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Young-Onset Dementia (YOD) — Viva Crisp Notes

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DEFINITION

The boundary is not universal — some authorities use <65 for "young-onset." Know both and state what definition you are using.

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EPIDEMIOLOGY

• Prevalence ≈ 67–81/100,000 persons aged 45–64
• Represents ~5–9% of all dementia cases
• Often delayed diagnosis (mean delay 4–5 years) due to atypical presentations and low clinical suspicion

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CAUSES — FLOWCHART BY AGE

DEMENTIA ONSET
      │
      ├─── Age < 45 yrs (Kelley 2008, Mayo Clinic)
      │         Most common:
      │         1. Frontotemporal dementia (FTD)
      │         2. Huntington disease
      │         3. Multiple sclerosis
      │         4. Autoimmune/inflammatory encephalopathy
      │         5. Neuropsychiatric lupus
      │         6. Mitochondrial disease
      │         7. Lysosomal storage disease
      │         8. Prion disease (CJD)
      │         9. CNS vasculitis
      │
      └─── Age 30–65 yrs (Harvey 2003)
                Most common:
                1. Alzheimer dementia (most common >45)
                2. Vascular dementia
                3. Frontotemporal dementia
                4. Alcohol-related dementia
                5. Dementia with Lewy bodies (DLB)
                6. Huntington disease
                7. Multiple sclerosis
                8. Down syndrome dementia
                9. CBD / prion disease / Parkinson dementia

Mayo Clinic overall breakdown: Neurodegenerative 31.1% → Autoimmune/Inflammatory 21.3% → Metabolic 10.6% → Unknown 18.7%

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BROAD AETIOLOGICAL FRAMEWORK

YOD CAUSES
├── NEURODEGENERATIVE
│   ├── Alzheimer disease (dominant if >45)
│   ├── Frontotemporal dementia (dominant if <45)
│   ├── Dementia with Lewy bodies
│   ├── Corticobasal degeneration (CBD)
│   └── Huntington disease (CAG repeat ↑)
│
├── VASCULAR
│   ├── Multi-infarct dementia
│   ├── Binswanger disease (subcortical)
│   └── CADASIL (Notch3 mutation — classic YOD cause)
│
├── AUTOIMMUNE / INFLAMMATORY
│   ├── Autoimmune encephalitis (anti-NMDAR, VGKC, LGI1)
│   ├── CNS vasculitis
│   ├── Neuropsychiatric SLE
│   └── MS / neurosarcoidosis
│
├── METABOLIC / TOXIC
│   ├── Wernicke-Korsakoff (thiamine ↓)
│   ├── Vitamin B12 deficiency
│   ├── Wilson disease (copper)
│   ├── Mitochondrial disorders (MELAS)
│   ├── Alcohol-related
│   └── Drug toxicity (lithium, methotrexate)
│
├── INFECTIOUS
│   ├── HIV dementia
│   ├── Neurosyphilis
│   ├── Viral encephalitis
│   ├── Cryptococcal meningitis
│   ├── Tuberculosis
│   └── Whipple disease (PAS+ macrophages)
│
├── PRION
│   └── CJD (sporadic/variant/familial/iatrogenic)
│       — Rapidly progressive, myoclonus, EEG periodic complexes
│
├── NEOPLASTIC
│   ├── CNS lymphoma
│   ├── Gliomatosis cerebri
│   └── Paraneoplastic / cancer-associated encephalopathy
│
├── STRUCTURAL
│   ├── Normal-pressure hydrocephalus (triad: gait, incontinence, dementia)
│   ├── Chronic subdural hematoma
│   └── Intracranial tumours (meningioma)
│
└── STORAGE / GENETIC
    ├── Niemann-Pick type C
    ├── Metachromatic leukodystrophy
    ├── CADASIL
    └── Down syndrome (Trisomy 21)

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CLINICAL APPROACH — FLOWCHART

Patient < 65 yrs with cognitive decline
              │
              ▼
     EXCLUDE PSEUDODEMENTIA
     Depression (masked depression in elderly)
     Schizophrenia (usually younger, delusions prominent, memory intact)
              │
              ▼
     HISTORY
     ├── Pattern of onset (acute/subacute → vascular, autoimmune, prion)
     ├── Family history (Huntington, CADASIL, FAD, prion)
     ├── Drug/alcohol history
     ├── Systemic features (rash → SLE, chorea → Huntington)
     └── Rate of progression (weeks–months = rapidly progressive dementia)
              │
              ▼
     EXAMINATION
     ├── Frontal lobe signs → FTD
     ├── Chorea → Huntington disease
     ├── Parkinsonism → DLB, CBD, PSP
     ├── Myoclonus → prion, metabolic
     ├── Cerebellar signs → MSA, mitochondrial, prion
     └── Kayser-Fleischer rings → Wilson disease
              │
              ▼
     INVESTIGATIONS (TIERED)

