0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

REGULAR ARTICLES   |    
Association Between Clinical Measures and Florbetapir F18 PET Neuroimaging in Mild or Moderate Alzheimer’s Disease Dementia
Michael M. Witte, Ph.D.; Paula Trzepacz, M.D.; Michael Case, M.S.; Peng Yu, Ph.D.; Helen Hochstetler, Pharm.D.; Mitchell Quinlivan, Ph.D.; Karen Sundell, B.S.; David Henley, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2014;26:214-220. doi:10.1176/appi.neuropsych.12120402
View Author and Article Information

From the Department of Neurosciences, Lilly USA, LLC, Indianapolis, IN (MMW, PT, MC, PY, HH); the Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN (PT, DH); Eli Lilly Australia, West Ryde, Australia (MQ); and Lilly Research Laboratories, Indianapolis, IN (KS, DH).

Send correspondence to Dr. Witte; e-mail: witte_michael_m@lilly.com

Copyright © 2014 by the American Psychiatric Association

Received December 18, 2012; Revised March 21, 2013; Accepted April 22, 2013.

Abstract

Clinical diagnosis of Alzheimer’s disease (AD) is challenging, with 20% or more of patients misdiagnosed, even by expert clinicians. The authors conducted a retrospective, cross-sectional analysis comparing baseline neuropsychiatric and other clinical characteristics in 199 expert-diagnosed mild and moderate AD dementia patients participating in industry-sponsored clinical trials of an investigational therapy, where 18% lacked florbetapir positron emission tomography (PET) evidence of AD neuropathology. Significant differences were found only for cognition and ApoE ε4 status, but the large degree of score overlap would preclude using these measures to predict AD misdiagnosis. This study highlights the value of amyloid PET when evaluating patients with seemingly typical AD.

Abstract Teaser
Figures in this Article

Your Session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 1. Representative FBP-PET Images for Two Subjects

FBP-PET positive scan (top row, SUVR=2.13) and FBP-PET negative scan (bottom row, SUVR=1.01), show a difference of florbetapir uptake between the subjects in lateral temporal, precuneus, lateral frontal, and posterior cingulate cortical regions. Prespecified SUVR threshold of 1.10 (with respect to cerebellum as a reference region) was used to define florbetapir positivity. Transverse (left) and sagittal images (right) are shown at the same level in both subjects.

Anchor for Jump
TABLE 1.Demographic, Neuropsychiatric, Cognitive, Genomic, and FBP-PET Composite SUVR Values for Patients with Clinically Diagnosed Mild or Moderate Dementia Due to AD, Categorized by FBP-PET Scan Resulta
Table Footer Note

Data are expressed as means±SD (range) or within group n (%) as appropriate and p values are between positive and negative scan groups. AD: Alzheimer’s disease; ADAS-Cog14: Alzheimer’s disease assessment scale – cognitive subscale 14-item version; ADCS-ADL: Alzheimer’s disease cooperative study activities of daily living inventory; CDR-SB: clinical dementia rating – sum of boxes; FBP: 18fluorine-labelled florbetapir; GDS: geriatric depression scale; MMSE: mini mental-state exam; NPI: neuropsychiatric inventory; PET: positron emission tomography; SD: standard deviation; SUVR: standardized uptake value ratio.

Table Footer Note

a FBP-PET scans were categorized as either positive or negative for the presence of abnormal levels of Aβ plaque using a cutoff value of ≥1.1.

Table Footer Note

b Frequencies are analyzed using Fisher’s exact test, means by analysis-of-variance.

+

References

Mayeux  R;  Saunders  AM;  Shea  S  et al; Alzheimer’s Disease Centers Consortium on Apolipoprotein E and Alzheimer’s Disease:  Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease.  N Engl J Med 1998; 338:506–511
[CrossRef] | [PubMed]
 
Beach  TG;  Monsell  SE;  Phillips  LE  et al:  Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010.  J Neuropathol Exp Neurol 2012; 71:266–273
[CrossRef] | [PubMed]
 
McKhann  G;  Drachman  D;  Folstein  M  et al:  Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease.  Neurology 1984; 34:939–944
[CrossRef] | [PubMed]
 
McKhann  GM;  Knopman  DS;  Chertkow  H  et al:  The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease.  Alzheimers Dement 2011; 7:263–269
[CrossRef] | [PubMed]
 
Jack  CR  Jr;  Albert  MS;  Knopman  DS  et al:  Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease.  Alzheimers Dement 2011; 7:257–262
[CrossRef] | [PubMed]
 
Clark  CM;  Schneider  JA;  Bedell  BJ  et al; AV45-A07 Study Group:  Use of florbetapir-PET for imaging beta-amyloid pathology.  JAMA 2011; 305:275–283
[CrossRef] | [PubMed]
 
Clark  CM;  Pontecorvo  MJ;  Beach  TG  et al; AV-45-A16 Study Group:  Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study.  Lancet Neurol 2012; 11:669–678
[CrossRef] | [PubMed]
 
Landau  SM;  Breault  C;  Joshi  AD  et al; Alzheimer’s Disease Neuroimaging Initiative:  Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods.  J Nucl Med 2013; 54:70–77
[CrossRef] | [PubMed]
 
