Statement  of  Intended  Use/Disclaimers  All  informa,on,  data,  and  material  contained,  presented,  or  provided  in  this  program  /  presenta,on  (“Informa,on”)  is  for  general  informa,on  purposes  only   and   solely   the  opinion  of   the   authors   and  presenters.   The   Informa,on   should  not  be   construed  or  intended  as  providing  personalized  medical  or  legal  advice.  The  Informa,on  is  not  necessarily  considered  mainstream  health  care.    It  is  leP  to  the  discre,on  and  judgment  and  is  the  sole  responsibility  of  the  recipient  of  the  Informa,on  to  determine  if  products,  procedures,  treatments,  tests,  and  therapies  described  are  appropriate  for  the  client.      Neither  the  speakers  nor  the  sponsors  of  Func,onal  Neurology  Seminars  can  be  held  responsible  for  the  Informa,on,  opinions,  or  any   inadvertent   errors   or   omissions   in   the   prepara,on   or   presenta,on   of   the   Informa,on.   The   Informa,on   should   not   be  construed  as  a  claim  regarding  any  procedure,  treatment,  therapy,  test,  or  product.      It  is  the  sole  responsibility  of  the  recipient  of  this  Informa,on  to  comply  with  local,  state,  and  federal  laws  regarding  the  use  of  such  Informa,on,  as  it  relates  to  the  scope  and  type  of  user’s  prac,ce.    It  is  the  concern  of  the  Department  of  Health  and  Human  Services  that  no  homeopathic  and/or  nutri,onal  supplement  be  used  to  replace  established,  conven,onal  medical  approaches,  especially  in  cases  of  emergencies  or  serious  or  life-­‐threatening  diseases,  or  condi,ons.    Func,onal  Neurology  Seminars  shares  in  this  concern,  as  replacing  conven,onal  treatment  with  homeopathic  and/or  nutri,onal  supplements,  especially  in  serious  cases,  may  deprive  the  client  of  necessary  treatment  thereby  causing  harm  and  could  also  pose  a  major  legal  liability  for  the  healthcare  professional  involved.  The  Informa,on  has  not  been  evaluated  by  the  Food  and  Drug  Administra,on.  Any  nutri,onal  product  or  procedure   reported   in   this   presenta,on   is   not   intended   to   diagnose,   treat,   cure,   or   prevent   disease.     Various   forms   of   care  described   in   the   FNS   seminar   series   should   not   be   used   to   replace   conven,onal   neurological   care   or   replace   other   forms   of  medically  necessary  care.      Dr.  Da,s  Kharrazian  has  the  following  financial  interests.  He  is  a  member  of  Apex  Energe,cs,  Inc.'s  Scien,fic  Advisory  Board,  is  a  paid  consultant  to  Apex  Energe,cs,  and  receives  royal,es  on  the  sale  of  DVDs  and  CDs.    Dr.  Kharrazian  is  also  a  member  of  the  editorial  board  of  the  Journal  of  Func,onal  Neurology,  Rehabilita,on,  and  Ergonomics.    