Escolar Documentos
Profissional Documentos
Cultura Documentos
0001-2998/12/$-see front matter & 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1053/j.semnuclmed.2013.06.003
450
Quantication Strategies
One of the strengths of PET brain imaging lies in the ability
to accurately quantify radiotracer distribution in brain.
Epilepsy
Background and Potential Effect
Epilepsy, the predisposition to recurrent, unprovoked
seizures,30 is estimated to affect approximately 1% of the
population and 3% at some point in their lives.30-32 Approximately 30% of these patients have intractable epilepsy because
pharmacologic therapy is insufcient to reduce seizure frequency.32,33 Clinical interventions for drug-resistant epilepsy,
including intracranial stimulation, vagal nerve stimulation, and
surgical resection of brain, have been proven to have various
degrees of efcacy at achieving seizure relief.34,35 Surgical brain
resection, in the appropriate clinical context, is the most widely
accepted treatment for intractable epilepsy. However, epilepsy
is not a homogeneous condition, rather it consists of a
spectrum of syndromes, etiologies, and seizure types.36,37
Figure 1 Normal uorodeoxyglucose (18-F) brain uptake seen in the transaxial (A), sagittal (B), and coronal (C) planes.
Note the most intense uptake is present in the striatum followed closely by the thalami and occipital cortex (transaxial
view). FDG distribution is evenly distributed throughout the remaining cortices, slightly decreased in the temporal lobes
(coronal and sagittal views).
451
ictal (F-18) FDG-PET imaging remains impractical in the
clinical setting.
Outcomes
The goal for surgical resection is complete seizure freedom.
Engel developed a classication scale for postoperative outcomes: class I (free of disabling seizures), class II (rare disabling
seizures), class III (worthwhile improvement), and class IV (not
worthwhile improvement).32,51 This ordinal scale is often used
for determining postoperative seizure control.52 The other
prominent postoperative classication is the 6-point scale
developed by the International League Against Epilepsy.53 In
classic mesial temporal lobe epilepsy, ndings of hippocampal
atrophy and ipsilateral temporal lobe hypometabolism are
present. A representative case of mesial temporal sclerosis
associated with epilepsy is shown in Figure 2. However, there
is building evidence that even in the absence of a morphologic
lesion seen on MRI, patients with temporal lobe hypometabolism that is concordant with EEG abnormalities or seizure
semiology or both may have signicant freedom from seizures
after temporal lobe resection.54-57 However, there remains
signicant information to be gained using MRI.58,59 As a
spatially rigid structure, the brain lends itself well to coregistration between imaging modalities. Specically, several studies
have examined the potential of MRI and (F-18) FDG-PET
coregistration.57,60,61 The two57,61 techniques found signicant benet of coregistration for detection of hypometabolic
foci in patients with focal cortical dysplasias, a signicant cause
of epilepsy in which neurons fail to migrate appropriately
during brain development.62
452
Figure 2 Representative transaxial FDG-PET and MRI FLAIR images from a 20-year-old female with intractable seizures. On
MRI, note the shrunken-appearing left hippocampus (B). The FDG-PET demonstrates hypometabolism throughout the left
temporal lobe (A).