Carlson  C;  Estergard  W;  Oh  J  et al:  Prevalence of asymptomatic vasogenic edema in pretreatment Alzheimer’s disease study cohorts from phase 3 trials of semagacestat and solanezumab.  Alzheimers Dement 2011; 7:396–401
[CrossRef] | [PubMed]
 
Rosen  WG;  Mohs  RC;  Davis  KL:  A new rating scale for Alzheimer’s disease.  Am J Psychiatry 1984; 141:1356–1364
[PubMed]
 
Mohs  RC;  Knopman  D;  Petersen  RC  et al:  Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer’s Disease Assessment Scale that broaden its scope. The Alzheimer’s Disease Cooperative Study.  Alzheimer Dis Assoc Disord 1997; 11(Suppl 2):S13–S21
[CrossRef] | [PubMed]
 
Galasko  D;  Bennett  D;  Sano  M  et al:  An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study.  Alzheimer Dis Assoc Disord 1997; 11(Suppl 2):S33–S39
[CrossRef] | [PubMed]
 
Galasko  D;  Kershaw  PR;  Schneider  L  et al:  Galantamine maintains ability to perform activities of daily living in patients with Alzheimer’s disease.  J Am Geriatr Soc 2004; 52:1070–1076
[CrossRef] | [PubMed]
 
Berg  L;  Miller  JP;  Baty  J  et al:  Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention.  Ann Neurol 1992; 31:242–249
[CrossRef] | [PubMed]
 
Morris  JC:  The Clinical Dementia Rating (CDR): current version and scoring rules.  Neurology 1993; 43:2412–2414
[CrossRef] | [PubMed]
 
Folstein  MF;  Folstein  SE;  McHugh  PR:  “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res 1975; 12:189–198
[CrossRef] | [PubMed]
 
Cummings  JL;  Mega  M;  Gray  K  et al:  The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia.  Neurology 1994; 44:2308–2314
[CrossRef] | [PubMed]
 
Aalten  P;  Verhey  FR;  Boziki  M  et al:  Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I.  Dement Geriatr Cogn Disord 2007; 24:457–463
[CrossRef] | [PubMed]
 
Aalten  P;  Verhey  FR;  Boziki  M  et al:  Consistency of neuropsychiatric syndromes across dementias: results from the European Alzheimer Disease Consortium. Part II.  Dement Geriatr Cogn Disord 2008; 25:1–8
[CrossRef] | [PubMed]
 
Dennehy  EB;  Kahle-Wrobleski  K;  Sarsour  K  et al:  Derivation of a brief measure of agitation and aggression in Alzheimer’s disease.  Int J Geriatr Psychiatry 2013; 28:182–189
[CrossRef] | [PubMed]
 
Trzepacz  PT;  Saykin  A;  Bhamditipati  P  et al:  Subscale validation of the neuropsychiatric inventory questionnaire: Comparison of Alzheimer’s disease neuroimaging initiative and national Alzheimer’s coordinating center cohorts.  Am J Geriatr Psychiatry 2013; 21:607–622
[CrossRef] | [PubMed]
 
Sheikh  J;  Yesavage  J:  Geriatric Depression Scale (GDS): recent evidence and development of the shorter version.  Clin Gerontol 1986; 5:165–173
[CrossRef]
 
Choi  SR;  Golding  G;  Zhuang  Z  et al:  Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain.  J Nucl Med 2009; 50:1887–1894
[CrossRef] | [PubMed]
 
Rosenberg  PB;  Wong  DF;  Edell  SL  et al:  Cognition and amyloid load in alzheimer disease imaged with florbetapir F 18 (AV-45) positron emission tomography.  Am J Geriatr Psychiatry 2013; 2:272–278
 
Landau  SM;  Mintun  MA;  Joshi  AD  et al; Alzheimer’s Disease Neuroimaging Initiative:  Amyloid deposition, hypometabolism, and longitudinal cognitive decline.  Ann Neurol 2012; 72:578–586
[CrossRef] | [PubMed]
 
Sperling R, Salloway S, Raskind M, et al: Bapineuzumab phase 3 trials in mild to moderate Alzheimer’s disease dementia in apolipoprotein E e4 carriers (study 302) and non-carriers (study 301) 2012; http://www.ctad.fr/07-download/Congres2012/PressRelease/Final-Sperling-CTAD-Presentation-10-29-12.pdf; accessed Feb 11, 2013
 
Johnson  KA;  Sperling  RA;  Gidicsin  CM  et al:  Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer’s disease dementia, mild cognitive impairment, and normal aging.  Alzheimers Dement 2013; 9(Suppl 5):S72–S83
[CrossRef] | [PubMed]
 
Fleisher  AS;  Chen  K;  Liu  X  et al:  Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease.  Arch Neurol 2011; 68:1404–1411
[CrossRef] | [PubMed]
 
References Container
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Books
APA Practice Guidelines > Chapter 0.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 11.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 11.  >
Textbook of Traumatic Brain Injury, 2nd Edition > Chapter 3.  >
Textbook of Traumatic Brain Injury, 2nd Edition > Chapter 3.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
APA Guidelines
PubMed Articles