He  receives  no  financial  compensa,on  for  his   par,cipa,on   on   this   board.     Dr.   Kharrazian   serves   on   the   Curriculum   Advisory   Commi\ee   of   the   Ins,tute   for   Func,onal  Medicine.    He  receives  no  financial  compensa,on  for  his  par,cipa,on  on  this  commi\ee.    Dr.  Brock  has  the  following  financial  interests.    Dr.  Brock  is  a  paid  employee  of  Cerebrum  Health  Centers  and  owner  and  operator  or   Drbrocklectures.com   and   does   consul,ng   work   for   various   clinics.       Dr.   Brock   is   a   paid   instructor   for   the   Academy   of  Osteopathic  Science,  unpaid  vice  president  of   the   Interna,onal  Associa,on  of  Func,onal  Neurology  and  Rehabilita,on,  unpaid  member   of   the   human   council   of   human   func,on   and   an   unpaid   board   member   of   the   American   Associa,on   of   Integra,ve  Medicine.    Dr.  Brock  is    a  paid  lecturer  for  Apex  Energe,cs.    Dr.  Brock  has  been  engaged  as  an  industry  expert  by  Moleculara  Laboratories  to  assist  in  the  development  of  educa,onal  lectures  and  to  educate  healthcare  prac,,oners  in  its  technology  and  the  applica,on  of  its  tes,ng.    As  such,  he  receives  commissions  from  Moleculara  as  permi\ed  by  and  in  compliance  with  federal  and  state  laws,  codes  and  regula,ons,  including  Stark  and  other  an,-­‐kickback  provisions.    He  is  not  an  employee  of  Moleculara  and  does  not  own  any  stock.            Dr.  Kharrazian  has  been  engaged  as  an  industry  expert  by  Cyrex  Laboratories,  LLC  to  assist  in  the  development  of  clinical  assays  and  to  educate  healthcare  prac,,oners  in  its  technology  and  the  applica,on  of  its  arrays.    As  such,  he  receives  commissions  from  Cyrex   as   permi\ed   by   and   in   compliance  with   federal   and   state   laws,   codes   and   regula,ons,   including   Stark   and   other   an,-­‐kickback  provisions.    He   is   not   an  employee  of  Cyrex   and  does  not  own  any   stock.    All  marks   and   their   use   are   thereby  duly  governed  by  the  respec,ve  owners  and  any  and  all   rights   in  connec,on  with  those  marks  are  en,rely  reserved.  The  presenter  receives  a  speaker’s  fee  and  is  reimbursed  for  his/her  travel  and  related  accommoda,ons  by  the  sponsor,  Apex  Energe,cs,  Inc.    Dr.  Kharrazian  nor  Dr.  Brock  have  any  financial  interests  in  Laboratory  Corpora,on  of  America,  Quest  Diagnos,cs,  Incorporated,  Diagnos-­‐Techs,   Inc.,  Principal  Lab,   Inc,  Metametrix,   Inc.,  Metabolic  Solu,ons  Development  Company,  LLC,   Immunosciences  Lab,  Inc.,  RealTime  Laboratories,   Inc.,  Direct   Laboratory  Services,   Inc.,  or  Genova  Diagnos,cs  or  other   labs  men,oned   in   this   series  other  than  those  listed  in  this  disclaimer.        