to seizure onsent using the radioligand (F-18)-(N-[2-{4-(2methoxyphenyl) piperazino}]-N-[2-pyridinyl]trans-4-uorocyclohexanecarboxamide) (FCWAY) has been demonstrated
in several studies.89-91,98-100 This asymmetry has been
observed to be more prominent than hypometabolism seen
with (F-18) FDG-PET,90 and, in turn, it has been suggested
that PET serotonin receptor mapping may have signicant
benet for surgical planning91 for patients with intractable
temporal lobe epilepsy. Because tryptophan, an essential
amino acid, is critical for serotonin synthesis, (C-11)-labeled
tryptophan has been used as a surrogate marker to study
epilepsy.101-108 Interestingly, increased tryptophan metabolism was observed in temporal cortex ipsilateral to seizure
onset,108 and tryptophan metabolism increased in the lentiform nucleus ipsilateral to side of seizure onset after temporal
lobe resection.102 Focal increases in amino acid metabolism
have been postulated to occur in epileptogenic neocortical
lesions such as focal cortical dysplasias and tuberous sclerosis;
there is evidence that (C-11) tryptophan PET imaging can
identify these lesions better than MRI or (F-18) FDG-PET
imaging.101,103-105,107 (C-11)-labeled methionine, another
essential amino acid, has also been shown to be focally
increased in focal cortical dysplasia.109,110
Intractable epilepsy represents a challenging disease to treat
as the underlying neuronal changes that result in successful
outcomes remain uncertain.67,111,112 Despite treatment improvements, some patients do not achieve seizure relief.35,40
Improved understanding of changes occurring during both
successful and unsuccessful therapy would enhance clinical
decision making and improve understanding of adult neuronal
reorganization as well as potentially suggest novel treatment
strategies. PET brain imaging, using traditional (18-F) FDG as
well as novel radiopharmaceuticals, is well poised to drive this
process.
Dementia
Dementia is dened as a decline of cognitive or neuropsychological function not explained by other psychiatric disorder
that interferes with usual activities. Cognitive and behavioral
Alzheimer Dementia
AD is a progressive neurodegenerative disease with an insidious cognitive decline that is characterized by a combination of
inability to acquire new memories, impaired reasoning and
judgment, impaired visuospatial ability, impaired language
function, and changes in personality and behavior.121 AD
accounts for approximately 50%-60% of all causes of dementia. The incidence of AD increases with age.122 AD is
pathologically associated with accumulation of amyloid neuritic plaques and neurobrillary tangles containing the tau
protein.123 Recent estimates of the prevalence of AD in the
United States range from 2.4-4.5 million people124; numbers
projected to continue to increase as the population continues
to get older.
It has been recognized that the pathophysiological processes
that underlie AD commence years before patients can be
classied as demented; there is evidence that amyloid accumulation precedes the onset of clinical symptoms by many
years.125 Memory complaints, other milder cognitive decits,
and abnormalities on neurocognitive testing can be detected in
a group of nondemented patients who belong to this predementia phase of Alzheimer disease termed mild cognitive
impairment (MCI), years before the onset of dementia.126,127
The prevalence of MCI in the United States is approximately
5.2 million people.128 Patients with MCI have a greater rate of
cognitive decline129 and greater risk of progression to dementia
than patients with normal cognition,130 with conversion to AD
estimated between 5%-16% per year,131 but up to one-third
453
revert to normal cognition.132 Furthermore, efforts have been
made to identify cognitively normal patients with the earliest
pathophysiological changes characteristic of AD.133
On FDG-PET, AD demonstrates a characteristic temporal
and parietal hypometabolism with involvement of the medial
parietal lobe including the precuneus and the posterior
cingulate cortex (Fig. 3A). Temporoparietal hypometabolism
is the characteristic nding134 and is seen early in the disease
course, with more advanced cases also showing worsening
hypometabolism more broadly in the brain, particularly in the
frontal lobes.135 There is typically sparing of primary somatosensory cortex, visual cortex, the basal ganglia and thalami, and
the cerebellum. This pattern of hypometabolism may be
asymmetric but is usually bilateral.136,137
Numerous studies, both small and large, have evaluated the
performance of FDG-PET for the diagnosis of AD. Sensitivity
and specicity values have varied, but reasonable estimates
for the sensitivity is 78%-94% and for specicity is
