Young onset dementia (YOD) refers to dementia with an onset before age 65. About 5% of all dementias are YOD. Common causes include Alzheimer's disease, vascular dementia, frontotemporal lobar degeneration, and dementia with Lewy bodies. A thorough evaluation includes medical history, physical and neurological exams, imaging like MRI and PET, and may involve genetic testing. Management focuses on treating underlying causes if possible, addressing behavioral and psychiatric symptoms, and providing social support. Prognosis varies by the specific cause but on average YOD results in 10-15 years shorter life expectancy than later onset dementia.

1. C
YOUNG ONSET
DEMENTIA
Dr Zuber Ali Quazi
Senior Resident
3rd Yr DM Neurology
GMC Kota

2. Introduction
o“Presenile Dementia”
• “Young-onset Dementia”,
• “Younger-onset Dementia”,
• “Younger people with Dementia”
Includes patients with onset of Dementia before 65 years of
age.
Rossor MN, Fox NC, Mummery CJ, et al. The diagnosis of young-onset dementia. Lancet Neurol 2010; 9: 793-806.

3. • About 5% of all Dementias.
• Estimated prevalence
• Overall = 119 per 100 000.
• b/w 30 & 45 yrs = 54 per 100 000.
• b/w 45 & 60 yrs = 98 per 100 000
• Incidence:- 11 per 100 000.
• Worldwide = Alzheimer's disease >> Vascular disease & FTLD.
• Japanese study = Vascular disease >> Alzheimer's disease.
Hendriks S et al.; Young-Onset Dementia Epidemiology Study Group.Global incidence of young-onset dementia: A
systematic review and meta-analysis. Alzheimer’s Dement. 2022;1-13.

4. •“Is this Young-Onset Dementia
or
is this Psychiatric?”.

5. When to suspect?
Individual who p/w :-
• New onset psychiatric symptoms with no previous psychiatric history.
• New onset - Middle Age (in past 10 years).
• Behaviour changes that are NOT consistent with previous personality
• Progressive Neurological symptoms or Seizures.
• Positive family H/o of YOD.
• Minimal improvement of psychiatric symptoms following
psychotherapy, counselling or psychotropic medications.
Red Flag
signs

6. History taking • Symptom onset and type
• Frontotemporal dementia symptoms (such as loss of empathy,
apathy, behavioural changes)
• Physical health and other medical conditions
• Function: eg, activities of daily living
• Drug and alcohol history
Family history • Obtain a three-generational history of young-onset dementia
Physical examination • Including Neurological Examination
Risk assessment • Occupational Risks, Driving, Other Risky Behaviour e.g, Gambling
Psychiatric assessment • Previous Psychiatric History & Symptoms
• History of Learning disability or intellectual disability
Neuroimaging • MRI Brain
Neuropsychological assessment • Screening testing.
Guidelines for assessment in young-onset Dementia
O’Malley M et al. International consensus on quality indicators for comprehensive assessment of dementia in young adults using a
modified e-Delphi approach. Int J Geriatr Psychiatry 2020; 35:1309-1321.

7. Etiology
• Alzheimer’s disease ------------------------------------30%
• Vascular dementia -------------------------------------15%
• FTD -------------------------------------13%
• Alcohol related dementia --------------------------------12%
• DLB ---------------------------------------------------4%
• Huntington’s disease
• Dementia in Multiple Sclerosis
• Dementia in Down’s syndrome
• Corticobasal Degeneration
• Prion disease
• Dementia in Parkinson’s disease
• Dementia due to carbon monoxide poisoning
25%
Sampson EL, Warren JD, Rossor MN. Young onset dementia. Postgrad Med J. 2004;80(941):125-139.

8. Reversible processes
• Chronic SDH
• Tuberculosis/Fungal Meningitis
• Brain Tumour
• Paraneoplastic Limbic Encephalitis
• Anti-VGKCC syndrome
• Hashimoto’s Encephalopathy
• Cerebral vasculitis
• Drug toxicities
• Whipple’s disease
Irreversible processes
•DLB, Alzheimer’s disease
•FTD
•Prion diseases: Sporadic,
Familial, & vCJD.
•PML
•SSPE

9. Dementia
plus
syndromes
Dementia
syndromes in
which Cognitive
Impairment is
accompanied by
additional
Neurological or
Systemic
features.