3  

Dr.  Joel  Brandon  Brock      MSN,  BSN,  RN,  DC,  NP-­‐-­‐C,  DCM,  DCN,  DAAIM,  BCIM,  DCBCN,  DACNB,  FACNB,  FICC  

Dr.  Brandon  Brock  is  a  Cer,fied  Family  Nurse  Prac,,oner,  Chiropractor  and  a  func,onal  neurology  diplomate  with  mul,ple  clinical  interests,  including  Func,onal  Integra,ve  Neurology.    In  Dallas  Texas  he  serves  as  a  staff  clinician  at  Cerebrum  Health  Centers  and  does  work  at  Innova,ve  Health  and  Wellness  Group  and  Founda,on  Physicians  Group.  Along  with  being  a  clinician,  Dr.  Brock  has  a  passion  for  lecturing  and  providing  learners  with  didac,c  and  academic  skills  in  a  way  that  is  easy  to  digest,  comprehend  and  u,lize  in  a  clinical  seeng.  He  has  developed  thousands  of  mul,disciplinary  hours  of  curriculum  that  he  or  others    have  presented  pertaining  to  neurology,  nutri,on,  physical  diagnosis,  pharmacology,  immunology,  endocrinology,  and  this  has  impacted  students  of  mul,ple  educa,onal  and  clinical  backgrounds,  including  medical  doctors,  nurse    prac,,oners  and  chiropractors.    Offering  educa,onal  support  for  Physical  and  Occupa,onal  Therapists,  Die,,ans,  Naturopaths,  Acupuncturists,  Oriental  Medical  Prac,,oners,  Health  Coaches  and  lay  people  that  want  to  learn  how  to  live  a  healthier  life  is  also  part  of  Dr.  Brock's  mission.      He  enjoys  teaching  for  Apex  Energe,cs  as  well  as  providing    educa,on  and  support  to  facilitate  learning  for  mul,ple  groups  and  agencies.  This  includes  state  associa,on  mee,ngs  to  governmental  panels.  Dr.  Brock  is  also  enjoying  the  process  of  developing  in  part  his  own  func,onal  neurology  program  (Func,onal  Neurology  Seminars),  and  short  educa,onal  lectures  that  many  healthcare  and  medical  providers  can  learn  from  over  a  variety  of  topics.    Dr.  Brock  is  currently  a  clinical  lecturer  of  Pharmacology  at  the  Ins,tute  of  Healthcare  Professions,  clinical  neurology  lecturer  at  the  Academy  of  Osteopathic  Science  and  vice  president  of  the  Interna,onal  Associa,on  of  Func,onal  Neurology  and  Rehabilita,on  (IAFNR)  and  a  board  member  of  the  American  Academy  of  Integra,ve  Medicine  (AAIM).    He  was  recently  chosen  as  a  member  for  the  Council  of  Human  Func,on  and  has  been  an  expert  on  TAP  Integra,ve.          Dr.  Brock  received  the  most  outstanding  func,onal  neurology  teacher  of  the  year  from  the  ACA  council  of  Neurology  four  years  straight  and  two  ,mes  from  IAFNR  (Interna,onal  Associa,on  of  Func,onal  Neurology  and  Rehabilita,on).  This  year  Dr.  Brock  received  the  humanitarian  award  as  a  result  of  his  research  on  injured  Military  Veterans  and  PTSD  and  trauma,c  brain  injury  from  IAFNR.  Dr.  Brock  is  also  the  honorable  recipient  of  the  pres,gious  Living  Legacy  Award  from  Samford  Universi,es  Ida  Moffe\  School  Nursing  in  2015  and  he  was  recently  named  the  spotlight  student  of  his  doctoral  program  at  Duke  University.  He  holds  diplomate  status  in  Neurology,  Conven,onal  Medicine,  Nutri,on,  Integra,ve  Medicine  and  a  fellowship  from  the  Interna,onal  College  of  Chiropractors  as  well  as  the  American  Chiroprac,c  Neurology  Board.    Currently  Dr.  Brock  is  working  on  a  Doctorate  of  Nursing  Prac,ce  from  Duke  University  and  he  is  planning  on  immediately  upon  comple,on  of  the  program  at  Duke,  star,ng  a  conjoined  PhD  program  with  a  major  in  nursing  and  a  minor  in  behavioral  neuroscience.  Dr.  Brock’s  unique  blend  of  clinical  and  teaching  experience  along  with  a  background  in  medicine,  chiroprac,c,  neurology  and  nutri,on  has  created  a  very  unique  clinical  background  that  has  helped  him  treat  difficult  cases  and  offers  comprehensive  and  mul,-­‐-­‐-­‐perspec,ve  angles  on  educa,on  and  clinical  presenta,ons.  Ul,mately  you  can  typically  find  him  spending  ,me  with  his  new  wife  Tara  or  his  children,  Addy,  Zoey,  Kennedy  and  Conner.    They  all  love  to  travel,  read,  learn  and  live  life.    Dr.  Brock's  wife  is  a  fantas,c  English  teacher  at  Sunnyvale  High  School  and  Dr.  Brock  points  out  that  his  wife  Tara  is  the  best  and  most  grounded  thing  in  his  life,  along  with  his  kids,  co-­‐workers  and  friends.    