63%-86%.113,114,134,138-140 Studies have shown that FDGPET provides useful information in the evaluation of a
demented patient. A study by LaForce et al.141 demonstrated
that in a cohort of patients with MCI and AD, the diagnoses of
29% of cases were changed based on FDG-PET, with FDGPET being most useful in atypical or uncertain etiologies of
dementia. FDG-PET has been shown to have modestly greater
sensitivity and specicity than initial clinical examination.139,141 Patients with amnestic MCI and patients
with MCI with multiple cognitive domains affected tend to
demonstrate an AD pattern, with the severity of hypometabolism less severe than in AD. MCI remains a heterogeneous
population owing to the difculty in establishing the
underlying pathophysiology, and many MCI cases demonstrate normal or other patterns of hypometabolism on FDGPET.135
FDG-PET studies can be used to derive prognostic information for patients with AD and MCI. Lower metabolism at
baseline was associated with poorer cognitive performance142
and subsequent cognitive and functional decline.137 Worsening of hypometabolism in AD and in MCI is associated with
progressive cognitive and functional decline.136,137,143 Furthermore, an AD pattern of hypometabolism in patients with
MCI is correlated with progression to AD.136,140 On the
contrary, a normal appearance on FDG-PET is strong evidence
that MCI is not due to an underlying neurodegenerative
condition.135
454
Figure 3 Typical FDG uptake patterns in neurodegenerative dementias. (A) Alzheimer dementia characteristically features
parietotemporal hypometabolism. (B) Dementia with Lewy bodies also demonstrates parietotemporal hypometabolism;
however, additional occipital hypometabolism is often present, a nding not characteristic for AD. (C) Frontal variant
frontotemporal dementia with classical frontal and temporal hypometabolism. (D) Progressive nonuent aphasia variant of
FTD with marked asymmetry, almost exclusively involving the left temporal and parietal lobes.
455
with approximately 22%-30% of cognitively normal patients
demonstrating detectable cortical amyloid tracer uptake.
Uptake in cognitively normal patients is typically low, and
usually discernible from AD.132,159,168
Although only recently available, the clinical use of amyloidimaging agents remains limited. The Society of Nuclear
Medicine and Molecular Imaging and the Alzheimers Association have proposed appropriateness criteria, identifying
3 indications where clinical amyloid imaging may be most
useful.169 First, testing may benet patients with persistent or
progressive but unexplained MCI. Second, patients who may
have AD but have an atypical or mixed course. Lastly, amyloid
imaging may prove benecial in patients with early onset but
progressive dementia.142 A further consideration is that
although recent phase 3 clinical trials of antiamyloid immunotherapy agents did not show improvement in cognitive
scores of patients with Alzheimer disease, it remains possible
that early treatment with these or similar agents may prove to
have disease-modifying effects.170 In this setting, amyloidimaging agents could be used to identify patients who may
benet from such intervention.
The consensus paper by Johnson et al. further identied
situations where amyloid imaging is inappropriate in the
clinical setting. Primarily, these involved cases where the
clinical diagnosis of AD is highly certain or for asymptomatic
patients. In these cases, treatment decisions and clinical outcomes are not likely to benet. Unlike FDG-PET, amyloid
imaging does not allow evaluation for pathologic conditions
not characterized by amyloid accumulation, such as FTLD.
Although there is some evidence that amyloid tracer uptake
has prognostic efcacy for evaluation of progression from MCI
to AD,140 it appears that FDG-PET provides better prognosis
for cognitive function. Recent data indicates that amyloid
agents can detect increasing amyloid plaque in patients with
normal cognition before clinical symptoms arise, even 15 years
before plateau levels of amyloid plaque,171 and there is some
suggestion that PiB uptake may correlate with mild impaired
memory performance in healthy controls.159 However, potential use in cognitively normal patients could lead to unnecessary stress, testing, and potentially harmful treatment in
patients who would never progress to develop signicant
cognitive symptoms.
Figure 4 (F-18) orbetapir PET transaxial images. (A) Negative scan: in a cognitively normal patient, there is low cortical
uptake with preservation of gray-white discrimination. (B) Positive scan, indicating moderate to severe amyloid neuritic
plaque, here in a patient with Alzheimer dementia. There is cortical tracer uptake, which is in this case diffuse.
