Treatment: Lewy body disease and more Present and Future Bruce L. - - PowerPoint PPT Presentation

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Treatment: Present and Future

Bruce L. Miller, MD

A.W. and Mary Margaret Clausen Distinguished Professor in Neurology Director, Memory and Aging Center Co-Director, Global Brain Health Institute Joint Appointment in Psychiatry

Neurodegenerative Causes

Alzheimer’s disease frontotemporal dementia Lewy body disease and more

Dementia

cognitive decline that interferes with everyday functioning

memory, executive, behavioral, and/or motor symptoms

Neuropathologic Inclusions

AD

Aβ-42 & tau

FTD

tau or TDP-43

PSP, CBD

tau

PD, DLB, MSA

α-synuclein

CJD

PrPsc

AD & PD Spread Along Circuits

• Tau-positive neurofibrillary

lesions in AD (left, green)

• α-synuclein-positive

lesions (Lewy bodies & neurites) in PD & DLB

Goedert et al Trends Neurosci 2010

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Selective Vulnerability Brainstem Nuclei/Tauopathies

• Locus Coeruleus
• Dorsal Raphe Nuclei
• Substantia Nigra
• Gigantocellular Nuclei
• Pedunculopontine Nuclei

Eser et al Grinberg Lab JNEN 2018

Functional Connectivity Dorsal Midbrain Tegmental Network & Tau PET in PSP

2.5

Gardner et al. Ann Neurol 2013, Rabinovici 2015

Functional Connectivity Tau PET

Healthy Older Adult

PSP: Hyperarousal day & night CBS: Decreased arousal

24-Hour Sleep Patterns in Adults

Walsh... Neylan 2017 Sleep

Neurodegeneration Fiction & Facts

Fiction

1.

Degenerative disorders begin change in cognition or movement

2.

Psychiatric symptoms lack scientific relevance to dementia

3.

Mood disorders are a reaction to the illness

4.

Psychiatric symptoms in neurodegeneration irrelevant to typical psychiatric disorders

1.

Most start with psychiatric prodrome key to early intervention

2.

They are key to understanding neurodegeneration

3.

Mood changes reflects anatomy/chemistry of disease

4.

They are the roadmap for understanding mood, emotion psychosis, compulsions, etc. Fact

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Psychiatric Syndromes, Particularly Late in Life, Increase Risk for Dementia

• 13,535 patients, Kaiser Permanente
• 14% midlife depressive symptoms (45–60)
• 9% late life symptoms (60–75)
• Midlife symptoms increased risk
• f dementia by 20%
• Late life symptoms increased risk

by 70%

Barnes, Yaffe et al, Arch Gen Psychiatry, 2012

Psychiatric Changes in Dementia

Shdo, et al., submitted

Hypothesis

• Early changes in brainstem reticular core

(Braak stages 1–3): serotonergic, noradrenergic, and cholinergic systems disrupted  anxiety, depressive symptoms

• Amygdala sensitive to brainstem projection

changes  anxiety, depressive symptoms appear earlier than motor dysfunction

Braak et al., 2003

Psychiatric Disorders in PD

• 108 patients seen by psychiatrist (Seritan) from 2015–18
• Age: 63.7 ± 8.9 years
• Sex: 72 (66.7%) male
• PD diagnosis age: 52.8 ± 11 years

N (%) Patients with anxiety disorders

• Preceding PD diagnosis

72 (66.7) 40 (55.5) Patients with depressive disorders

• Preceding PD diagnosis

94 (87.0) 49 (52.1) Patients with anxiety & depressive disorders 63 (58.3)

Seritan et al., accepted

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Median Onset Ages For MDD, GAD, and Panic Disorder, Compared to General Population Median Onset Ages

N Min Median Max General population median onset age Sign test p-value MDD 39 8 46 74 29 < .0001 GAD 15 31 50 74 32 .0002 Panic disorder 13 20 59 71 24 .0005

N = number of patients with exact onset ages for this psychiatric disorder; Min = minimum age; Max = maximum age; GAD = generalized anxiety disorder; MDD = major depressive disorder. Seritan et al., accepted

worse p=0.008

20 40 60

1s 50 uV

1) Patient selection:

• Patients with PD
• with anxiety/depression
• Needing DBS to control

motor signs 2) Patients are implanted with a permanent ECoG strip over the PFC attached to an Activa PC+S

Minimal symptoms More severe

3) Brain signals are chronically Recorded in different mood states and paired with mood assessment using visual analogue scales on an IPad app (Moodify) 4) Each PFC recording is analyzed in the frequency domain and correlate with symptoms 5) PFC beta power (20-30Hz) correlates With the severity of anxiety and depression

Chronic Invasive Brain Recordings to Study Anxiety and Depression in PD Patients

De Hemptinne & Starr

p=0.008

More beta power in the prefrontal cortex is associated with more severe anxiety/depression

Recording contacts

Beta Power in the Prefrontal Cortex Correlates with Anxiety and Depression in PD Patients Early Changes in Emotion Accompany AD

