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Young-Onset Dementias Forensic Implications AAPL 2009 Presented by: Ryan C.W. Hall, M.D. and Brian S. Appleby, M.D.
Disclosures <ul><li>Co-Investigator of a multi-center trial of memantine for the treatment of frontotemporal dementia (For...
Objectives <ul><li>Demonstrate the differential diagnosis for young-onset dementias </li></ul><ul><li>Describe the neurops...
Dementia <ul><li>Cognitive impairment </li></ul><ul><li>Intact consciousness </li></ul><ul><li>Functional impairment </li>...
Cognition Short-term memory Language Praxis Visuospatial skills Executive Functioning Emotion and personality
Definition <ul><li>Cognitive and functional impairment in individuals <65 years of age </li></ul><ul><li>Further classific...
Cognitive Symptoms <ul><li>Memory Clinic, <60 years of age: </li></ul><ul><li>-55%, no cognitive deficits </li></ul><ul><l...
No Cognitive Deficits
Epidemiology (45-64 years of age) <ul><li>Incidence: 11.5 per 100,000 individuals </li></ul><ul><li>Prevalence: 98.1 per 1...
Epidemiology Harvey RJ,  et al.  J Neurosurg Neurol Psychiatry , 2003 Age Range Prevalence rate (per 100,000) Male Female ...
October 30, 2009 Causes of young-onset dementia Alzheimer disease Cerebrovascular disease Frontotemporal dementias Metabol...
Fujihara S,  et al.  Arq Neuropsiquiatr , 2004
Papageorgiou SG, et al ., Alzheimer Dis Assoc Disord, 2009 AD FTD
<45 years of age Kelley BJ, et al . Arch Neurol, 2008
Challenges <ul><li>Diagnosis </li></ul><ul><li>Occupational  </li></ul><ul><li>Financial </li></ul><ul><li>Social </li></u...
ZBI=Zarit Burden Interview Johns Hopkins FTD/YOD Clinic
Delany N,  et al.  Int J Ger Psych , 1995 Sperlinger D,  et al. Int J Ger Psych , 1994
Appleby BS,  et al.  [In Press]
Velakoulis D, et al . BJP 2009 The solid curve shows the percentage of patients with frontotemporal dementia presenting wi...
Appleby BS, et al . J Neuropsychiatry Clin Neurosci, 2007
Delayed Presentation <ul><li>From onset to initial evaluation </li></ul><ul><li>3 years  (Fujihara S,  et al.  Arq Neurops...
Creutzfeldt-Jakob disease Appleby, B. S. et al. Arch Neurol 2009;66:208-215. (Log-rank test,  χ 2 = 18.35,  P  = 0.003)   ...
Referral Patterns Newens AJ,  et al.  Br J Gen Pract , 1994 Neurologist-> 63% Psychiatrist-> 27% Other physician->9%
Work-up Patterns
Why Psychiatrists? <ul><li>High prevalence of  behavioral disorders </li></ul><ul><li>Frequently taking psychotropic meds ...
We are already seeing them! Newens AJ,  et al.  Br J Gen Pract , 1994
Diagnosis History <ul><li>Course of illness </li></ul><ul><li>Pattern of cognitive deficit </li></ul><ul><li>Family histor...
Preliminary work-up <ul><li>CBC </li></ul><ul><li>Coagulation studies </li></ul><ul><li>CMP </li></ul><ul><li>TFT’s </li><...
Expanded work-up <ul><li>Antibody screen </li></ul><ul><li>Ceruloplasmin </li></ul><ul><li>Iron studies </li></ul><ul><li>...
Alzheimer’s disease (AD) <ul><li>Most prevalent dementia  </li></ul><ul><li>Presents differently in younger patients </li>...
Case <ul><li>57-year-old man with AD </li></ul><ul><li>Initial symptoms were visuospatial impairment and acalculia </li></...
Frontotemporal Lobar Degeneration Frontotemporal Dementia Progressive Non-fluent Aphasia Semantic Dementia Neary D, et al....
FTD   Core Diagnostic Features <ul><ul><li>Insidious onset, gradual progression </li></ul></ul><ul><ul><li>Early decline i...
FTD Supportive diagnostic features <ul><li>Behavioral disorder </li></ul><ul><li>Speech and language disorder </li></ul><u...
@ Primitive reflexes and drives Rational thought, inhibition Illustration from Wider Than The Sky: The Phenomenal Gift Of ...
Phineas Gage
Case <ul><li>55-year-old gentleman with FTD </li></ul><ul><li>First presentation at airplane security </li></ul><ul><li>Mu...
