This document discusses Alzheimer's disease and other dementias. It defines Alzheimer's disease as a neurodegenerative disease caused by amyloid plaques and tau tangles in the brain. It differentiates Alzheimer's from other dementias such as frontotemporal dementia, dementia with Lewy bodies, Parkinson's disease dementia, and normal pressure hydrocephalus. The document discusses risk factors, symptoms, diagnostic tools, treatments, and future targets for therapies for Alzheimer's and other dementias.

1. ALZHEIMER’S DISEASE
AND OTHER DEMENTIAS
ARLYN M.VALENCIA, M.D.
NEUROLOGY CENTER OF LASVEGAS

2. OBJECTIVES
Discuss the clinical and pathologic features of
Alzheimer’s Disease
Differentiate Alzheimer’s Disease from other dementias
-Vascular Dementia
-Frontotemporal dementia
-Dementia with Lewy Bodies
-Parkinson’s Disease Dementia
-Normal pressure hydrocephalus
-Mixed dementias
-Pseudodementia
Discuss the different stages, diagnostic tools and
treatment of AD
Share the challenges of future targets for
pharmacotherapy, diagnosis using biomarkers and
genetic testing, resulting public panic over the
rampancy of the disease

5. WHAT IS ALZHEIMER’S
DISEASE
 Neurodegenerative
disease of cerebral
cortices, starts in
hippocampus
 Abnormal deposits of
proteins: amyloid plaques,
tau tangles

6. Tangles and Plaques
 Amyloid plaques:
extracellular despoists
primarily of amyloid-B-
peptides
 Neurofibrillary tangles:
intraneuronal aggregates
of hyperphosphorylated
tau
 Tau : protein stabilizing
microtubules

7. PLAQUE

8. TAU TANGLES

9. DISEASED NEURON

11. Risk Factors For AD

12. AD AND THE OTHER DEMENTIAS

13. Frontotemporal Dementia

14. Frontotemporal Dementia
-Apathy, abulia or an unwillingness to
talk
-Change in personality and mood
-Lack of inhibition or lack of social tact
-Obsessive or repetitive behavior, such
as compulsively shaving or collecting
items
-Unusual verbal, physical or sexual
behavior
-Weight gain due to dramatic overeating

15. Dementia With Lewy Bodies

16. Lewy Body Dementia
 Neurodegenerative disorder characterized
by dementia, fluctuations in mental status,
hallucinations, and parkinsonism.
 Second most common cause of dementia,
following Alzheimer's disease. presence of
 Lewy bodies (abnormal deposits of a protein
called alpha-synuclein) in the brain.

17. Depression, hallucinations

18. Most Common Symptoms Of LBD
 Fluctuations in cognition, attention or alertness
 Problems with movement including tremors, stiffness, slowness
and difficulty walking
 Visual hallucinations (seeing things that are not present)
 Sleep disorders, such as acting out one’s dreams while asleep
 Behavioral and mood symptoms, including depression, apathy,
anxiety, agitation, delusions or paranoia
 Changes in autonomic body functions, such as blood pressure
control, temperature regulation, and bladder and bowel function.
 Impaired thinking, loss of executive function, memory, or the
ability to understand visual information

19. Parkinson’s Disease

21. Normal Pressure Hydrocephalus

22. VP SHUNTING FOR NPH
 One review found a pooled mean shunt complication rate of 38%
and an overall combined rate of permanent neurologic deficit
and death of 6%.
 Another publication reported mortality rates between 5% and
15% for the shunting procedure
 SINPHONI multicenter trial (Class III), 22% of shunted patients
experienced significantAEs. In addition to costs of
hospitalization and surgery, patients with implanted shunts are
at risk of shunt failure, ventriculitis, and shunt infections.The
prolonged lumbar drainage diagnostic procedure is associated
with a risk of meningitis and death of 1.8% to 3.6% and 0.2%,
respectively. Several more recent studies on shunting describe
complication rates of 15% to 28%.
 The educational content of this guideline was affirmed by the
American Association of Neurological Surgeons and the Congress
of Neurological Surgeons.