456
Figure 5 (F-18) uoropropyl-dihydrotetrabenazine (AV-133) PET transaxial images of the midbrain obtained in a healthy
control (A) and in a patient with Parkinson (B). Note the levels of VMAT2 are more depressed in the posterior aspect of the
striatum.
Emerging Indications
Parkinson Disease
Parkinson disease is a neurodegenerative disorder characterized
by loss of dopaminergic neurons in substantia nigra and the
striatum. It is the second most common neurodegenerative
disease after Alzheimer disease and thought to affect approximately 4.5 million worldwide, with that number estimated to
double by 2030.172 The clinical hallmark of Parkinsonian motor
symptoms includes tremor, rigidity, slowness of movement, and
postural instability.173 Although the SPECT tracer Ioupane has
recently become used in the United States to distinguish
Parkinsonian tremor from essential tremor, the cascade of events
leading to accumulation of the protein alpha-synuclein and
subsequent dopaminergic dysfunction remains unclear.174
Additionally, Ioupane has been successfully used in Europe
for dementia evaluation as patients with diffuse Lewy body
dementia have depressed levels of dopamine transporter; this
indication has not been approved in the United States.175,176
PET imaging of the brain using the radioligand (C-11)
tetrabenzine allowed for visualization of monoamine vesicular
transporter, a pathway fundamental for dopaminergic neurotransmission.177 Further evaluation led to the use of (C-11)
dihydrobenzine, which, as a VMAT2 marker, has been shown to
be very promising both as a biomarker for Parkinson disease178
and for dementia diagnosis.179 More appropriate for clinical use,
a uorinated derivative was developed, (18-F) uoropropyldihydrotetrabenazine, which has proved able to detect abnormal
monoamine neurotransmission depression in Parkinson disease180 and help distinguish diffuse Lewy body dementia from
Alzheimer disease.181 Figure 5 shows a comparison between (F18) uoropropyl-dihydrotetrabenazine PET brain images
obtained in a patient with Parkinson and a healthy control.
Conclusions
PET has spearheaded sciences efforts to unlock the workings
of the human brain in both normal and pathologic conditions.
Although technically challenging, requiring coordinated expertise in physics and instrumentation, radiochemistry, and
biology, PET remains poised to explore new frontiers in
neuroscience. PET will continue to play a prominent clinical
role in intractable epilepsy management and dementia diagnosis. As radiochemistry continues to further evolve and
complement our understanding of molecular and cellular
pathophysiology of disease, novel PET biomarkers of neurologic disease are just on the horizon.
457
References
458
48. Engel J Jr., Kuhl DE, Phelps ME, et al: Comparative localization of
epileptic foci in partial epilepsy by PCT and EEG. Ann Neurol 1982;
12:529-537
49. Engel J Jr., Kuhl DE, Phelps ME: Patterns of human local cerebral glucose
metabolism during epileptic seizures. Science 1982;218:64-66
50. Kim SH, Zubal G, Blumenfeld H: Epilepsy localization by ictal and
interictal SPECT, in, Van Heertum R, Tikofsky RS, Ichise M, (eds):
Functional Cerebral SPECT and PET Imaging. Philadelphia, PA, Wolters
Kluwer Health/Lippincott, Williams & Wilkins, 2010, pp 131-148
51. Engel J Jr.: Outcome with respect to epileptic seizures, in, Engel J Jr (ed):
Surgical Treatment of the Epilepsies. New York, NY, Raven Press, 1987,
pp 553-571
52. Foldvary N, Nashold B, Mascha E, et al: Seizure outcome after temporal
lobectomy for temporal lobe epilepsy: A Kaplan-Meier survival analysis.