Case <ul><li>59-year-old women with cortical basal degeneration </li></ul><ul><li>Expressive aphasia and acalculia </li></...
Traumatic Brain Injury <ul><li>Cognitive and neuropsychiatric effects </li></ul><ul><li>Coup/contre-coup preferentially af...
N Appleby BS,  et al. Dement Geriatr Cogn Disord , 2008
Creutzfeldt-Jakob disease <ul><li>Prion disease </li></ul><ul><li>Rapidly progressive dementia </li></ul><ul><li>Symptoms ...
Creutzfeldt-Jakob disease (CJD)
Definite CJD <ul><li>Histology </li></ul><ul><li>Immunohistochemistry </li></ul>
Probable CJD <ul><li>Two symptoms: </li></ul><ul><ul><li>Cerebellar and/or visual impairment </li></ul></ul><ul><ul><li>My...
EEG Period sharp wave complexes
Brain MRI DWI/FLAIR  Cortical ribbon Basal ganglia
Case #4 <ul><li>57-year-old man with sCJD </li></ul><ul><li>Social stressors </li></ul><ul><ul><li>Lack of support </li></...
King S.  Lancet , 2008
Huntington’s disease <ul><li>Trinucleotide repeat (CAG) disorder </li></ul><ul><li>Genetic anticipation </li></ul><ul><li>...
Case <ul><li>40-year-old male with moderate dementia and psychosis from HD attacks a medical student during an examination...
CASE PRESENTATIONS
Case #1 <ul><li>64 y.o. Caucasian female </li></ul><ul><li>Problems remembering dates and conversations, would repeat self...
Brain MRI
Case #2 <ul><li>51 y.o. Caucasian male </li></ul><ul><li>Trouble focusing, prioritizing, organizing </li></ul><ul><li>Incr...
Brain MRI
Case #3 <ul><li>39 y.o. Jordanian male </li></ul><ul><li>Painful paresthesias of his feet (Aug) </li></ul><ul><li>Depressi...
Brain MRI
Case #4 <ul><li>41 y.o. Caucasian female </li></ul><ul><li>Following birth of child in her 30’s became anergic, depressed,...
Head CT
Case #5 <ul><li>43 y.o. Caucasian male </li></ul><ul><li>History of alcohol, benzo, opioid abuse </li></ul><ul><li>Found i...
MRI , 8 months after inhalation
MRI , 16 months after acute phase
Thank you <ul><li>Johns Hopkins FTD/YOD Clinic: </li></ul><ul><li>Chiadi Onyike </li></ul><ul><li>Mary Anne Wylie </li></u...
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Research on Young-Onset Dementia and Its Implications for Criminal and Civil Forensic Cases

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Overview of young-onset dementias with research update and discussion on forensic implications

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  • Transcript of "Research on Young-Onset Dementia and Its Implications for Criminal and Civil Forensic Cases"

    1. 1. Young-Onset Dementias Forensic Implications AAPL 2009 Presented by: Ryan C.W. Hall, M.D. and Brian S. Appleby, M.D.
    2. 2. Disclosures <ul><li>Co-Investigator of a multi-center trial of memantine for the treatment of frontotemporal dementia (Forest Laboratories) </li></ul><ul><li>Honoraria from the CJD Foundation </li></ul>
    3. 3. Objectives <ul><li>Demonstrate the differential diagnosis for young-onset dementias </li></ul><ul><li>Describe the neuropsychiatric complications of young-onset dementias </li></ul><ul><li>Understand the management and legal complications of young-onset dementias </li></ul>
    4. 4. Dementia <ul><li>Cognitive impairment </li></ul><ul><li>Intact consciousness </li></ul><ul><li>Functional impairment </li></ul>
    5. 5. Cognition Short-term memory Language Praxis Visuospatial skills Executive Functioning Emotion and personality
    6. 6. Definition <ul><li>Cognitive and functional impairment in individuals <65 years of age </li></ul><ul><li>Further classification : </li></ul><ul><li>Early-onset: <65 years of age </li></ul><ul><li>Young-onset: <45 years of age </li></ul>Kelley BJ, et al. Arch Neurol , 2008
