Skip to main content

Advertisement

SpringerLink
Log in

Pattern of extrapyramidal signs in Alzheimer’s disease

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Patients with Alzheimer’s disease (AD) often develop extrapyramidal signs (EPS), which increase in frequency as the disease progresses. We aimed to investigate the patterns of presentation of EPS in AD and their correlation with clinical and neuropathological features. 4284 subjects diagnosed with AD from the National Alzheimer’s Coordinating Center (NACC) database with at least one abnormal Unified Parkinson’s Disease Rating Scale (UPDRS) assessment were included. Individuals were assigned to a discovery sample and a sensitivity analysis sample (moderate and mild dementia, respectively) and a subset of subjects provided neuropathological data (n = 284). Individuals from the Washington Heights and Inwood Columbia Aging Project (WHICAP) served as validation sample. Patterns of presentation of EPS were identified employing categorical principal component analysis (CATPCA). Six principal components were identified in both mild and moderate AD samples: (I) hand movements, alternating movements, finger tapping, leg agility (“limbs bradykinesia”); (II) posture, postural instability, arising from chair, gait and body bradykinesia/hypokinesia (“axial”); (III) limb rigidity (“rigidity”); (IV) postural tremor; (V) resting tremor; (VI) speech and facial expression. Similar results were obtained in the WHICAP cohort. Individuals with hallucinations, apathy, aberrant night behaviors and more severe dementia showed higher axial and limb bradykinesia scores. “Limb bradykinesia” component was associated with a neuropathological diagnosis of Lewy body disease and “axial” component with reduced AD-type pathology. Patterns of EPS in AD show distinct clinical and neuropathological correlates; they share a pattern of presentation similar to that seen in Parkinson’s disease, suggesting common pathogenic mechanisms across neurodegenerative diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

TRACTRHD/LHD:

Postural tremor of right and left hand

TRESRHD/LHD:

Resting tremor of right and left hand

TAPSRT/LF:

Finger tapping of right and left hand

HANDMOVR/L:

Hand movements of right and left hand

LEGRT/LF:

Leg agility of right and left leg

RIG-NECK/DLORT/DLOLF/DUPRT/DUPLF:

Rigidity of neck, right leg, left leg, right arm and left arm

FACEXP:

Face expression

BRADYKIN:

Body bradykinesia and hypokinesia

ARISING:

Arising from chair

POSSTAB:

Postural stability

References

  1. Tosto G, Reitz C (2013) Genome-wide association studies in Alzheimer’s disease: a review. Curr Neurol Neurosci Rep 13:1–7

    Article  CAS  Google Scholar 

  2. Portet F, Scarmeas N, Cosentino S, Helzner EP, Stern Y (2009) Extrapyramidal signs before and after diagnosis of incident Alzheimer disease in a prospective population study. Arch Neurol 66:1120–1126

    PubMed Central  PubMed  Google Scholar 

  3. Mitchell SL (1999) Extrapyramidal features in Alzheimer’s disease. Age Ageing 28:401–409

    Article  CAS  PubMed  Google Scholar 

  4. Scarmeas N, Albert M, Brandt J, Blacker D, Hadjigeorgiou G, Papadimitriou A, Dubois B, Sarazin M, Wegesin D, Marder K, Bell K, Honig L, Stern Y (2005) Motor signs predict poor outcomes in Alzheimer disease. Neurology 64:1696–1703

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Fahn S ERM of the UDC (1987) Unified Parkinson’s Disease Rating Scale. Florham Park, Macmillan Health Care Information, NJ

    Google Scholar 

  6. Richards M, Marder K, Bell K, Dooneief G, Mayeux R, Stern Y (1991) Interrater reliability of extrapyramidal signs in a group assessed for dementia. Arch Neurol 48:1147–1149

    Article  CAS  PubMed  Google Scholar 

  7. Linting M, Meulman JJ, Groenen PJ, van der Koojj AJ (2007) Nonlinear principal components analysis: introduction and application. Psychol Methods 12:336–358

    Article  PubMed  Google Scholar 

  8. Beekly DL, Ramos EM, Lee WW, Deitrich WD, Jacka ME, Wu J, Hubbard JL, Koepsell TD, Morris JC, Kukull WA et al (2007) The National Alzheimer’s Coordinating Center (NACC) database: the uniform data set. Alzheimer Dis Assoc Disord 21:249–258

    Article  PubMed  Google Scholar 

  9. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) 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 34:939–940

    Article  CAS  PubMed  Google Scholar 

  10. Lee JH, Cheng R, Barral S, Reitz C, Medrano M, Lantigua R, Jiménez-Velazquez IZ, Rogaeva E, St George-Hyslop PH, Mayeux R (2011) Identification of novel loci for Alzheimer disease and replication of CLU, PICALM, and BIN1 in Caribbean Hispanic individuals. Arch Neurol 68:320–328

    PubMed Central  PubMed  Google Scholar 

  11. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  CAS  PubMed  Google Scholar 

  12. Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43:2412–2414

    Article  CAS  PubMed  Google Scholar 

  13. Hyman BT, Trojanowski JQ (1997) Editorial on consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56:1095–1097

    Article  CAS  PubMed  Google Scholar 

  14. McKeith I, Dickson D, Lowe J, Emre M, O’brien J, Feldman H, Cummings J, Duda J, Lippa C, Perry E et al (2005) Diagnosis and management of dementia with Lewy bodies Third report of the DLB consortium. Neurology 65:1863–1872

    Article  CAS  PubMed  Google Scholar 

  15. Linting M, van der Kooij A (2012) Nonlinear principal components analysis with CATPCA: a tutorial. J Pers Assess 94:12–25