Neurology 2000;54:630-634
53. Wieser HG, Blume WT, Fish D, et al: ILAE Commission Report.
Proposal for a new classication of outcome with respect to epileptic
seizures following epilepsy surgery. Epilepsia 2001;42:282-286
54. Carne RP, OBrien TJ, Kilpatrick CJ, et al: MRI-negative PET-positive
temporal lobe epilepsy: A distinct surgically remediable syndrome. Brain
2004;127(Pt 10):2276-2285
55. Kuba R, Tyrlikova I, Chrastina J, et al: MRI-negative PET-positive
temporal lobe epilepsy: Invasive EEG ndings, histopathology, and
postoperative outcomes. Epilepsy Behav 2011;22:537-541
56. LoPinto-Khoury C, Sperling MR, Skidmore C, et al: Surgical outcome in
PET-positive, MRI-negative patients with temporal lobe epilepsy.
Epilepsia 2012;53:342-348
57. Chassoux F, Rodrigo S, Semah F, et al: FDG-PET improves surgical
outcome in negative MRI Taylor-type focal cortical dysplasias. Neurology 2010;75:2168-2175
58. Thivard L, Bouilleret V, Chassoux F, et al: Diffusion tensor imaging can
localize the epileptogenic zone in nonlesional extra-temporal refractory
epilepsies when [(18)F]FDG-PET is not contributive. Epilepsy Res
2011;97:170-182
59. Cohen-Gadol AA, Wilhelmi BG, Collignon F, et al: Long-term outcome
of epilepsy surgery among 399 patients with nonlesional seizure foci
including mesial temporal lobe sclerosis. J Neurosurg 2006;104:
513-524
60. Rubi S, Setoain X, Donaire A, et al: Validation of FDG-PET/MRI
coregistration in nonlesional refractory childhood epilepsy. Epilepsia
2011;52:2216-2224
61. Salamon N, Kung J, Shaw SJ, et al: FDG-PET/MRI coregistration
improves detection of cortical dysplasia in patients with epilepsy.
Neurology 2008;71:1594-1601
62. Guerrini R, Barba C: Malformations of cortical development and aberrant
cortical networks: Epileptogenesis and functional organization. J Clin
Neurophysiol 2010;27:372-379
63. Benedek K, Juhasz C, Muzik O, et al: Metabolic changes of subcortical
structures in intractable focal epilepsy. Epilepsia 2004;45:1100-1105
64. Lin TW, de Aburto MA, Dahlbom M, et al: Predicting seizure-free status
for temporal lobe epilepsy patients undergoing surgery: Prognostic value
of quantifying maximal metabolic asymmetry extending over a specied
proportion of the temporal lobe. J Nucl Med 2007;48:776-782
65. Sakamoto S, Takami T, Tsuyuguchi N, et al: Prediction of seizure
outcome following epilepsy surgery: Asymmetry of thalamic glucose
metabolism and cerebral neural activity in temporal lobe epilepsy.
Seizure 2009;18:1-6
66. Newberg AB, Alavi A, Berlin J, et al: Ipsilateral and contralateral thalamic
hypometabolism as a predictor of outcome after temporal lobectomy for
seizures. J Nucl Med 2000;41:1964-1968
67. Joo EY, Hong SB, Han HJ, et al: Postoperative alteration of cerebral glucose metabolism in mesial temporal lobe epilepsy. Brain 2005;
128(Pt 8):1802-1810
68. Pearl PL, Gibson KM, Quezado Z, et al: Decreased GABA-A binding on
FMZ-PET in succinic semialdehyde dehydrogenase deciency. Neurology 2009;73:423-429
69. Jacobs KM, Graber KD, Kharazia VN, et al: Postlesional epilepsy: The
ultimate brain plasticity. Epilepsia 2000;41(suppl 6):S153-S161
459
114. Silverman DH, Small GW, Chang CY, et al: Positron emission
tomography in evaluation of dementia: Regional brain metabolism and
long-term outcome. J Am Med Assoc 2001;286:2120-2127 [Research
Support, Non-U.S. Govt Research Support, U.S. Govt, Non-P.H.S.
Research Support, U.S. Govt, P.H.S.]
