Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Case report

Applied multimodal diagnostics in a case of presenile dementia

Authors: Sonja Schönecker, Matthias Brendel, Marion Huber, Christian Vollmar, Hans-Juergen Huppertz, Stefan Teipel, Nobuyuki Okamura, Johannes Levin, Axel Rominger, Adrian Danek

Published in: BMC Neurology | Issue 1/2016

Login to get access

Abstract

Background

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. The possibility of disease-modifying strategies has evoked a need for early and accurate diagnosis. To improve the accuracy of the clinical diagnosis of AD, biomarkers like cerebrospinal fluid (CSF) and neuroimaging techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) have been incorporated into the diagnostic guidelines of AD.

Case presentation

In this case report we outline in reference to one of our patients with presenile dementia the current approaches to the diagnosis of AD. The patient was a 59-year old woman presenting with progressive memory decline. CSF-Aβ42 was normal while P-tau was slightly increased. FDG-PET indicated a pattern typical for AD, amyloid-PET showed an extensive global amyloid load, and tau-PET depicted a pronounced hippocampal tracer accumulation. The MRI scan was rated as normal at routine diagnostics, however quantitative volumetric analysis revealed significant atrophy especially of the parietal lobe. The combination of biomarkers and neuroimaging techniques was therefore suggestive of an underlying AD pathology.