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Dr.  Da%s  Kharrazian    DC,  DHSc,  DACNB,  DABCN,  FACN,  CNS  

 Dr.  Da,s  Kharrazian  is  an  Associate  Clinical  Professor  at  Loma  Linda  University  School  of  Medicine.  He  has  contributed  significantly  to  the  field  of  func,onal  neurology  as  an  educator,  author,  and  researcher.  He  is  credited  with  integra,ng  the  func,onal  medicine  model  with  rehabilita,ve  neurology  to  evolve  the  specialty  into  a  more  comprehensive  treatment  model  of  brain  dysfunc,on.  He  developed  several  post-­‐graduate  programs,  protocols,  examina,on  forms,  and  ques,onnaire  forms  in  the  field  of  func,onal  neurology  that  are  being  been  used  by  thousands  of  health  care  professionals.  His  peers  at  the  first  Interna,onal  Associa,on  of  Func,onal  Neurology  and  Rehabilita,on  (IAFNR)  annual  mee,ng  recognized  him  with  the  “Clinical  Trailblazer”  Award  for  his  contribu,on  to  evolving  the  field  of  func,onal  neurology.  He  has  also  received  numerous  accolades  for  his  development  of  func,onal  medicine  programs.  He  is  the  author  of  the  best-­‐selling  book,  Why  Isn’t  my  Brain  Working?  This  book  has  received  hundreds  of  posi,ve  tes,monials  and  five  star  reviews  from  readers  throughout  the  world  and  is  being  translated  into  several  other  languages.  Many  reviewers  have  called  his  book  the  most  complete  and  innova,ve  compila,on  of  work  for  func,onal  neurology  nutri,onal  concepts.  Dr.  Kharrazian  teaches  neuroscience  and  human  brain  dissec,on  at  Bastyr  University  California  and  is  an  Adjunct  Professor  at  Na,onal  University  of  Health  Sciences,  where  he  is  developing  post-­‐graduate  programs  in  func,onal  neurology.  He  has  developed  a  30-­‐part  Neuroendocrine-­‐Immune  Series  and  a  Mastering  Brain  Chemistry  course  that  has  been  taught  to  thousands  of  health  care  professionals  throughout  the  country  and  approved  by  the  University  of  Bridgeport  Postgraduate  Department.  Dr.  Kharrazian  is  also  a  faculty  member  of  the  Ins,tute  for  Func,onal  Medicine  (IFM)  and  supports  program  development  in  func,onal  medicine,  func,onal  neurology,  neurological  physical  examina,on,  and  neurology  diagnos,c  applica,ons  to  brain-­‐based  disorders.  The  IFM  provides  medical  physicians  with  con,nuing  medical  educa,on  credits  required  for  physician  re-­‐licensure  and  is  accredited  by  the  Accredita,on  Council  for  Con,nuing  Medical  Educa,on.  Dr.  Kharrazian  is  a  Fellow  of  the  American  College  of  Nutri,on,  a  Diplomate  of  the  Board  of  Nutri,on  Specialists,  A  Diplomate  of  the  American  Chiroprac,c  Neurology  Board,  and  a  Diplomate  of  the  American  Clinical  Board  of  Nutri,on.  He  earned  a  Master  of  Science  degree  in  Human  Nutri,on  from  the  University  of  Bridgeport,  a  Doctor  of  Health  Science  from  Nova  Southeastern  University,  and  a  Doctor  of  Chiroprac,c  degree  from  Southern  California  University  of  Health  Sciences.  He  is  currently  comple,ng  his  Ph.D.  degree  at  Nova  Southeastern  University  with  doctoral  research  in  autoimmunity  and  immunology.  Dr.  