorsal and ventral pathways. For attention and working memory, activations were
usually found in prefrontal and parietal regions. For language and semantic memory retrieval,
typical regions included left prefrontal and temporal regions. For episodic memory encoding,
consistently activated regions included left prefrontal and medial temporal regions. For episodic
memory retrieval, activation patterns included prefrontal, medial temporal, and posterior midline
regions. For priming, deactivations in prefrontal (conceptual) or extrastriate (perceptual) regions
were consistently seen. For procedural memory, activations were found in motor as well as in nonmotor brain areas. Analysis of regional activations across cognitive domains suggested that several
brain regions, including the cerebellum, are engaged by a variety of cognitive challenges. These
observations are discussed in relation to functional specialization as well as functional integration.
2006 Aug;79(1):77-115.
New concepts in surgery of WHO grade II gliomas: functional brain mapping, connectionism
and plasticity-a review.
Duffau H.
Despite a recent literature supporting the impact of surgery on the natural history of low-grade
glioma (LGG), the indications of resection still remain a matter of debate, especially because of the
frequent location of these tumors within eloquent brain areas - thus with a risk to induce a
permanent postoperative deficit. Therefore, since the antagonist nature of this surgery is to perform
the most extensive glioma removal possible, while preserving the function and the quality of life,
new concepts were recently applied to LGG resection in order to optimize the benefit/risk ratio of
the surgery.First, due to the development of functional mapping methods, namely perioperative
neurofunctional imaging and intrasurgical direct electrical stimulation, the study of cortical
functional organization is currently possible for each patient - in addition to an extensive
neuropsychological assessment. Such knowledge is essential because of the inter-individual
anatomo-functional variability, increased in tumors due to cerebral plasticity phenomena. Thus,
brain mapping enables to envision and perform a resection according to individual functional
boundaries.Second, since LGG invades not only cortical but also subcortical structures, and shows
an infiltrative progression along the white matter tracts, new techniques of anatomical tracking and
functional mapping of the subcortical white matter pathways were also used with the goal to study
the individual effective connectivity - which needs imperatively to be preserved during the
resection.Third, the better understanding of brain plasticity mechanisms, induced both by the slowgrowing LGG and by the surgery itself, were equally studied in each patient and applied to the
surgical strategy by incorporating individual dynamic potential of reorganization into the operative
planning.The integration of these new concepts of individual functional mapping, connectivity and
plastic potential to the surgery of LGG has allowed an extent of surgical indications, an
optimization of the quality of resection (neuro-oncological benefit), and a minimization of the risk
of sequelae (benefit on the quality of life). In addition, such a strategy has also fundamental
applications, since it represents a new door to the connectionism and cerebral plasticity.
Exp Gerontol. 2007 Jan-Feb;42(1-2):129-38.
Early detection of Alzheimer's disease using neuroimaging.
Mosconi L, Brys M, Glodzik-Sobanska L, De Santi S, Rusinek H, de Leon MJ.
Neuroimaging is being increasingly used to complement clinical assessments in the early detection
of Alzheimer's disease (AD). Structural magnetic resonance imaging (MRI) and metabolic positron
emission tomography (FDG-PET) are the most clinically used and promising modalities to detect
brain abnormalities in individuals who might be at risk for AD but who have not yet developed
symptoms. The knowledge of established risk factors for AD enabled investigators to develop
enrichment strategies for longitudinal imaging studies to reduce the sample sizes and study
duration. The present review focuses on the results obtained by MRI and FDG-PET studies that
examined the preclinical AD stages in several at risk populations: (1) individuals from families with
autosomal dominant early-onset AD (FAD), (2) patients with mild cognitive impairment (MCI),
particularly in memory, who are at very high risk for declining to AD with an estimated decline rate
of 10-30% per year, (3) normal young and middle-age subjects carriers of known susceptibility
genes for late-onset AD such as the Apolipoprotein E (ApoE) E4 allele, and (4) as age is the main
risk factor for AD, normal elderly individuals followed to the onset of MCI and AD. Overall, these
studies show that the use of imaging for the early detection of AD is successful even in the earlier
stages of disease when clinical symptoms are not fully expressed and the regional brain damage
may be limited.