115. Ossenkoppele R, Prins ND, Pijnenburg YAL, et al: Impact of molecular
imaging on the diagnostic process in a memory clinic. Alzheimer Demen
2012
116. Karow DS, McEvoy LK, Fennema-Notestine C, et al: Relative capability
of MR imaging and FDG PET to depict changes associated with
prodromal and early Alzheimer disease. Radiology 2010;256:932-942
[Research Support, N.I.H., Extramural Research Support, Non-U.S.
Govt Research Support, U.S. Govt, P.H.S.]
117. Liang WS, Reiman EM, Valla J, et al: Alzheimers disease is associated
with reduced expression of energy metabolism genes in posterior
cingulate neurons. Proc Natl Acad Sci U S A 2008;105:4441-4446
[Research Support, N.I.H., Extramural Research Support, Non-U.S.
Govt]
118. Liu X, Erikson C, Brun A: Cortical synaptic changes and gliosis in normal
aging, Alzheimers disease and frontal lobe degeneration. Dementia
1996;7:128-134 [Comparative Study Research Support, Non-U.S.
Govt]
119. Anderton BH, Callahan L, Coleman P, et al: Dendritic changes in
Alzheimers disease and factors that may underlie these changes. Prog
Neurobiol 1998;55:595-609 [Research Support, Non-U.S. Govt
Research Support, U.S. Govt, P.H.S. Review]
120. Zhou Y, Dougherty JH Jr., Hubner KF, et al: Abnormal connectivity in
the posterior cingulate and hippocampus in early Alzheimers disease
and mild cognitive impairment. Alzheimers Dement 2008;4:
265-270 [Research Support, Non-U.S. Govt]
121. McKhann GM, Knopman DS, Chertkow H, et al: The diagnosis of
dementia due to Alzheimers disease: Recommendations from the
National Institute on Aging-Alzheimers Association workgroups on
diagnostic guidelines for Alzheimers disease. Alzheimers Dement
2011;7:263-269 [Consensus Development Conference, NIH Research
Support, Non-U.S. Govt]
122. Jorm AF, Jolley D: The incidence of dementia: A meta-analysis.
Neurology 1998;51:728-733. [Meta-Analysis]
123. Mirra SS, Heyman A, McKeel D, et al: The Consortium to Establish a
Registry for Alzheimers Disease (CERAD). Part II. Standardization of
the neuropathologic assessment of Alzheimers disease. Neurology
1991;41:479-486 [Research Support, U.S. Govt, Non-P.H.S. Research
Support, U.S. Govt, P.H.S.]
124. Wilson RS, Weir DR, Leurgans SE, et al: Sources of variability
in estimates of the prevalence of Alzheimers disease in the United
States. Alzheimers Dement 2011;7:74-79 [Research Support, N.I.H.,
Extramural]
125. Jack CR Jr., Wiste HJ, Vemuri P, et al: Brain beta-amyloid measures and
magnetic resonance imaging atrophy both predict time-to-progression
from mild cognitive impairment to Alzheimers disease. Brain
2010;133:3336-3348 [Comparative Study Research Support, N.I.H.,
Extramural]
126. Albert MS, DeKosky ST, Dickson D, et al: The diagnosis of mild cognitive
impairment due to Alzheimers disease: Recommendations from the
National Institute on Aging-Alzheimers Association workgroups on
diagnostic guidelines for Alzheimers disease. Alzheimer Demen
2011;7:270-279
127. Wilson RS, Sue LE, Boyle PatriciaA, et al: Cognitive decline in prodromal
Alzheimer disease and mild cognitive impairment. Arch Neurol
2011;68:351-356
128. Plassman BL, Langa KM, Fisher GG, et al: Prevalence of cognitive
impairment without dementia in the United States. Ann Intern Med
2008;148:427-434 [Research Support, N.I.H., Extramural Research
Support, Non-U.S. Govt]
129. Petersen RC, Smith GE, et al: Mild cognitive impairment: Clinical
characterization and outcome. Arch Neurol 1999;56:303-308 [Research
Support, U.S. Govt, P.H.S.]