    7. 7. Cognitive Symptoms <ul><li>Memory Clinic, <60 years of age: </li></ul><ul><li>-55%, no cognitive deficits </li></ul><ul><li>-13%, mild cognitive complaints </li></ul><ul><li>-17%, selective cognitive deficits </li></ul><ul><li>-15%, demented </li></ul>Vraamark Elberling T, et al. Neurology , 2002
    8. 8. No Cognitive Deficits
    9. 9. Epidemiology (45-64 years of age) <ul><li>Incidence: 11.5 per 100,000 individuals </li></ul><ul><li>Prevalence: 98.1 per 100,000 individuals </li></ul>Mercy L, et al . Neurology, 2009 Harvey RJ, et al . J Neurol Neurosurg Psychiatry 2003
    10. 10. Epidemiology Harvey RJ, et al. J Neurosurg Neurol Psychiatry , 2003 Age Range Prevalence rate (per 100,000) Male Female Total 30-64 62.6 45.5 54.0 45-64 119.8 76.5 98.1
    11. 11. October 30, 2009 Causes of young-onset dementia Alzheimer disease Cerebrovascular disease Frontotemporal dementias Metabolic disorders Traumatic brain injury HIV/AIDS dementia Alcohol-related dementia Huntington disease Prion dementias Multiple sclerosis Autoimmune illnesses
    12. 12. Fujihara S, et al. Arq Neuropsiquiatr , 2004
    13. 13. Papageorgiou SG, et al ., Alzheimer Dis Assoc Disord, 2009 AD FTD
    14. 14. <45 years of age Kelley BJ, et al . Arch Neurol, 2008
    15. 15. Challenges <ul><li>Diagnosis </li></ul><ul><li>Occupational </li></ul><ul><li>Financial </li></ul><ul><li>Social </li></ul><ul><li>Family-spouse and children </li></ul><ul><li>Behavioral issues </li></ul><ul><li>Better overall health and mobility </li></ul><ul><li>Disease specific-FTD, fAD, CJD </li></ul>
    16. 16. ZBI=Zarit Burden Interview Johns Hopkins FTD/YOD Clinic
    17. 17. Delany N, et al. Int J Ger Psych , 1995 Sperlinger D, et al. Int J Ger Psych , 1994
    18. 18. Appleby BS, et al. [In Press]
    19. 19. Velakoulis D, et al . BJP 2009 The solid curve shows the percentage of patients with frontotemporal dementia presenting with schizophrenia-like psychosis; the dashed curve shows the cumulative number of patients with frontotemporal dementia
    20. 20. Appleby BS, et al . J Neuropsychiatry Clin Neurosci, 2007
    21. 21. Delayed Presentation <ul><li>From onset to initial evaluation </li></ul><ul><li>3 years (Fujihara S, et al. Arq Neuropsiquiatr , 2004) </li></ul><ul><li>3 years (Papageorgiou SG, et al. Alzheimer Dis Assoc Disord , 2009) </li></ul><ul><li>2 years (Kelley BJ, et al. Dement Geriatr Cogn Disord , 2009) </li></ul>
    22. 22. Creutzfeldt-Jakob disease Appleby, B. S. et al. Arch Neurol 2009;66:208-215. (Log-rank test, χ 2 = 18.35, P  = 0.003) Mean age=59.7
    23. 23. Referral Patterns Newens AJ, et al. Br J Gen Pract , 1994 Neurologist-> 63% Psychiatrist-> 27% Other physician->9%
    24. 24. Work-up Patterns
    25. 25. Why Psychiatrists? <ul><li>High prevalence of behavioral disorders </li></ul><ul><li>Frequently taking psychotropic meds </li></ul><ul><ul><li>41% on neuroleptics </li></ul></ul><ul><li>High degree of strain and psychiatric morbidity in caregivers </li></ul><ul><li>Need for education </li></ul>Baldwin RC. Psychiatr Bull , 1994 Kelley BJ, et al. Dement Geriatr Cogn Disord , 2009 Delany N & Rosenvinge H. Int J Ger Psychiatry , 1995
    26. 26. We are already seeing them! Newens AJ, et al. Br J Gen Pract , 1994
    27. 27. Diagnosis History <ul><li>Course of illness </li></ul><ul><li>Pattern of cognitive deficit </li></ul><ul><li>Family history </li></ul><ul><li>Other neurological signs/symptoms </li></ul><ul><li>Other systemic illness </li></ul><ul><li>Social/Drug history </li></ul>Ridha B & Josephs KA. The Neurologist , 2006
    28. 28. Preliminary work-up <ul><li>CBC </li></ul><ul><li>Coagulation studies </li></ul><ul><li>CMP </li></ul><ul><li>TFT’s </li></ul><ul><li>Vitamin B12 & folate </li></ul><ul><li>Fasting lipid panel </li></ul><ul><li>RPR </li></ul><ul><li>ESR & CRP </li></ul><ul><li>Urine toxicology </li></ul><ul><li>Brain MRI </li></ul><ul><li>Neuropsych testing </li></ul>