10. Ataxia
• SCA 2, 12, and 17
• Mitochondrial disorders,
• Multiple Sclerosis
• Alexander's disease
• Paraneoplastic diseases,
• Prion diseases (Familial forms & Variant CJD)
• Fragile X-Associated Tremor Ataxia syndrome
• Superficial siderosis
• Neuronal Ceroid Lipofuscinosis
• Niemann-Pick disease type C

11. Pyramidal signs
• Multiple sclerosis
• FTD with MND,
• Hereditary spastic paraparesis (SPG4),
• Adrenoleukodystrophy,
• Alzheimer's disease (some Presenilin mutations)
• Phenylketonuria,
• Vanishing White Matter Disease,
• Polyglucosan Body Disease,

12. Dystonia/chorea
•Wilson's disease,
•Huntington's disease & HDL syndromes
•Neuroacanthocytosis,
•PKAN (NBIA),
•DRPLA,
•Neuroferritinopathy,
•Anti-NMDA Receptor-Limbic Encephalitis,
•Variant CJD
•Neuronal Ceroid Lipofuscinosis (Facial Dyskinesia)

13. Bucco-Lingual mutilation
•Neuroacanthocytosis,
•Lesch-Nyhan syndrome

14. Akinetic-Rigid syndrome
•PKAN (NBIA)
•Wilson's disease,
•Dementia Pugilistica,
•DLB

15. Peripheral Neuropathy
•Porphyria,
•Alcohol-related Dementia,
•HIV infection,
•Mitochondrial disorders,
•Neuroacanthocytosis,
•Cerebrotendinous Xanthomatosis,
•Metachromatic leukodystrophy,
•Adrenoleukodystrophy

16. Dementia plus syndromes & Associated
diseases—Systemic features

17. • Myotonic Dystrophy,
• Cerebrotendinous
Xanthomatosis,
• Mitochondrial disorders
Cataracts
• Cerebrotendinous
Xanthomatosis
Tendon xanthomas

18. • Niemann-Pick disease type C,
• Gaucher's disease
Splenomegaly
• Polycystic Lipomembranous
Sclerosing Leucoencephalopathy
Bone cysts
• Vitamin B12 deficiency,
• Neuroacanthocytosis
• Wilson's disease
• Gaucher's disease
Anaemia

19. • Fabry's disease,
• Lesch-Nyhan syndrome,
• Mitochondrial disorders
Renal impairment
• Wilson's disease,
• Gaucher's disease,
• Mitochondrial disorders
Hepatic dysfunction

20. • FTD with MND,
• Perry syndrome,
• Mitochondrial disease (eg, POLG),
• Anti-NMDA Receptor-mediated
Limbic Encephalitis.
Respiratory Failure
• Coeliac disease,
• Whipple's disease,
• Porphyria
Gastrointestinal dysfunction

21. Alzheimer's disease
• Alzheimer's first patient was only 51 years at the time of presentation.
• Variants seen are
(i) Posterior Cortical Atrophy
(ii) Frontal Variant AD or Behavioural/Executive AD
(iii) Logopenic Variant Primary Progressive Aphasia
Sporadic Familial
Rare Common
(APP) and (PSEN1 and PSEN2) genes
Non-Amnestic Deficits
Executive Behavioural or Language
Dysfunction.
Episodic Memory Impairment
Myoclonus, Speech Production Deficits;
Naming- Preserved relatively

22. Vascular Dementia
•Subcortical Dementia
•Causes:-
Mitochondrial disease.
Cerebral Autosomal Dominant Arteriopathy with
Subcortical Infarcts & Leukoencephalopathy
(CADASIL)
PACNS

23. Dementia with Lewy bodies and
Parkinson's Disease Dementia
•Very rare.
•PDD
• Less frequently and with a longer latency in pts with YOPD.
• Common with :-
• α-synuclein Triplications &
• Mutations in the Glucocerebrosidase gene
• Rare with :-
• Parkin (PARK2) gene mutation.

24. Frontotemporal Lobar Degeneration
•Behavioural variant - most heritable
•Semantic variant - least heritable.
•Genes affected –
• Microtubule-associated protein tau (MAPT)
• Progranulin(GRN)
• Fused-in-sarcoma (FUS)
•Family history is positive ~up to 50%
•VEO-FTD (<45yrs)

25. Onset < 45 years -
Very Early Onset
FTLD (VEO-FTLD)

27. Dementia type Initial symptoms
Alzheimer disease Short term memory impairment
Word-finding difficulties
Disorientation
Posterior cortical atrophy Visual perception impairment
Alexia
Gerstmann syndrome
Behavioural variant FTD Behavioural and personality changes
Loss of empathy
Disinhibition
Changes in appetite
Apathy
Repetitive or stereotyped behaviours
Rigidity
FTD–MND Behavioural changes
Motor changes: weakness, UMN & LMN signs
Semantic dementia Semantic impairment
Anomia
Single word comprehension impairment
Progressive non-fluent aphasia Progressive speech production impairment
Halting, slow, Effortful speech
Motor speech apraxia

28. Investigations
• Routine Haematological & Biochemical blood tests - For Comorbidity
• Auto-antibodies, Antineuronal Ab, & Antibodies- Limbic encephalitis
- Rapid-onset dementias or with signs of Systemic disease.
• White cell enzyme & VLCFA assays - Metabolic disorders
• Multiple Blood Films - Neuroacanthocytosis.
• EEG:- AD, SSPE, FTD
• EMG:- Myopathy ; Myotonic Dystrophy; MND
• NCS:- Neuropathies

29. To Lumbar Puncture or Not to Lumbar
puncture?
•Aβ40, Aβ42
•Total tau (t-tau) &
•Phosphorylated tau (p-tau)
•Neurofilament Light chain :-
• Differentiate b/w:- Primary psychiatric disorders & YOD.
•Tumours & Infections
NPV = 98%
PPV = 77%

30. Genetic Testing
•About 15% c/b AD genetic mutation.
•Highly recommended -
Positive Family h/o YOD,
Onset <45 years of age.
With a Dementia type with a high Heritability Rate.
• Nearly 50% of people with onset <45 years = Directly inherited.