Kharrazian  completed  a  one-­‐year  post-­‐doctorate  clinical  scholar  research  program  at  Harvard  Medical  School  and  is  an  associate  alumni  member  of  Harvard  University  and  Harvard  Medical  School.  He  has  published  several  scien,fic  papers  in  the  fields  of  nutri,on,  autoimmunity,  toxicology,  and  is  conduc,ng  research  in  autoimmune  molecular  mimicry  and  environmentally  induced  immune  reac,vity.  He  is  on  the  scien,fic  editorial  board  for  the  Journal  of  Func,onal  Neurology,  Rehabilita,on  and  Ergonomics  and  Alterna,ve  Medicine  Therapies  in  Health  and  Medicine.  He  is  also  is  a  requested  scien,fic  reviewer  for  several  scien,fic  journals,  including  the  Bri,sh  Journal  of  Medicine  and  Medical  Research.  In  addi,on  to  his  contribu,on  to  func,onal  neurology,  Dr.  Kharrazian  has  wri\en  numerous  papers,  manuals,  and  clinical  educa,onal  material  for  blood  chemistry  analysis,  hormone  and  endocrine  analysis,  complex  immunology  tes,ng,  gastrointes,nal  analysis,  and  func,onal  medicine.  He  has  trained  more  than  20  doctors  to  teach  his  model  of  func,onal  medicine  throughout  the  country.  Dr.  Kharrazian’s  approach  and  clinical  model  are  taught  at  more  than  200  loca,ons  each  year.  Dr.  Kharrazian  is  also  the  author  of  the  best-­‐selling  book,  Why  Do  I  S,ll  Have  Thyroid  Symptoms  When  My  Lab  Tests  are  Normal?  This  book  led  readers  to  develop  of  the  largest  Hashimoto’s  community  (Hashimoto’s  411)  on  Facebook,  and  the  development  of  a  non-­‐profit  pa,ent  advocacy  group  (Hashimoto’s  Awareness)  to  support  thyroid  pa,ents  from  around  the  world.  Dr.  Kharrazian  serves  on  the  Nutri,on  Leaders  Council.  This  is  an  en,ty  that  directly  contributes  to  the  Accredita,on  Council  for  Nutri,on  Professional  Educa,on,  ACNPE  (university  nutri,on  program  accredita,on),  Board  for  Nutri,on  Specialists,  BCNS,  (creden,aling  Body  and  Advocacy),  and  the  American  Nutri,on  Associa,on,  ANA  (educa,onal  and  advocacy  organiza,on).  Dr.  Kharrazian  is  a  consultant  to  the  nutri,on  industry  and  has  formulated  more  than  100  products,  which  are  used  by  health  care  professionals.  He  also  serves  as  a  consultant  to  Cyrex  Laboratory,  where  he  provides  expert  clinical  opinion  on  the  development  of  complex  immunology  profiles.  Dr.  Kharrazian  has  a  private  prac,ce  for  pa,ents  from  around  the  world  seeking  non-­‐pharmaceu,cal  alterna,ves  to  manage  chronic  condi,ons.  He  uses  diet,  nutri,on,  neurological  rehabilita,ve  exercises,  and  lifestyle  applica,ons  in  his  protocols.  His  prac,ce  has  a  two-­‐year  wai,ng  list  and  is  limited  to  pa,ents  suffering  from  chronic  condi,ons.  Most  of  Dr.  Kharrazian’s  pa,ents  are  referred  from  other  health  care  professionals  both  na,onally  and  interna,onally.  As  an  educator,  researcher,  and  clinician,  Dr.  Kharrazian  has  blended  his  scien,fic  research  with  clinical  experience  to  develop  effec,ve  concepts  and  applica,ons  for  complex  health  disorders,  which  have  been  used  by  thousands  of  health  care  professionals  and  pa,ents  around  the  world.  