    29. 29. Expanded work-up <ul><li>Antibody screen </li></ul><ul><li>Ceruloplasmin </li></ul><ul><li>Iron studies </li></ul><ul><li>Heavy metal screen </li></ul><ul><li>SPEP/UPEP </li></ul><ul><li>Homocysteine </li></ul><ul><li>NH4 </li></ul><ul><li>Genetic testing </li></ul><ul><li>Brain PET scan </li></ul><ul><li>EEG </li></ul><ul><li>LP </li></ul><ul><li>Whole body PET </li></ul>
    30. 30. Alzheimer’s disease (AD) <ul><li>Most prevalent dementia </li></ul><ul><li>Presents differently in younger patients </li></ul><ul><ul><li>Posterior cortical atrophy </li></ul></ul><ul><ul><li>Driving concerns </li></ul></ul><ul><li>Familial illness (<1%) </li></ul><ul><ul><li>Pre-senilin-1&2 </li></ul></ul><ul><ul><li>Amyloid precursor protein </li></ul></ul>Tang-Wai DF, et al. Neurology, 2004
    31. 31. Case <ul><li>57-year-old man with AD </li></ul><ul><li>Initial symptoms were visuospatial impairment and acalculia </li></ul><ul><li>Police contact for suspicions of driving while intoxicated </li></ul>
    32. 32. Frontotemporal Lobar Degeneration Frontotemporal Dementia Progressive Non-fluent Aphasia Semantic Dementia Neary D, et al. Neurology, 1998
    33. 33. FTD Core Diagnostic Features <ul><ul><li>Insidious onset, gradual progression </li></ul></ul><ul><ul><li>Early decline in social interpersonal conduct </li></ul></ul><ul><ul><li>Early impairment in regulation of personal conduct </li></ul></ul><ul><ul><li>Early emotional blunting </li></ul></ul><ul><ul><li>Early loss of insight </li></ul></ul>Neary D, et al. Neurology, 1998
    34. 34. FTD Supportive diagnostic features <ul><li>Behavioral disorder </li></ul><ul><li>Speech and language disorder </li></ul><ul><li>Physical symptoms </li></ul><ul><li>Investigational findings </li></ul><ul><ul><li>Neuropsychological testing </li></ul></ul><ul><ul><li>EEG </li></ul></ul><ul><ul><li>Brain imaging </li></ul></ul>Neary D, et al. Neurology, 1998
    35. 35. @ Primitive reflexes and drives Rational thought, inhibition Illustration from Wider Than The Sky: The Phenomenal Gift Of Consciousness by Gerald Edelman
    36. 36. Phineas Gage
    37. 37. Case <ul><li>55-year-old gentleman with FTD </li></ul><ul><li>First presentation at airplane security </li></ul><ul><li>Multiple family stressors </li></ul><ul><ul><li>Social </li></ul></ul><ul><ul><li>Occupational </li></ul></ul><ul><ul><li>Financial </li></ul></ul><ul><li>Spouse displays positive coping skills in advocacy </li></ul><ul><li>Solution : Travel letters </li></ul>
    38. 38. Case <ul><li>59-year-old women with cortical basal degeneration </li></ul><ul><li>Expressive aphasia and acalculia </li></ul><ul><li>Hands blank checks to clerks </li></ul><ul><li>Young children, ages 9 and 14 </li></ul><ul><li>Solution: Pre-paid credit/debit cards and online video communication </li></ul>
    39. 39. Traumatic Brain Injury <ul><li>Cognitive and neuropsychiatric effects </li></ul><ul><li>Coup/contre-coup preferentially affect frontal lobe nerve fibers </li></ul><ul><li>Often associated with alcohol use </li></ul><ul><li>Chicken/Egg scenario </li></ul>
    40. 40. N Appleby BS, et al. Dement Geriatr Cogn Disord , 2008
    41. 41. Creutzfeldt-Jakob disease <ul><li>Prion disease </li></ul><ul><li>Rapidly progressive dementia </li></ul><ul><li>Symptoms </li></ul><ul><ul><li>Dementia </li></ul></ul><ul><ul><li>Cerebellar impairment </li></ul></ul><ul><ul><li>Vision impairment </li></ul></ul><ul><ul><li>Pyramidal/Extrapyramidal symptoms </li></ul></ul><ul><li>Mean age of onset=62 </li></ul><ul><li>Mean survival time=4-6 months </li></ul>