23. Triad Of NPH
 Dementia
 Ataxia/gait
apraxia
 Urinary
Incontinence

24. PD DEMENTIA AND LBD

25. ACETYLCHOLINESTERASE INHIBITION

26. Vascular Dementia
-Ischemic injury
-Anoxic insults
-The “silent
strokes” or “mini
strokes” of the
Hypertensives
Diabetics
Dislipidemics
Smokers

27. Mixed Dementia
 Advanced age is a risk factor
for all dementias and the
significant co-morbid
conditions such as stroke,
HTN, DM,cardiac disease

28. PSEUDODEMENTIA
DEMENTIA
DEPRESSIVE
PSEUDODEMENTIA
 Rapid onset
 Short-term
symptomatology
 Consistently depressed
mood
 Short answers (“I don’t
know.”); negativism
 Highlighting amnesia
 Fluctuating cognitive
impairment
 Gradual, progressive onset
 Long-term
symptomatology
 Mood fluctuations
 Tries to answer
 Conceals amnesia; later,
not aware
 Constant cognitive decline

33. AD BIOMARKERS IN RELATION TO IMAGING AND
CLINICAL PICTURE

34. CSF BIOMARKERS
 B-amyloid1-42 (Abeta1-42/Abeta1-40
ratio)
 T-tau and ptau181p
 Proven diagnostic accuracy for MCI
and AD
 Normal range rules out AD

35. FAMILIAL VS SPORADIC AD

36. FDA APPROVED DRUGS
Treat the symptoms of Alzheimer's disease.
 Donepezi/lAricept-All stages ; 1996
 Galantamine/Razadyne-Mild to moderate ;
2001
 Memantine/Namenda-Moderate to severe;
2003
 Rivastigmine/Exelon--All stages; 2000
 Donepezil and memantine/Namzaric-
Moderate to severe; 2014

37. STOP, SLOW, PREVENT AD


38. AD DRUG DEVELOPMENT PIPELINE

39. TARGETS FOR FUTURE THERAPY
 Towards beta-amyloid:
1. block beta secretase
2. prevent beta amyloid clumping into plaques
3. use antibodies to clear beta amyloid protein
ADUCAMUMAB-monoclonal ab, erly stage AD
2 Phase 3 trials underway 2019: to slow
cognitive and fucntional decline

40. 2. BETA SECRETASE (BACE)
 JNJ-54861911-PHASE 3
 2024
 -No Alzheimer’s
symptoms but high
brain beta amyloid

41. 3. TAU PROTEIN
 AADvac 1:
--vaccine stimulates
immune system to
attack abnormal tau
protein
--stop progression of AD
--Phase 2 : 185 volunteers
mild AD
3-20152-2019

42. 4. INFLAMMATION
 Microglia: first responders
to beta- amyloid and tau;
overactivity destroys
neurons
SARGRAMOSTIM (LEUKINE)
GM-CSF stimulates
macrophages in the blood
and local brain immune
cells (microglia) to “eat
these proteins” and
possibly slow or stop
disease progression.

43. AD PREVENTION TRIAL
1. Anti-amyloid
Treatment in
Asymptomatic AD (A-
4)
SOLANEZUMAB
2. Dominantly Inherited
Alzheimer’s Network
Trials Unit (DIAN-TU)
 Alzheimer’s Prevention
Initiative
- Autosomal Dominant
ADTrial (ADAD)
Has the gene (2 copies
of APOE (e4), no
symptoms
CRENEZUMAB-Ab’s
against b-amyloid

44. 5HT 2A RECEPTOR INVERSE
AGONIST
 Overactive serotonin
“key and lock”-
>psychosis
 PRIMAVANSERIN/Nupla
zid mimics serotonin key,
reduces communication
between neurons
 Decreases symptoms of
AD psychosis
 Phase 3

45. FOOD AND DIET IN AD: JUST THE FACTS
 MEDITERRANEAN
DIET
 COFFEE
 NUTS
 RESVERATROL
 CDP-CHOLINE
 CHOCOLATE

46. GET UP:LET’S ALL BE BRAIN HEALTHY
 EAT HEALTHY
 PLAY A MUSICAL
INTRUMENT
 INCREASE PHYSICAL
AND MENTAL ACTIVITY
 WHEN IN DOUBT IF
DEMENTED, CHECKTHE
FACTS AND ALWAYS
ASK A PROFESSIONAL
 VOLUNTEER!!!