• Emotional symptoms occur frequently
• In MCI (35–85%) and AD (75%)
• Anxiety and depression are most common
• With comorbid emotional symptoms there is:
• Worse function, higher risk of dementia conversion
• More rapid decline
• Increased salience network
• connectivity in AD (Zhou, 2010)
• Relates to agitation, irritability,
• aberrant motor behavior (Balthazar, 2013)

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BLSA Increasing Emotional Reactivity in Preclinical AD & Insula Hyperconnectivity

Fredericks et al., Alz Dement 2018 R

Antidepressant Use Associated with Lower Amyloid-β in Humans

• Retrospective analysis of PET scans
• Older adults with antidepressant treatment (trazodone)

in the past 5 years showed less amyloid-β accumulation

• Longer treatment time correlated with lower amyloid-β burden

Cirrito et al, PNAS, 2011 Rankin et al. Brain 2006

• R temporal pole
• R medial OFC
• R caudate
• R medial frontal

Only right hemisphere mediates these empathy changes

Loss of Empathy Relationship Turmoil and Empathy in FTD

• Marital dissolution and infidelity significantly greater in the

bvFTD group than nfvPPA, svPPA, CBS, PSP and AD

• Across all patients, empathy loss associated marital dissolution
• bvFTD patients who experienced marital dissolution or infidelity

had significantly lower empathy scores than those who did not

Takeda & Perry et al, submitted

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Caregiver Health Study

• 162 patients or healthy controls
• 35 Alzheimer’s disease
• 32 Behavioral variant FTD
• 15 Nonfluent variant FTD
• 23 Semantic variant FTD
• 17 Corticobasal Syndrome
• 17 Progressive Supranuclear Palsy
• 23 Healthy Controls

Measures:

• Structural MRI
• MMSE (cognitive functioning)
• CDR (disease severity)
• NPI (Neuropsychiatric Inventory)
• 162 caregivers or study

partners

• 83% spouses
• 63 years old
• 56% female
• 88% White American

Measures:

• SCL-90 (Psychopathology)
• SF-36 (Global Health)

Hua, Wells, Haase, Chen, Rosen, Miller, Levenson (accepted) Dementia and Geriatric Cognitive Disorders

Caregiver Psychopathology Patient Brain Caregiver Global Health

Covariates:

• caregiver age and sex
• patient diagnosis, disease severity, cognitive functioning, head size
• MRI scanner field strength

Hua, Wells, Haase, Chen, Rosen, Miller, Levenson (accepted) Dementia and Geriatric Cognitive Disorders

Consistent Neural Correlates of Worse Caregiver Health

Hua, Wells, Haase, Chen, Rosen, Miller, Levenson (accepted) Dementia and Geriatric Cognitive Disorders

Lifestyle Moderates Clinical Manifestation

• f Genetic FTD MAPT, GRN, C9orf72

*Adj. baseline frontotemporal volumes, age, sex, education, FTLD-CDR sum of boxes Casaletto, 2018

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Retraining Speech Production and Fluency in nfvPPA

• Treatment was repeated rehearsal of scripts via

structured treatment with a clinician as well as home practice

• Significant improvement in production of correct,

intelligible scripted words for trained topics, reduction in grammatical errors for trained topics, and overall increase in intelligibility for trained as well as untrained topics at post-treatment

• Follow-up testing revealed maintenance of gains

for trained scripts up to 1 year post-treatment

Henry et al. 2018

How? What are “modifiable factors”?

• Physical activity
• Cognitive stimulation/Education
• Diet
• Vascular disease
• smoking
• hypertension
• diabetes
• besity
• Stress
• Social engagement
• Head trauma
• Poor sleep
• Pollution

Physical Activity is Associated with Better Brain Aging

• Any type (almost), ≥moderate intensity, ≥45 minutes, any frequency
• Increased memory structures
• Better integrity of brain connections
• Less inflammation
• Associated with “super cognitive aging”

Increased Connection Northey et al., 2017; Erickson et al., 2011; Bott et al., 2017

Mental Stimulation & “Brain Training”

• ACTIVE Study: 10-year benefits of processing speed &

reasoning trainings

• UCSF Gazzaley Lab: Restore brain activity

to young adult levels

• Conversely…Watching TV
• >3hrs/day in mid-life  poorer cognition 25 years later

Thinking Speed

Rebok et al., 2014; Anguera et al., 2013; Hoang et al , 2016

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Mediterranean Diet Pyramid

• Follows general guideline (not specific

quantities), encourages communal eating and active lifestyle

• Higher adherence = Better cognitive
• utcomes
• Associated with:
• ~30% reduced risk of memory problems

and dementia

• ~30% reduced risk of stroke, diabetes,

and other vascular diseases

Oldways Preservation and Exchange Trust

MIND Diet

Mediterranean-DASH Intervention for Neurodegenerative Delay

Mediterranean diet + the DASH (Dietary Approaches to Stop Hypertension) diet, developed to ease hypertension

