ahuja gr young onset dementia
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Brian S. Appleby, M.D.Associate Professor
Department of Neurology
Young-Onset Dementia An Overview
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Objectives
• Describe epidemiological characteristics of young-onset dementia (YOD)
• Discuss the differential diagnoses and evaluation of YOD
• Understand unique patient and caregiver challenges in YOD
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Definition
Cognitive and functional impairment in individuals <65 years of age
Further classification:Early-onset: <65 years of ageYoung-onset: <45 years of age
Kelley BJ, Arch Neurol 2008
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Cognitive Symptoms
Memory Clinic, <60 years of age:-55%, no cognitive deficits-17%, selective cognitive deficits-15%, demented -13%, not classified
Vraamark Elberling T, Neurology 2002
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Patients with Dementia
Vraamark Elberling T, Neurology 2002
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No Cognitive Deficits
Vraamark Elberling T, Neurology 2002
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EpidemiologyAge Range Prevalence rate (per 100,000)
Male Female Total30-64 62.6 45.5 54.045-64 119.8 76.5 98.1
Harvey RJ, J Neurosurg Neurol Psychiatry 2003Garre-Olmo J, Neurology 2010
Age Range Prevalence rate (per 100,000)Male Female Total
30-64 13.0 13.9 13.4
50-64 - - 18
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Demographics of YOD
Baldwin, 1994 Harvey, 2003 Fujihara, 2004 Papageorgiou, 2009 Garre-Olmo, 2010
N 43 185 141 114 144Mean Age 59 58 53 59 58.1Male 28 (65%) 107(58%) 86 (61%) 55 (48%) 73 (50.7%)
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Papageorgiou S, Alzheimer Dis Assoc Disord 2009
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Fujihara S, Arq Neuropsiquiatr 2004
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Kelley BJ, Arch Neurol 2008
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Kelley BJ, Dement Geriatr Cogn Disord 2009
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Dementia Types
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Alzheimer’s disease• Most prevalent YOD• Presents differently in younger patients
– 33% have non-memory symptoms– Visuospatial impairment– Apraxia
• Pathogenetic etiology (<1%)– Presenilins 1&2– Amyloid precursor protein– APOE4 effect
Tang-Wai DF, Neurology 2004Koedam EL, J Alzheimers Dis 2010
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Frontotemporal Lobar Degeneration
• Frontotemporal Dementia
• Primary progressive aphasia
• Semantic dementia
• Progressive non-fluent aphasia
• Logopenic aphasia• Progressive
supranuclear palsy• Corticobasal
degeneration
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Creutzfeldt-Jakob disease(CJD)
Genetic CJDFatal familial insomniaGerstmann-Sträussler-Scheinker
KuruIatrogenic CJDVariant CJD
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YOD Challenges• Diagnosis• Occupational • Financial• Social• Family-spouse and children, genetics• Behavioral issues• Better overall health and mobility• Disease specific-FTD, fAD, CJD
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Caregiver Burden
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ZBI=Zarit Burden Interview From: Johns Hopkins FTD/YOD Clinic
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Delany N, Int J Ger Psych 1995Sperlinger D, Int J Ger Psych 1994
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Atypical Presentation
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Ebner L, Alzheimer’s and Dementia 2010
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Frontotemporal dementiaSchizophrenia-like psychosis
Velakoulis D, Br J Psychiatry 2009
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Late Onset C9ORF72 Carriers
• Mostly FTD phenotype• Differences:
– initial cognitive impairment (memory)– Late onset psychosis
Galimberti D, Biological Psychiatry 2013
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Appleby BS, J Clin Neurosci Neuropsychiatry 2007
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Delayed Presentation
From onset to initial evaluation3.9 years (Garre-Olmo J, Neurology 2010)
3 years (Fujihara S, Arq Neuropsiquiatr 2004)
3 years (Papageorgiou SG, Alzheimer Dis Assoc Disord 2009)
2 years (Kelley BJ, Dement Geriatr Cogn Disord 2009)
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Appleby BS, Arch Neurol 2009
Sporadic CJD Time to Presentation(Log-rank test, χ2= 18.35, P = .003)
Mean age=59.7