    Article  PubMed  Google Scholar 

  16. Muthén B, Kaplan D (1985) A comparison of some methodologies for the factor analysis of non-normal Likert variables. Br J Math Stat Psychol 38:171–189

    Article  Google Scholar 

  17. Markus MT (1994) Bootstrap confidence regions in nonlinear multivariate analysis. DSWO Press, Leiden University

    Google Scholar 

  18. Cattell RB (1966) The scree test for the number of factors. Multivar Behav Res 1:245–276

    Article  Google Scholar 

  19. Cota AA, Longman RS, Holden RR, Fekken GC (1993) Comparing different methods for implementing parallel analysis: a practical index of accuracy. Educ Psychol Measur 53:865–876

    Article  Google Scholar 

  20. Comrey AL, Lee HB (1992) A first course in factor analysis. Erlbaum, Hillsdale, NJ

  21. Cronbach LJ (1951) Coefficient alpha and the internal structure of tests. Psychometrika 16:297–334

    Article  Google Scholar 

  22. Kaiser HF (1958) The varimax criterion for analytic rotation in factor analysis. Psychometrika 23:187–200

    Article  Google Scholar 

  23. Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125:279–284

    Article  CAS  PubMed  Google Scholar 

  24. Graham JM, Sagar HJ (1999) A data-driven approach to the study of heterogeneity in idiopathic Parkinson’s disease: identification of three distinct subtypes. Mov Disord 14:10–20

    Article  CAS  PubMed  Google Scholar 

  25. Della Sala S, Lucchelli F, Spinnler H (1987) Ideomotor apraxia in patients with dementia of Alzheimer type. J Neurol 234:91–93

    Article  CAS  PubMed  Google Scholar 

  26. Helmich RC, Hallett M, Deuschl G, Toni I, Bloem BR (2012) Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits? Brain 135:3206–3226

    Article  PubMed Central  PubMed  Google Scholar 

  27. Stebbins GT, Goetz CG (1998) Factor structure of the Unified Parkinson’s Disease Rating Scale: motor examination section. Mov Disord 13:633–636

    Article  CAS  PubMed  Google Scholar 

  28. Vassar SD, Bordelon YM, Hays RD, Diaz N, Rausch R, Mao C, Vickrey BG (2012) Confirmatory factor analysis of the motor unified Parkinson’s disease rating scale. Parkinson’s Dis

  29. Stochl J, Boomsma A, Ruzicka E, Brozova H, Blahus P (2008) On the structure of motor symptoms of Parkinson’s disease. Mov Disord 23:1307–1312

    Article  PubMed  Google Scholar 

  30. Brakedal B, Tysnes O-B, Skeie GO, Larsen JP, Müller B (2014) The factor structure of the UPDRS motor scores changes during early Parkinson’s disease. Parkinsonism Relat Disord 20:617–621

    Article  PubMed  Google Scholar 

  31. Evans JR, Mason SL, Williams-Gray CH, Foltynie T, Trotter M, Barker RA (2011) The factor structure of the UPDRS as an index of disease progression in Parkinson’s disease. J Parkinson’s Dis 1:75–82

    Google Scholar 

  32. Colom-Cadena M, Gelpi E, Charif S, Belbin O, Blesa R, Marti MJ, Clarimón J, Lleó A (2013) Confluence of alpha-synuclein, tau, and beta-amyloid pathologies in dementia with Lewy bodies. J Neuropathol Exp Neurol 72:1203–1212

    Article  CAS  PubMed  Google Scholar 

  33. Selikhova M, Williams D, Kempster P, Holton J, Revesz T, Lees A (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132:2947–2957

    Article  CAS  PubMed  Google Scholar 

  34. Toledo JB, Cairns NJ, Da X, Chen K, Carter D, Fleisher A, Householder E, Ayutyanont N, Roontiva A, Bauer RJ et al (2013) Clinical and multimodal biomarker correlates of ADNI neuropathological findings. Acta Neuropathol Commun 1:65

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The NACC database is funded by the NIA/NIH Grant U01 AG016976. NACC data were contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI David Teplow, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP) and P50 AG005681 (PI John Morris, MD). Dr. Tosto was supported by the DoD Grant W81XWH-12-1-0013. Dr. Tosto had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Tosto, Ms. Monsell, Dr. Hawes and Dr. Mayeux report no disclosures.

Author information

Authors and Affiliations

  1. The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA

    Giuseppe Tosto & Richard Mayeux

  2. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Giuseppe Tosto & Richard Mayeux

  3. Department of Neurology, College of Physicians and Surgeons, Columbia University and the New York Presbyterian Hospital, New York, NY, USA

    Richard Mayeux

  4. National Alzheimer’s Coordinating Center, University of Washington, Seattle, USA

    Sarah E. Monsell & Stephen E. Hawes

  5. Department of Epidemiology, University of Washington, Seattle, USA

    Stephen E. Hawes

  6. 630 W. 168th St., P&S Box 16, New York, NY, 10032, USA

    Richard Mayeux

Authors
  1. Giuseppe Tosto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah E. Monsell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen E. Hawes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard Mayeux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard Mayeux.

Ethics declarations

Conflicts of interest

None.

Ethical standards

Studies have been approved by the Institutional Review Boards and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tosto, G., Monsell, S.E., Hawes, S.E. et al. Pattern of extrapyramidal signs in Alzheimer’s disease. J Neurol 262, 2548–2556 (2015). https://doi.org/10.1007/s00415-015-7886-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-015-7886-1

Keywords

Search

Navigation