Conclusions

To enable early and accurate diagnosis of AD and thereby also patient recruitment for anti-tau or anti-β-amyloid therapeutic trials, a combination of biomarkers and neuroimaging techniques seems useful.
Literature
1.
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimer’s & Dementia. 2007;3(3):186–91.CrossRef
2.
3.
Jellinger KA. Neuropathology of Dementia Disorders. Journal of Alzheimer’s Disease & Parkinsonism. 2014;4:135.
4.
Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, et al. Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease. New England Journal of Medicine. 2012;367(9):795–804.CrossRefPubMedPubMedCentral
5.
Bergmans BA, De Strooper B. γ-secretases: from cell biology to therapeutic strategies. The Lancet Neurology. 2010;9(2):215–26.CrossRefPubMed
6.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R. 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. Alzheimer’s & Dementia. 2011;7(3):263–9.CrossRef
7.
Huppertz H-J, Kroell-Seger J, Kloeppel S, Ganz RE, Kassubek J. Intra- and interscanner variability of automated voxel-based volumetry based on a 3D probabilistic atlas of human cerebral structures. NeuroImage. 2010;49(3):2216–24.CrossRefPubMed
8.
Frings L, Yew B, Flanagan E, Lam BY, Hull M, Huppertz HJ, Hodges JR, Hornberger M. Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer’s disease. PloS one. 2014;9(3):e90814.CrossRefPubMedPubMedCentral
9.
Teipel SJ, Reuter S, Stieltjes B, Acosta-Cabronero J, Ernemann U, Fellgiebel A, Filippi M, Frisoni G, Hentschel F, Jessen F, et al. Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study. Psychiatry research. 2011;194(3):363–71.CrossRefPubMed
10.
Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010. Journal of neuropathology and experimental neurology. 2012;71(4):266–73.CrossRefPubMedPubMedCentral
11.
McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65(12):1863–72.CrossRefPubMed
12.
Rascovsky K, Hodges JR, Knopman D, Mendez M, Kramer JH, Neuhause J, van Swieten JC. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.CrossRefPubMedPubMedCentral
13.
Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14.CrossRefPubMedPubMedCentral
14.
Montenigro PH, Baugh CM, Daneshvar DH, Mez J, Budson AE, Au R, Katz DI, Cantu RC, Stern RA. Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome. Alzheimers Res Ther. 2014;6(5):68.CrossRefPubMedPubMedCentral
15.
Clark CM, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, Morris JC, McKeel DW, Farlow M, Weitlauf SL. Cerebrospinal fluid tau and β-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses? Archives of neurology. 2003;60(12):1696–702.CrossRefPubMed
16.
Slaets S, Le Bastard N, Theuns J, Sleegers K, Verstraeten A, De Leenheir E, Luyckx J, Martin J-J, Van Broeckhoven C, Engelborghs S. Amyloid pathology influences aβ1-42 cerebrospinal fluid levels in dementia with lewy bodies. Journal of Alzheimer’s Disease. 2013;35(1):137–46.PubMed
17.
Koopman K, Le Bastard N, Martin JJ, Nagels G, De Deyn PP, Engelborghs S. Improved discrimination of autopsy-confirmed Alzheimer’s disease (AD) from non-AD dementias using CSF P-tau(181P). Neurochemistry international. 2009;55(4):214–8.CrossRefPubMed
18.
Bian H, Van Swieten JC, Leight S, Massimo L, Wood E, Forman M, Moore P, de Koning I, Clark CM, Rosso S, et al. CSF biomarkers in frontotemporal lobar degeneration with known pathology. Neurology. 2008;70(19 Pt 2):1827–35.CrossRefPubMedPubMedCentral
19.
Toledo JB, Brettschneider J, Grossman M, Arnold SE, Hu WT, Xie SX, Lee VM-Y, Shaw LM, Trojanowski JQ. CSF biomarkers cutoffs: the importance of coincident neuropathological diseases. Acta neuropathologica. 2012;124(1):23–35.CrossRefPubMedPubMedCentral
20.
Vemuri P, Simon G, Kantarci K, Whitwell JL, Senjem ML, Przybelski SA, Gunter JL, Josephs KA, Knopman DS, Boeve BF, et al. Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND. NeuroImage. 2011;55(2):522–31.CrossRefPubMed
21.
Rabinovici G, Seeley W, Kim E, Gorno-Tempini M, Rascovsky K, Pagliaro T, Allison S, Halabi C, Kramer J, Johnson J. Distinct MRI atrophy patterns in autopsy-proven Alzheimer’s disease and frontotemporal lobar degeneration. American journal of Alzheimer’s disease and other dementias. 2008;22(6):474–88.CrossRef
22.
Burton E, Barber R, Mukaetova-Ladinska E, Robson J, Perry R, Jaros E, Kalaria R, O’Brien J. Medial temporal lobe atrophy on MRI differentiates Alzheimer’s disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis. Brain. 2009;132(1):195–203.CrossRefPubMed
23.
Kantarci K, Lowe VJ, Boeve BF, Weigand SD, Senjem ML, Przybelski SA, Dickson DW, Parisi JE, Knopman DS, Smith GE. Multimodality imaging characteristics of dementia with Lewy bodies. Neurobiology of aging. 2012;33(9):2091–105.CrossRefPubMed
24.
McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. Journal of neuropathology and experimental neurology. 2009;68(7):709–35.CrossRefPubMedPubMedCentral
25.
Minoshima S, Foster NL, Sima AA, Frey KA, Albin RL, Kuhl DE. Alzheimer’s disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Annals of neurology. 2001;50(3):358–65.CrossRefPubMed
26.
Albin R, Minoshima S, D’Amato C, Frey K, Kuhl D, Sima A. Fluoro-deoxyglucose positron emission tomography in diffuse Lewy body disease. Neurology. 1996;47(2):462–6.CrossRefPubMed
27.
Foster NL, Heidebrink JL, Clark CM, Jagust WJ, Arnold SE, Barbas NR, DeCarli CS, Turner RS, Koeppe RA, Higdon R, et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer’s disease. Brain. 2007;130(Pt 10):2616–35.CrossRefPubMed
28.
Bacskai BJ, Frosch MP, Freeman SH, Raymond SB, Augustinack JC, Johnson KA, Irizarry MC, Klunk WE, Mathis CA, DeKosky ST. Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Archives of neurology. 2007;64(3):431–4.CrossRefPubMed
29.
Rabinovici G, Rosen H, Alkalay A, Kornak J, Furst A, Agarwal N, Mormino E, O’Neil J, Janabi M, Karydas A. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology. 2011;77(23):2034–42.CrossRefPubMedPubMedCentral
30.