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Referral Patterns
Newens AJ, Br J Gen Pract 1994
Neurologist-> 63%
Psychiatrist-> 27%
Other physician->9%
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Work-up Patterns
Newens AJ, Br J Gen Pract 1994
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DiagnosisHistory
• Course of illness• Pattern of cognitive deficit• Family history• Other neurological signs/symptoms• Other systemic illness• Social/Drug history
Ridha B & Josephs KA. The Neurologist 2006
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Preliminary work-up
• CBC• CMP• TSH• Vitamin B12, D3, folate• RPR• ESR• HIV
• Brain MRI w/wo
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Expanded work-up
• Antibody screen• Ceruloplasmin• Iron studies• Heavy metal screen• SPEP/UPEP• Homocysteine• NH3• Genetic testing
• Brain PET scan• EEG• LP• Whole body CT
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Case presentations
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Case #1• 60 y.o. WF with h/o rheumatic fever, GERD,
vit D def, osteopenia, and liver/brain hemangiomas
• 1 yr h/o progressive strabismus with diplopia (repaired with return 1 mo later), parkinsonism, dysarthria, and short-term amnesia, fatigue, anxiety, panic attacks
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Exam Speech: hypophonic, sparse, dysarthricThought Process: bradyphrenicAffect: stable, flat without brighteningMMSE: 7/30UPDRS II: 43Neuro: vertical gaze impairment, choppy saccades, hypomimia, axial rigidity
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Case #2• 58 y.o. AAM attorney with h/o dyslexia with
a 2 yr h/o cognitive decline and personality change
• Distracted, poor concentration, low mood, fatigued
• Only reads comic books and watches cartoons, often the same ones repeatedly
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Exam
General: Asked to leave room several times to walk around. Buccal stereotypies (i.e., blowing)Speech: Sparse, poverty of contentAffect: Flat, no brighteningMMSE: 19/30Brain MRI: Mild generalized atrophy
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Further Work-up
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Case 3
• 61 y.o. MWF, R-handed• Insidious onset, gradual progression x 1 year• Initial sx’s of effortful speech, skips nouns,
semantic paraphrasic errors• Later developed concentration difficulties,
fatigue, easily overwhelmed
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Exam
• MMSE: 25/30 (-4 calc, -1 read/obey)• 3MS: 83/100• Mild L hand resting tremor• Glabellar sign
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Diagnostics
• EEG: diffuse slowing• CSF: RBC=32, WBC=2, pro=25, glu=57, 14-3-3
neg, tau=354• Body FDG-PET: B thyroid lobe activity• Two brain MRI w/ cortical hyperintensity on
DWI, no ADC changes, and no changes in btwn studies
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Case #4
• 50 y.o. female from Spain with 4 yr h/o gradual executive dysfxn, short-term amnesia, progressive non-fluent aphasia, parkinsonism, and myoclonus
• Paces frequently, apathetic, crying when frustrated, seen responding to internal stimuli, and sometimes thinks others are stealing from her
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ExamGait: slow, shuffling, leans to leftSpeech: Effortful, paraphrasic errorsMMSE: 5/303MS: 17/100Clock: 1/5UPDRS II: 44• Myoclonus with speech and action• Left-sided neglect, finger agnosia
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Exam
Pentagons Clock
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Case #5
• 74 y.o. MWF with no past neuropsych history• Two family members had ALS• Presents with couple year history of profound
anxiety and compulsion to call her friends• Worried that if she does not call them,
something bad will happen to her family
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Exam and Work-Up
• Extremely tense and anxious, emotionally labile• Accuses husband of mistreating her• Cognitive screening was most indicative of
impairment in delayed recall• Elevated anti-thryoglobulin/thyroperoxidase Ab,
no improvement on IV steroids• Genetic testing demonstrated C9ORF72
mutation
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University Hospitals Case Medical Center Studies
• SNIFF (intranasal insulin for MCI and AD)• A4 (treatment in asymptomatic AD)• Isotretinoin (AD)• ADNI (Neuroimaging in AD)• TauRx (frontotemporal dementia)• FDA diagnostic study for sCJD (sCJD, AD, FTD)• FDG-PET neuroimaging in prion disease• Art therapy in prion disease• Determinants of initial diagnosis of prion disease• Cataracts in dementia