31. •Techniques available
(i) Targeted gene panels
-Include specific genes for a particular d/o
(ii)Whole Exome sequencing
(iii)Whole Genome sequencing

32. Genetic testing (….contd)
•Probable bvFTD with at least one first-degree relative with bvFTD, late-
onset PPD, ALS or other Early Onset Neurodegenerative disease = All FTD
mutations
•All cases with possible or probable bvFTD, regardless of family history
= C9orf72 mutation.
•Late-onset PPD with at least one first-degree relative with FTD or ALS =
C9orf72 mutation.
•All cases of suspected bvFTD not meeting full diagnostic criteria if there
is Prominent Psychiatric symptoms or Family h/o Late-onset PPD =
C9orf72 screening
Ducharme S et al. Recommendations to distinguish behavioural variant Frontotemporal Dementia from
psychiatric disorders. Brain. 2020;143(6):1632-1650.

33. Limitations
• Large duplications & Structural variations cannot be read by
these techniques,
• Triplicate repeat disorders (e.g HD, MD)
• Disorders related to the C9orf72 mutation.
• Clinical significance - Genetic variants ?

34. Ruling In:-
•Repeated Assessments:-
-Normal Neuropsychological testing
•Phenocopy syndrome.

35. Tissue Biopsy
•Skin biopsy- CADASIL, NPC.
•Muscle biopsy - Mitochondrial d/o
•Tonsillar biopsy – suspected vCJD
•Brain biopsy - [Exceptional cases]

36. Imaging

37. MRI Brain PET
Alzheimer disease Hippocampus
Medial temporal lobes
Precuneus
Posterior cingulate
Parietotemporal
Other Modality Amyloid-β PET

38. MRI Brain PET
Posterior Cortical Atrophy Posterior/occipital regions Parietooccipital cortices
Other Modality Amyloid-β PET

39. MRI Brain PET
Behavioural variant FTD Frontal (medial, orbitofrontal,
anterior insula)
Frontotemporal

40. MRI Brain PET
Semantic FTD Anterior temporal Frontal midline structure
(Cingulate, orbitofrontal &
Anterior Medial Cortices, Insula)

41. MRI Brain PET
Progressive Non-Fluent Aphasia Left-sided posterior
frontoinsular atrophy
Frontotemporal Region of Left Side: Inferior
Frontal Region, Dorsolateral Prefrontal, Broca
&
Wernicke Area & Inferior Temporal Regions.

42. Management
• Management of cardiovascular risk factors and other lifestyle modification.
• Suicide risk = 2.8 times.
• For young-onset AD,
-Donepezil, Memantine
• Low mood, Depression & Anxiety
-Psychotherapy &
-Antidepressants (Short term BZD)
• Sleep Disturbances
-Non-pharmacological
-Melatonin or Short term low dose BZD.

43. Prognosis

44. • Average time for diagnosis = 3.5 yrs
• Median Survival YOD d/t:-
AD = 11.3 years
FTD = 10.6 years
Vascular dementia = 12.3 years
• AD gene mutations (eg, MAPT-type FTD) - Earlier age of onset
& age at Death
• FTD a/w MND has the shortest duration of survival.
• Overall, people with YOD lose 10 to 15 years of life expectancy.
Loi SM et al. Time to diagnosis in younger-onset dementia and the impact of a specialist diagnostic service. Int
Psychogeriatr. 2022;34(4):367-375.

45. THANK
YOU

46. References
1. Rossor MN et al. The diagnosis of young-onset dementia. Lancet Neurol 2010; 9: 793-806.
2. Knopman DS et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the
Quality Standards Subcommittee of the AAN. Neurology 2001;56:1143–53.
3. Waldemar G et al. Diagnosis and management of Alzheimer's disease and other disorders associated
with dementia. The role of neurologists in Europe. EFNS. Eur J Neurol 2000;7:133–44.
4. Hendriks S et al.; Young-Onset Dementia Epidemiology Study Group.Global incidence of young-onset
dementia: A systematic review and meta-analysis. Alzheimer’s Dement. 2022;1-13.
5. O’Malley M et al. International consensus on quality indicators for comprehensive assessment of
dementia in young adults using a modified e-Delphi approach. Int J Geriatr Psychiatry 2020; 35:1309-
1321.
6. Ducharme S et al. Recommendations to distinguish behavioural variant Frontotemporal Dementia from
psychiatric disorders. Brain. 2020;143(6):1632-1650.
7. Dumba M et al. Clinical 18F-FDG and amyloid brain positron emission tomography/CT in the
investigation of cognitive impairment: where are we now?. Br J Radiol 2019; 92: 20181027.