Neurology. 2008 Apr 15;70(16 Pt 2):1478-88.
Functional imaging in Parkinson disease.
Nandhagopal R, McKeown MJ, Stoessl AJ.
OBJECTIVE: Functional imaging techniques represent useful tools to assess in vivo the
neurochemical alterations and functional connectivity in Parkinson disease (PD). Here, the authors
review the various approaches and potential application of these imaging techniques to the study of
PD. METHOD: Radiotracer imaging using dopaminergic markers facilitates assessment of pre- and
postsynaptic nigrostriatal integrity, while imaging with other appropriate radiotracers explores
nondopaminergic neurotransmitter function, local metabolism, blood flow, and mechanisms
potentially related to disease progression and pathogenesis. Activation studies using functional MRI
detect blood oxygen level dependent signal, as an indirect marker of neuronal activity. RESULT:
Functional imaging techniques have been applied to infer the potential role of inflammation and
other factors in etiopathogenesis as well as to study compensatory and regulatory mechanisms in
early PD and subclinical disease in genetic forms of PD. Imaging studies also help to understand the
neurobiological basis of motor and nonmotor complications. Recent reports suggest a role for
striatal dopaminergic transmission in modulating neurobehavioral processes including the placebo
effect in PD. Although functional imaging has been employed to monitor disease progression, the
discordance between clinical outcome and imaging measures after therapeutic interventions
precludes their use as surrogate end points in clinical trials. Beyond these limitations and potential
challenges, imaging techniques continue to find wide application in the study of PD.
CONCLUSION: Functional imaging can provide meaningful insights into mechanisms underlying
various aspects of motor and nonmotor dysfunction in Parkinson disease and the role of striatal
dopaminergic transmission in behavioral processes beyond motor control. These modalities hold
promise to study the preclinical phase and to elucidate further the benefits and complications of
surgical interventions and the utility of neuroprotective strategies.
J Magn Reson Imaging. 2006 Jun;23(6):851-61.
Applications of functional magnetic resonance imaging in psychiatry.
Mitterschiffthaler MT, Ettinger U, Mehta MA, Mataix-Cols D, Williams SC.
While the use of MRI techniques has become a cornerstone of the neurology clinic, the application
of such methods in psychiatry was rather limited until the advent of functional magnetic resonance
imaging (fMRI). Over the past decade fMRI has superseded radionuclide-imaging techniques and
blossomed into a widely used psychiatric research tool. This review focuses on the neurobiological
findings from fMRI research in three less well-documented psychiatric disorders: attention deficit
hyperactivity disorder (ADHD), depression, and obsessive-compulsive disorder (OCD). Although
there was some disparity in early findings, greater standardization of image acquisition, analysis,
and paradigms, and improved clinical classification are leading to a greater convergence of
observations from different laboratories. fMRI is also beginning to realize its potential as an
important mediator between genes and phenotypes, and may thus contribute to a better
understanding of the pathophysiology of major neuropsychiatric diseases. The role of fMRI in the
objective assessment of therapeutic intervention and early prediction of response to treatment is also
discussed. Copyright 2006 Wiley-Liss, Inc.
Trends Pharmacol Sci. 2008 Feb;29(2):91-8.
Functional neuroimaging in schizophrenia: diagnosis and drug discovery.
McGuire P, Howes OD, Stone J, Fusar-Poli P.
Functional neuroimaging provides a direct way of investigating the pathophysiology of
schizophrenia in vivo. The function of neurotransmitters implicated in schizophrenia, such as
dopamine and glutamate, can be assessed using molecular imaging techniques such as positron
emission tomography (PET), single-photon emission tomography (SPET) and magnetic resonance
spectroscopy (MRS). Regional brain activity, particularly that associated with the cognitive
processes and symptoms associated with the disorder, can be studied using functional magnetic
resonance imaging (fMRI). Here, we focus on the potential for the use of these techniques in the
diagnosis of schizophrenia and in the development of new drugs for its treatment.