5  

Func,onal  Neurology  Seminars  LP  ©  2016  

World Parkinson Congress

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Parkinsonian Gait Examples

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Nature Reviews Neurology 8, 329-339 (June 2012)  

BRAINA JOURNAL OF NEUROLOGY

Severe olfactory dysfunction is a prodromalsymptom of dementia associated withParkinson’s disease: a 3 year longitudinal studyToru Baba,1 Akio Kikuchi,1 Kazumi Hirayama,2,3 Yoshiyuki Nishio,2 Yoshiyuki Hosokai,2

Shigenori Kanno,2 Takafumi Hasegawa,1 Naoto Sugeno,1 Masatoshi Konno,1 Kyoko Suzuki,2,4

Shoki Takahashi,5 Hiroshi Fukuda,6 Masashi Aoki,1 Yasuto Itoyama,1,7 Etsuro Mori2 andAtsushi Takeda1

1 Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan2 Department of Behavioural Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan3 Department of Occupational Therapy, Yamagata Prefectural University of Health Sciences, Yamagata 990-2212, Japan4 Department of Clinical Neuroscience, Yamagata University, Graduate School of Medical Science, Yamagata 990-9585, Japan5 Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan6 Department of Nuclear Medicine and Radiology, Institute of Development, Ageing and Cancer, Tohoku University, Sendai 980-8575, Japan7 National Centre Hospital, Tokyo 187-8551, Japan

Correspondence to: Atsushi Takeda,Department of Neurology,Tohoku University Graduate School of Medicine,1-1 Seiryo-machi, Aoba-ku,Sendai 980-8574, JapanE-mail: atakeda@med.tohoku.ac.jp

Dementia is one of the most debilitating symptoms of Parkinson’s disease. A recent longitudinal study suggests that up to 80%

of patients with Parkinson’s disease will eventually develop dementia. Despite its clinical importance, the development of

dementia is still difficult to predict at early stages. We previously identified olfactory dysfunction as one of the most important

indicators of cortical hypometabolism in Parkinson’s disease. In this study, we investigated the possible associations between

olfactory dysfunction and the risk of developing dementia within a 3-year observation period. Forty-four patients with

Parkinson’s disease without dementia underwent the odour stick identification test for Japanese, memory and visuoperceptual

assessments, 18F-fluorodeoxyglucose positron emission tomography scans and magnetic resonance imaging scans at baseline

and 3 years later. A subgroup of patients with Parkinson’s disease who exhibited severe hyposmia at baseline showed more

pronounced cognitive decline at the follow-up survey. By the end of the study, 10 of 44 patients with Parkinson’s disease had

developed dementia, all of whom had severe hyposmia at baseline. The multivariate logistic analysis identified severe hyposmia

and visuoperceptual impairment as independent risk factors for subsequent dementia within 3 years. The patients with severe

hyposmia had an 18.7-fold increase in their risk of dementia for each 1 SD (2.8) decrease in the score of odour stick identi-

fication test for Japanese. We also found an association between severe hyposmia and a characteristic distribution of cerebral

metabolic decline, which was identical to that of dementia associated with Parkinson’s disease. Furthermore, volumetric mag-

netic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and the atrophy of focal brain

structures, including the amygdala and other limbic structures. Together, our findings suggest that brain regions related to

olfactory function are closely associated with cognitive decline and that severe hyposmia is a prominent clinical feature that

predicts the subsequent development of Parkinson’s disease dementia.

doi:10.1093/brain/awr321 Brain 2012: 135; 161–169 | 161

Received July 28, 2011. Revised September 25, 2011. Accepted September 28, 2011! The Author (2011). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.For Permissions, please email: journals.permissions@oup.com

by guest on May 1, 2016

http://brain.oxfordjournals.org/D

ownloaded from

BRAINA JOURNAL OF NEUROLOGY

Olfactory dysfunction, central cholinergic integrityand cognitive impairment in Parkinson’s diseaseNicolaas I. Bohnen,1,2,3 Martijn L. T. M. Muller,1 Vikas Kotagal,2 Robert A. Koeppe,1

Michael A. Kilbourn,1 Roger L. Albin2,3 and Kirk A. Frey1,2

1 Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI 48109, USA2 Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA3 Neurology Service and GRECC, VAAAHS, Ann Arbor, MI 48105, USA

Correspondence to: Nicolaas I. Bohnen,Functional Neuroimaging, Cognitive and Mobility Laboratory,Departments of Radiology and Neurology,University of Michigan, 24 Frank Lloyd Wright Drive,Box 362, Ann Arbor, MI, USAE-mail: nbohnen@umich.edu