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INVESTIGATIONS — FLOWCHART

TIER 1 — ALL YOD PATIENTS (Minimum workup)
├── FBC, ESR, CRP
├── Metabolic panel (renal, LFTs, glucose, calcium)
├── TFTs (hypothyroidism → reversible)
├── Vitamin B12, folate, thiamine
├── HIV serology
├── VDRL/TPPA (neurosyphilis)
├── Lipid profile
└── MRI brain (mandatory — rule out structural/vascular/atrophy pattern)

TIER 2 — BASED ON HISTORY/SUSPICION
├── EEG (non-convulsive status, prion)
├── Genetic testing: HTT CAG repeat (Huntington), NOTCH3 (CADASIL)
├── Autoimmune panel: ANA, ANCA, anti-dsDNA, complement
├── Paraneoplastic antibodies (anti-Hu, Yo, Ri, NMDAR, LGI1, CASPR2)
├── Copper/ceruloplasmin/24hr urine copper (Wilson disease)
├── Lactate/pyruvate, mitochondrial DNA (mitochondrial disease)
├── Lysosomal enzyme assays (storage diseases)
├── Chest X-ray / CT chest (sarcoidosis, TB, malignancy)
└── CSF analysis:
    ├── Cell count, protein, glucose, VDRL
    ├── 14-3-3 protein, tau, RT-QuIC (prion)
    ├── Amyloid-β, phospho-tau (Alzheimer)
    ├── Oligoclonal bands (MS)
    └── Cytology (CNS lymphoma, leptomeningeal)

TIER 3 — SPECIALIST/RESEARCH
├── PET: FDG-PET (metabolic pattern), amyloid PET, tau PET
├── SPECT: DaTscan (dopaminergic) for DLB
├── Brain biopsy (CNS vasculitis, lymphoma, prion if uncertain)
└── Skin biopsy (CADASIL — electron microscopy GOM deposits)

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KEY DIAGNOSTIC CLUES — VIVA TRAPS

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TREATABLE / REVERSIBLE CAUSES — MUST NOT MISS

REVERSIBLE YOD
├── Hypothyroidism
├── Vitamin B12 / thiamine deficiency
├── Wilson disease (penicillamine / trientine)
├── Neurosyphilis (penicillin)
├── HIV (antiretrovirals)
├── Autoimmune encephalitis (steroids, IVIG, plasma exchange)
├── CNS vasculitis (immunosuppression)
├── Normal-pressure hydrocephalus (VP shunt)
├── Chronic subdural haematoma (drainage)
├── CNS lymphoma (chemotherapy ± radiotherapy)
├── Cryptococcal meningitis (antifungals)
└── Drug toxicity (withdrawal of offending agent)

A key viva point: ~20% of YOD cases have potentially treatable aetiologies — this justifies a thorough workup in every case.

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GENETIC YOD — SUMMARY TABLE

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MANAGEMENT FLOWCHART

DIAGNOSIS CONFIRMED
      │
      ├─── SPECIFIC TREATMENT (if treatable cause)
      │
      ├─── SYMPTOMATIC PHARMACOLOGICAL
      │     ├── Cognitive: Cholinesterase inhibitors (AD, DLB)
      │     ├── Behavioural: SSRIs (FTD, depression)
      │     ├── Psychosis: Quetiapine (avoid typical antipsychotics in DLB)
      │     └── Chorea: Tetrabenazine (Huntington)
      │
      ├─── NON-PHARMACOLOGICAL
      │     ├── Cognitive stimulation therapy
      │     ├── Occupational therapy / ADL support
      │     ├── Speech & language therapy
      │     └── Carer education & support
      │
      ├─── SOCIAL / LEGAL
      │     ├── Driving cessation (early counselling)
      │     ├── Power of attorney / advance directives
      │     ├── Work/financial planning (younger patients still employed)
      │     └── Child/family counselling (genetic implications)
      │
      └─── SPECIALIST REFERRAL
            ├── Neurologist (diagnosis, imaging, genetic)
            ├── Neuropsychologist (formal testing)
            ├── Geriatric psychiatry (BPSD management)
            └── Genetic counsellor (hereditary causes)

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VIVA KEY POINTS — CRISP ANSWERS

1. Definition: YOD = onset < 65 yrs; strict definition < 45 yrs (Mayo/Kelley)
2. Most common cause <45: Frontotemporal dementia + Huntington disease
3. Most common cause 45–65: Alzheimer disease
4. Most important distinction from late-onset: Higher proportion of treatable/reversible causes; genetic aetiology more prominent; social consequences more severe (employment, childcare, finances)
5. Why investigate thoroughly?: ~10–20% have treatable causes; missing them is catastrophic
6. Fastest to diagnose (must not miss): Autoimmune encephalitis, neurosyphilis, B12/thiamine, hypothyroidism, NPH, subdural haematoma
7. Rapidly progressive YOD → prion disease until proven otherwise; send RT-QuIC, 14-3-3, EEG
8. CSF biomarkers in AD: ↑ p-tau, ↑ t-tau, ↓ Aβ42
9. DLB: Never give typical antipsychotics — risk of severe neuroleptic sensitivity reaction
10. FTD vs AD: FTD = personality/behaviour change first, memory relatively preserved early; AD = memory loss first

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