    42. 42. Creutzfeldt-Jakob disease (CJD)
    43. 43. Definite CJD <ul><li>Histology </li></ul><ul><li>Immunohistochemistry </li></ul>
    44. 44. Probable CJD <ul><li>Two symptoms: </li></ul><ul><ul><li>Cerebellar and/or visual impairment </li></ul></ul><ul><ul><li>Myoclonus </li></ul></ul><ul><ul><li>Akinetic mutism </li></ul></ul><ul><ul><li>Pyramidal and/or Extrapyramidal symptoms </li></ul></ul><ul><li>Diagnostic Investigations </li></ul><ul><ul><li>Electroencephalogram (EEG) </li></ul></ul><ul><ul><li>Cerebrospinal 14-3-3 protein </li></ul></ul><ul><ul><li>Brain MRI </li></ul></ul>
    45. 45. EEG Period sharp wave complexes
    46. 46. Brain MRI DWI/FLAIR Cortical ribbon Basal ganglia
    47. 47. Case #4 <ul><li>57-year-old man with sCJD </li></ul><ul><li>Social stressors </li></ul><ul><ul><li>Lack of support </li></ul></ul><ul><ul><li>Curiosity </li></ul></ul><ul><ul><li>Social construction (e.g. mad-cow disease) </li></ul></ul><ul><li>Solution : Family gives vague explanation (e.g. neurodegenerative illness) </li></ul>
    48. 48. King S. Lancet , 2008
    49. 49. Huntington’s disease <ul><li>Trinucleotide repeat (CAG) disorder </li></ul><ul><li>Genetic anticipation </li></ul><ul><li>Atrophy of the caudate nucleus </li></ul><ul><li>Movement (e.g. chorea), cognitive, and psychiatric symptoms </li></ul><ul><li>Increased risk of suicide </li></ul>
    50. 50. Case <ul><li>40-year-old male with moderate dementia and psychosis from HD attacks a medical student during an examination. </li></ul><ul><li>Risk assessment </li></ul><ul><li>Consent for treatment </li></ul>
    51. 51. CASE PRESENTATIONS
    52. 52. Case #1 <ul><li>64 y.o. Caucasian female </li></ul><ul><li>Problems remembering dates and conversations, would repeat self </li></ul><ul><li>Gradual progression with some daily fluctuations </li></ul><ul><li>↑ irritability, ↑ fatigue, ↓ functioning </li></ul><ul><li>Social withdrawal, suspicious at times </li></ul>
    53. 53. Brain MRI
    54. 54. Case #2 <ul><li>51 y.o. Caucasian male </li></ul><ul><li>Trouble focusing, prioritizing, organizing </li></ul><ul><li>Increase frequency and severity of angry outbursts </li></ul><ul><li>Loss of empathy </li></ul><ul><li>Rigid and resistant to change </li></ul><ul><li>Mini-mental state exam=30/30 </li></ul>
    55. 55. Brain MRI
    56. 56. Case #3 <ul><li>39 y.o. Jordanian male </li></ul><ul><li>Painful paresthesias of his feet (Aug) </li></ul><ul><li>Depression (Sept) </li></ul><ul><li>Forgetful (Nov) </li></ul><ul><li>Inability to dress self (Jan) </li></ul><ul><li>Worsening gait, incontinence, myoclonus (Feb) </li></ul>
    57. 57. Brain MRI
    58. 58. Case #4 <ul><li>41 y.o. Caucasian female </li></ul><ul><li>Following birth of child in her 30’s became anergic, depressed, and distractable </li></ul><ul><li>Progressed to impulsivity and more distractability (12 car accidents/5 yrs) </li></ul><ul><li>Periods of exhilaration and irritability with poor sleep </li></ul>
    59. 59. Head CT
    60. 60. Case #5 <ul><li>43 y.o. Caucasian male </li></ul><ul><li>History of alcohol, benzo, opioid abuse </li></ul><ul><li>Found in respiratory distress, obtunded with pinpoint pupils </li></ul><ul><li>Developed depression, apathy, disinhibition, MMSE=20/30 </li></ul>
    61. 61. MRI , 8 months after inhalation
    62. 62. MRI , 16 months after acute phase
    63. 63. Thank you <ul><li>Johns Hopkins FTD/YOD Clinic: </li></ul><ul><li>Chiadi Onyike </li></ul><ul><li>Mary Anne Wylie </li></ul><ul><li>Rebecca Rye </li></ul><ul><li>Kate Hicks </li></ul><ul><li>Peter Rabins </li></ul><ul><li>Kostas Lyketsos </li></ul>
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