Olfactory dysfunction is common in subjects with Parkinson’s disease. The pathophysiology of such dysfunction, however,

remains poorly understood. Neurodegeneration within central regions involved in odour perception may contribute to olfactory

dysfunction in Parkinson’s disease. Central cholinergic deficits occur in Parkinson’s disease and cholinergic neurons innervate

regions, such as the limbic archicortex, involved in odour perception. We investigated the relationship between performance on

an odour identification task and forebrain cholinergic denervation in Parkinson’s disease subjects without dementia. Fifty-eight

patients with Parkinson’s disease (mean Hoehn and Yahr stage 2.5! 0.5) without dementia (mean Mini-Mental State

Examination, 29.0! 1.4) underwent a clinical assessment, [11C]methyl-4-piperidinyl propionate acetylcholinesterase brain posi-

tron emission tomography and olfactory testing with the University of Pennsylvania Smell Identification Test. The diagnosis of

Parkinson’s disease was confirmed by [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 positron emission

tomography. We found that odour identification test scores correlated positively with acetylcholinesterase activity in the

hippocampal formation (r = 0.56, P50.0001), amygdala (r = 0.50, P50.0001) and neocortex (r = 0.46, P = 0.0003). Striatal mono-

aminergic activity correlated positively with odour identification scores (r = 0.30, P50.05). Multiple regression analysis includ-

ing limbic (hippocampal and amygdala) and neocortical acetylcholinesterase activity as well as striatal monoaminergic activity,

using odour identification scores as the dependent variable, demonstrated a significant regressor effect for limbic acetylcholin-

esterase activity (F = 10.1, P50.0001), borderline for striatal monoaminergic activity (F = 1.6, P = 0.13), but not significant for

cortical acetylcholinesterase activity (F = 0.3, P = 0.75). Odour identification scores correlated positively with scores on cognitive

measures of episodic verbal learning (r = 0.30, P50.05). These findings indicate that cholinergic denervation of the limbic

archicortex is a more robust determinant of hyposmia than nigrostriatal dopaminergic denervation in subjects with moderately

severe Parkinson’s disease. Greater deficits in odour identification may identify patients with Parkinson’s disease at risk for

clinically significant cognitive impairment.

Keywords: acetylcholinesterase; cognitive impairment; Parkinson’s disease; positron emission tomography; smell

Abbreviations: AChE = acetylcholinesterase; UPSIT = University of Pennsylvania Smell Identification Test; VMAT2 = vesicularmonoamine transporter type 2

doi:10.1093/brain/awq079 Brain 2010: 133; 1747–1754 | 1747

Received December 8, 2009. Revised March 3, 2010. Accepted March 5, 2010. Advance Access publication April 22, 2010! The Author(s) 2010. Published by Oxford University Press on behalf of Brain.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5),which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The University of Pennsylvania Smell Identification Test (UPSIT)

Peanut Butter Test for Alzheimer’s

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Quick smell test to help Identify Alzheimer’s disease

•  Star,ng  with  a  li\le  peanut  bu\er  at  the  bo\om  of  a  ruler,  measure  the  distance  from  the  nostril  where  pa,ents  were  first  able  to  detect  the  odor.    

•  Pa,ents  who  detected  the  odor  at  least  6  cm  worse  with  the  leP  nostril  than  with  the  right  were  also  diagnosed  with  Alzheimer’s.    

•  Pa,ents  diagnosed  with  other  types  of  demen,a  and  healthy  older  people  did  not  show  this  leP-­‐worse-­‐than-­‐right  nostril  difference.    

•  This  reliable,  noninvasive  test  may  help  detect  Alzheimer’s  early  because  evidence  suggests  the  smell  area  of  the  brain,  par,cularly  on  the  leP  side,  is  the  first  area  affected  

J  Neurol  Neurosurg  Psychiatry.  2002  May;72(5):560-­‐563.  Gluten  sensi%vity  as  a  neurological  illness.  

MRI of a patient with gluten ataxia showing rapid onset of cerebellar atrophy over a period of 15 months before the diagnosis of gluten ataxia

Gluten  ataxia    

•  “Gluten  ataxia…should  be  considered  in  the  differen,al  diagnosis  of  all  pa%ents  with  idiopathic  sporadic  ataxia.”  