130. Gauthier S, Reisberg B, Zaudig M, et al: Mild cognitive impairment.
Lancet 2006;367:1262-1270
460
131. Petersen RC, Jack CR Jr.: Imaging and biomarkers in early Alzheimers
disease and mild cognitive impairment. Clin Pharmacol Ther
2009;86:438-441 [Research Support, N.I.H., Extramural Research
Support, Non-U.S. Govt]
132. Klunk WE: Amyloid imaging as a biomarker for cerebral betaamyloidosis and risk prediction for Alzheimer dementia. Neurobiol
Aging 2011;32(suppl 1):S20-S36 [Research Support, N.I.H., Extramural
Review]
133. Sperling RA, Aisen PS, Beckett LA, et al: Toward dening the preclinical
stages of Alzheimers disease: Recommendations from the National
Institute on Aging-Alzheimers Association workgroups on diagnostic
guidelines for Alzheimers disease. Alzheimers Dement 2011;7:280-292
[Consensus Development Conference, NIH Research Support, Non-U.S.
Govt]
134. Hoffman JM, Welsh-Bohmer KA, Hanson M, et al: FDG PET imaging in
patients with pathologically veried dementia. J Nucl Med
2000;41:1920-1928 [Research Support, Non-U.S. Govt Research
Support, U.S. Govt, P.H.S.]
135. Mosconi L, Tsui WH, Herholz K, et al: Multicenter standardized 18FFDG PET diagnosis of mild cognitive impairment, Alzheimers disease,
and other dementias. J Nucl Med 2008;49:390-398 [Multicenter Study
Research Support, N.I.H., Extramural Research Support, Non-U.S.
Govt]
136. Drzezga A, Lautenschlager N, Siebner H, et al: Cerebral metabolic
changes accompanying conversion of mild cognitive impairment into
Alzheimers disease: A PET follow-up study. Eur J Nucl Med Mol
Imaging 2003;30:1104-1113. [Clinical Trial Comparative Study Controlled Clinical Trial]
137. Landau SM, Harvey D, Madison CM, et al: Associations between
cognitive, functional, and FDG-PET measures of decline in AD and
MCI. Neurobiol Aging 2011;32:1207-1218
138. Patwardhan MB, McCrory DC, Matchar DB, et al: Alzheimer disease:
Operating characteristics of PETA meta-analysis. Radiology 2004;
231:73-80 [Meta-Analysis Research Support, U.S. Govt, P.H.S. Review]
139. Jagust W, Reed B, Mungas D, et al: What does uorodeoxyglucose PET
imaging add to a clinical diagnosis of dementia? Neurology
2007;69:871-877 [Comparative Study Evaluation Studies Research
Support, N.I.H., Extramural]
140. Zhang S, Han D, Tan X, et al: Diagnostic accuracy of 18 F-FDG and 11
C-PIB-PET for prediction of short-term conversion to Alzheimers
disease in subjects with mild cognitive impairment. Int J Clin Pract
2012;66:185-198. [Evaluation Studies Meta-Analysis Review]
141. Laforce R Jr., Buteau JP, Paquet N, et al: The value of PET in mild
cognitive impairment, typical and atypical/unclear dementias: A retrospective memory clinic study. Am J Alzheimers Dis Other Demen 2010
Jun;25:324-332 [Research Support, Non-U.S. Govt]
142. Jagust WJ, Landau SM, Shaw LM, et al: Relationships between
biomarkers in aging and dementia. Neurology 2009;73:1193-1199
143. Lo RY, Hubbard AE, Shaw LM, et al: Longitudinal change of biomarkers
in cognitive decline. Arch Neurol 2011;68:1257-1266 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Govt]
144. McKeith IG: Consensus guidelines for the clinical and pathologic
diagnosis of dementia with Lewy bodies (DLB): Report of the Consortium on DLB International Workshop. J Alzheimers Dis 2006;
9(suppl 3):417-423. [Congresses]
145. McKeith IG, Galasko D, Kosaka K, et al: Consensus guidelines for the
clinical and pathologic diagnosis of dementia with Lewy bodies (DLB):
Report of the consortium on DLB international workshop. Neurology
1996;47:1113-1124 [Guideline Practice Guideline Research Support,
Non-U.S. Govt Review]
146. Weisman D, McKeith I: Dementia with Lewy bodies. Semin Neurol
2007;27:42-47. [Review]
147. Minoshima S, Foster NL, Sima AA, et al: Alzheimers disease versus
dementia with Lewy bodies: Cerebral metabolic distinction with autopsy
conrmation. Ann Neurol 2001;50:358-365 [Research Support, U.S.