Ghetti B, Oblak AL, Boeve BF, Johnson KA, Dickerson BC, Goedert M. Invited review: Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging. Neuropathology and applied neurobiology. 2015;41(1):24–46.CrossRefPubMedPubMedCentral
31.
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta neuropathologica. 1991;82(4):239–59.CrossRefPubMed
32.
Salmon D. Disorders of memory in Alzheimer’s disease. In: Cermak L, editor. Handbook of neuropsychology, Vol 2: Memory and its disorders. Volume 2, edn. Amsterdam: Elsevier; 2000. p. 155–95.
33.
Seppala TT, Nerg O, Koivisto AM, Rummukainen J, Puli L, Zetterberg H, Pyykko OT, Helisalmi S, Alafuzoff I, Hiltunen M, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology. 2012;78(20):1568–75.CrossRefPubMed
34.
Landau SM, Lu M, Joshi AD, Pontecorvo M, Mintun MA, Trojanowski JQ, Shaw LM, Jagust WJ. Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β‐amyloid. Annals of neurology. 2013;74(6):826–36.CrossRefPubMedPubMedCentral
35.
Blennow K, Zetterberg H, Minthon L, Lannfelt L, Strid S, Annas P, Basun H, Andreasen N. Longitudinal stability of CSF biomarkers in Alzheimer’s disease. Neuroscience letters. 2007;419(1):18–22.CrossRefPubMed
36.
Mollenhauer B, Bibl M, Wiltfang J, Steinacker P, Ciesielczyk B, Neubert K, Trenkwalder C, Otto M. Total tau protein, phosphorylated tau (181p) protein, beta-amyloid(1–42), and beta-amyloid(1–40) in cerebrospinal fluid of patients with dementia with Lewy bodies. Clinical chemistry and laboratory medicine. 2006;44(2):192–5.CrossRefPubMed
37.
Sexton CE, Mackay CE, Lonie JA, Bastin ME, Terrière E, O’Carroll RE, Ebmeier KP. MRI correlates of episodic memory in Alzheimer’s disease, mild cognitive impairment, and healthy aging. Psychiatry Research: Neuroimaging. 2010;184(1):57–62.CrossRefPubMed
38.
Herholz K, Carter SF, Jones M. Positron emission tomography imaging in dementia. The British journal of radiology. 2007;80 Spec No 2:S160–167.CrossRefPubMed
39.
Provenzano FA, Jordan B, Tikofsky RS, Saxena C, Van Heertum RL, Ichise M. F-18 FDG PET imaging of chronic traumatic brain injury in boxers: a statistical parametric analysis. Nuclear medicine communications. 2010;31(11):952–7.CrossRefPubMed
40.
Peskind ER, Petrie EC, Cross DJ, Pagulayan K, McCraw K, Hoff D, Hart K, Yu CE, Raskind MA, Cook DG, et al. Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms. NeuroImage. 2011;54 Suppl 1:S76–82.CrossRefPubMed
41.
Jagust W, Reed B, Mungas D, Ellis W, Decarli C. What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? Neurology. 2007;69(9):871–7.CrossRefPubMed
42.
Landau S, Harvey D, Madison C, Reiman E, Foster N, Aisen P, Petersen R, Shaw L, Trojanowski J, Jack C. Comparing predictors of conversion and decline in mild cognitive impairment. Neurology. 2010;75(3):230–8.CrossRefPubMedPubMedCentral
43.
Donaghy P, Thomas AJ, O’Brien JT. Amyloid PET Imaging in Lewy body disorders. The American journal of geriatric psychiatry. 2015;23(1):23–37.CrossRefPubMed
44.
Rowe C, Ng S, Ackermann U, Gong S, Pike K, Savage G, Cowie T, Dickinson K, Maruff P, Darby D. Imaging β-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718–25.CrossRefPubMed
45.
Engler H, Santillo AF, Wang SX, Lindau M, Savitcheva I, Nordberg A, Lannfelt L, Langstrom B, Kilander L. In vivo amyloid imaging with PET in frontotemporal dementia. Eur J Nucl Med Mol Imaging. 2008;35(1):100–6.CrossRefPubMed
46.
McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, Lee HS, Wojtowicz SM, Hall G, Baugh CM, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(Pt 1):43–64.CrossRefPubMed
47.
Curtis C, Gamez JE, Singh U, Sadowsky CH, Villena T, Sabbagh MN, Beach TG, Duara R, Fleisher AS, Frey KA, et al. Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. JAMA neurology. 2015;72(3):287–94.CrossRefPubMed
48.
Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, Senda K, Murayama S, Ishii K, Takao M. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer disease: Phase 3 study. Alzheimer’s & Dementia. 2015;11(8):964-74
49.
Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. The Lancet Neurology. 2012;11(8):669–78.CrossRefPubMed
50.
Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ, Castellani RJ, Crain BJ, Davies P, Del Tredici K, et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. Journal of neuropathology and experimental neurology. 2012;71(5):362–81.CrossRefPubMedPubMedCentral
51.
Gomperts SN, Marquie M, Locascio JJ, Bayer S, Johnson KA, Growdon JH. PET Radioligands Reveal the Basis of Dementia in Parkinson’s Disease and Dementia with Lewy Bodies. Neurodegenerative Diseases. 2016;16(1–2):118–24.PubMed
52.
Mitsis EM, Riggio S, Kostakoglu L, Dickstein DL, Machac J, Delman B, Goldstein M, Jennings D, D’Antonio E, Martin J, et al. Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury. Translational psychiatry. 2014;4:e441.CrossRefPubMedPubMedCentral
53.
Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. Journal of Nuclear Medicine. 1995;36(7):1238–48.PubMed
Metadata
Title
Applied multimodal diagnostics in a case of presenile dementia
Authors
Sonja Schönecker
Matthias Brendel
Marion Huber
Christian Vollmar
Hans-Juergen Huppertz
Stefan Teipel
Nobuyuki Okamura
Johannes Levin
Axel Rominger
Adrian Danek
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0647-7

Other articles of this Issue 1/2016

BMC Neurology 1/2016 Go to the issue

Technical advance

Ultrasound-guided botulinum toxin A injection in the treatment of belly dancer’s dyskinesia

Research article

Association of serum myokines and aerobic exercise training in patients with spinal cord injury: an observational study

Research article

MRI utility in the detection of disease activity in clinically stable patients with multiple sclerosis: a retrospective analysis of a community based cohort

Case report

Posterior reversible encephalopathy as the first manifestation of Bickerstaff’s brainstem encephalitis

Research article

Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls

Research article

Experiences and perspectives of patients with post-polio syndrome and therapists with exercise and cognitive behavioural therapy