•  “Early  diagnosis  and  treatment  with  a  gluten-­‐free  diet  can  improve  ataxia  and  prevent  its  progression.”  

Cerebellum.  2008;7(3):494-­‐498.  

Autoantibodies to glutamic acid decarboxylase in three patients with cerebellarataxia,

late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity.

•  “GAD-­‐Abs  should  be  sought  in  pa,ents  with  cerebellar  ataxia  who  have  late-­‐onset  IDDM  and  other  organ-­‐specific  autoimmune  manifesta,ons.”  

Neurology.  1997  Oct;49(4):1026-­‐30.  

Anti-thyroperoxidase antibodies from patients with Hashimoto's encephalopathy bind to cerebellar astrocytes.

•  “Normal  human  astrocytes  from  primary  cultures  also  reacted  with  an,-­‐TPO  mAb.”  

•  “Specific  astrocyte  binding  of  an,-­‐TPO  aAb  suggests  a  role  of  these  aAb  in  the  Hashimoto’s  encephalopathy  pathogenesis”  

J  Neuroimmunol.  2007  Dec;192(1-­‐2):13-­‐20.    

Funct Neurol Rehabil Ergon 2014;4(2-3) ISSN: 2156-941X © 2014 Nova Science Publishers, Inc.

Neuroendocrine-Immunology Mechanisms of Subtle Cerebellum Impairment

Datis Kharrazian∗ Basytr University California, San Diego, CA

Abstract Cerebellum degeneration and impairment may occur from both clinically obvious and subtle mechanisms.

Obvious mechanisms of cerebellum disease include acute onset found with trauma and vascular lesions, compressive signs found with tumor, infectious mechanisms associated with fever and abnormal immune serology, and genetic patterns that have distinct identifying clinical features. Subtle neuroendocrine-immune mechanisms that can impair and degenerate the cerebellum include gluten specific cross-reactivity, Hashimoto’s encephalopathy, hypothyroidism, dysglycemia, subtle cerebellum autoimmunity, paraneoplastic cerebellum syndrome, or toxicological insults to cerebellum granulocytes and Purkinje cells. This paper reviews subtle neuroendocrine-immune mechanisms that insult the cerebellum.

Keywords: cerebellum, gluten specific cerebellar ataxia, and Hashimoto's encephalopathy,

Introduction Neurology professionals find various stages of cerebellum impairment in their practices. Early

degenerative disease findings are identical to progressed findings and are differentiated by a graded scale of mild, moderate, and severe. Clinical findings of cerebellum disease include wide-stance and scissor gait, hypotonia, pendulum reflexes, ataxia, truncal titubation, poor posture, vertigo, dysdiadochokinesia, ocular and limb dysmetria, nystagmus, saccadic intrusion into smooth pursuit, hypometric and hypermetric saccades, abnormal optikinetic reflexes, inability to cancel the vestibule-ocular reflexes, square-wave jerks, scanning dysarthria and tremor of voice, kinetic and termination tremors, autonomic dystonia, and cognitive affective syndromes. [1]

Various neuroendocrine-immune mechanisms may promote degenerative changes in the cerebellum. They include metabolic, vascular, toxic, infectious, traumatic, carcinogenic, developmental, inflammatory, and genetic mechanisms. In addition to evaluating subjective and objective findings when looking at cerebellum impairment, it’s also important to identify various mechanisms of cerebellum disease. This paper focuses on identifying early mechanisms of cerebellum disease, excluding obvious mechanisms such as traumatic brain injury, tumors, stroke, infections, and genetic disorders. These more obvious mechanisms have clear clinical presentation either from their

∗ Correspondence: Dr. Datis Kharrazian, 1001 Canvasback Court, Carlsbad CA, 92011 Email: datis56@gmail.com

Clinical Pearl

•  Remember,  pa\erns  of  neurodevelopmental  delays  that  may  have  been  improved  into  adulthood  are  usually  the  first  regions  to  show  pa\erns  of  neurodegenera,on  into  late  adulthood.