Govt, Non-P.H.S. Research Support, U.S. Govt, P.H.S.]
148. Ratnavalli E, Brayne C, Dawson K, et al: The prevalence of frontotemporal dementia. Neurology 2002;58:1615-1621 [Research Support,
Non-U.S. Govt]
168.
169.
170.
171.
172.
173.
174.
175.
176.
177.
178.
179.
180.
181.
461
182. Hall RC, Chapman MJ: Denition, diagnosis, and forensic implications
of postconcussional syndrome. Psychosomatics 2005;46:195-202.
[Review]
183. McKee AC, Stein TD, Nowinski CJ, et al: The spectrum of disease in
chronic traumatic encephalopathy. Brain 2013;136(Pt 1):43-64 [Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Govt
Research Support, U.S. Govt, Non-P.H.S.]
184. Hattori N, Huang SC, Wu HM, et al: Acute changes in regional cerebral
(18)F-FDG kinetics in patients with traumatic brain injury. J Nucl Med
2004;45:775-783 [Research Support, Non-U.S. GovtResearch Support,
U.S. Govt, Non-P.H.S.Research Support, U.S. Govt, P.H.S.]
185. Wu HM, Huang SC, Hattori N, et al: Selective metabolic reduction in
gray matter acutely following human traumatic brain injury. J Neurotrauma 2004;21:149-161 [Research Support, U.S. Govt, P.H.S.]
186. Ruff RM, Crouch JA, Troster AI, et al: Selected cases of poor
outcome following a minor brain trauma: Comparing neuropsychological and positron emission tomography assessment. Brain Inj
1994;8:297-308
187. Gross H, Kling A, Henry G, et al: Local cerebral glucose metabolism in
patients with long-term behavioral and cognitive decits following mild
traumatic brain injury. J Neuropsychiatry Clin Neurosci 1996;8:
324-334. [Clinical Trial]
188. Kato T, Nakayama N, Yasokawa Y, et al: Statistical image analysis of
cerebral glucose metabolism in patients with cognitive impairment
following diffuse traumatic brain injury. J Neurotrauma 2007;24:
919-926
189. Garcia-Panach J, Lull N, Lull JJ, et al: A voxel-based analysis of FDG-PET
in traumatic brain injury: Regional metabolism and relationship between
the thalamus and cortical areas. J Neurotrauma 2011;28:1707-1717
190. Lupi A, Bertagnoni G, Borghero A, et al: Relative hypermetabolism of
vermis cerebelli in traumatic brain injured patients studied with 18FDG
PET: A descriptor of brain damage and a possible predictor of outcome.
Curr Radiopharm 2011;4:167-175
191. de Souza LC, Lehericy S, Dubois B, et al: Neuroimaging in dementias.
Curr Opin Psychiatry 2012;25:473-479 [Research Support, Non-U.S.
Govt Review]
192. McKee AC, Cantu RC, Nowinski CJ, et al: Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury. J
Neuropathol Exp Neurol 2009;68:709-735 [Case Reports Research
Support, N.I.H., Extramural, Research Support, Non-U.S. Govt,
Research Support, U.S. Govt, Non-P.H.S., Review]
193. Small GW, Kepe V, Siddarth P, et al: PET scanning of brain tau in retired
national football league players: Preliminary ndings. Am J Geriatr
Psychiatry 2013;21:138-144