• Eat:
• Vegetables
• Green leafy

vegetables

• Berries, especially

blueberries

• Nuts (walnuts)
• Beans
• Wine
• Whole grains
• Fish
• Poultry
• Olive oil
• Avoid:
• Fried or fast food
• Red meats
• Cheeses
• Butter & margarine
• Pastries & sweets

Adherence to MIND Diet

SUVR = standard uptake value ratio on amyloid PET

0.5 0.7 0.9 1.1 1.3 1.5 1.7 3 4 5 6 7 8 9 10 11 12 13 SUVR MIND Diet Score

Adherence to MIND Diet associated with SUVR

Fox, Casaletto, et al, in press

Adherence to MIND Diet and Memory

Measured by TabCAT “Favorites” Memory Score

5 10 15 20 25 5 6 7 8 9 10 11 12 13 TabCAT "Favorites" Total MIND Diet Score

Adherence to MIND Diet associated with Memory Performance

Fox, Casaletto, et al, in press

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Age and Stress

Accelerated monocyte/macrophage cytokine trajectories in high stress

Casaletto et al, Am J Geriatr Psychiatry. 2018

Monocyte/Macrophage Cytokine Levels

Mediate relationship between age and executive function only in high stress

Casaletto et al, Am J Geriatr Psychiatry. 2018

Pseudomedicine for Dementia and Brain Health

• Supplements and medical interventions that are legal and

promoted as scientifically supported treatments without data

• $3.2 billion industry
• No known dietary supplement prevents cognitive decline or

dementia

How to Manage Pseudomedicine

• Understand motivations to pursue such interventions
• Provide honest scientific interpretation of evidence, risks and costs
• Label pseudomedicine interventions as such
• Differentiate testimony from data and assess scientific integrity
• Explore financial interests behind the intervention
• Educate on the US Dietary Supplement Health and Education Act
• Point out that effective interventions for common diseases would

already be widely used

• Express a willingness to continue to partner with patients in their

medical care

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Neurodegenerative Disease Therapies: Present and Future

Aimee Kao, MD, PhD Associate Professor Department of Neurology University of California, San Francisco 2018.07.27

To Cover

Recent Advances in Neurology 2019

• Current approaches to management of Alzheimer Disease and

related disorders

• Demystifying the drug development pipeline
• Biomarkers—what are they and how can they help?
• How basic science can lead to novel therapeutic targets

Disturbing statistics…

• AD is the 6th leading cause of death in the U.S.
• 5.7 million individuals affected by Alzheimer Disease (AD)
• 1 in 10 Americans aged 65 and older suffering from AD
• Between 2000 and 2015, cancer deaths have decreased

11% while AD deaths have increased by 123%

• In 2018, AD cost Medicare and Medicaid ~$277 billion
• By 2050: 16 million affected, $1.1 trillion estimated cost
• No disease modifying treatments or cures

Recent Advances in Neurology 2019

Current therapeutic approaches for Alzheimer Disease (AD) and Alzheimer Disease Related Disorders (ADRDs)

Pharmacological

• Acetylcholinesterase inhibitors
• Donepezil, rivastigmine, galantamine
• Most clear clinical benefit in Lewy Body Disease
• NMDA receptor antagonist (memantine)
• SSRIs and SNRIs
• For depression, anxiety and/or irritability
• Citalopram and escitalopram great for elderly population
• Anxiolytic (ie lorazepam) especially useful in Lewy Body Disease
• Neuroleptic (quetiapine) medications as a last resort

Recent Advances in Neurology 2019

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Current therapeutic approaches for Alzheimer Disease (AD) and Alzheimer Disease Related Disorders (ADRDs)

Behavioral Modification, Rehab and Support

• Exercise regimen +/- physical therapy
• Cognitive and speech training
• Home safety evaluation
• Fall prevention, family education
• Caregiver training and support
• Alzheimer’s Association (www.alz.org) and others
• Future planning

Recent Advances in Neurology 2019

The benevolent cycle of human disease research

Diabetes Heart disease CANCER Depression Epilepsy Multiple sclerosis Movement disorders Glaucoma An individual presents with a condition The condition is described More affected persons are identified Cohorts are

• rganized

Causes are identified (ie genetic, exposures) Disease mechanisms, biomarkers found Molecules are targeted for therapeutics Disease preventions are developed Disease treatments are developed

Recent Advances in Neurology 2019

Diabetes Heart disease CANCER Depression Epilepsy Multiple sclerosis Movement disorders Glaucoma An individual presents with a condition The condition is described More affected persons are identified Cohorts are

• rganized

Causes are identified (ie genetic, exposures) Disease mechanisms, biomarkers found Molecules are targeted for therapeutics Disease preventions are developed Disease treatments are developed

Recent Advances in Neurology 2019

The benevolent cycle of human disease research

Duenas et al, Brain 2006

Genetics

Gene mutation Gene dosage SNPs Epigenetics Molecules

Proteostasis

Lysosome/ATGome Proteosome ER stress HSPs Trafficking Prion/aggregation PTM

RNA

RNA Binding Proteins miRNA RNA foci/stress granules RNA structure

Synapses/activity

Excitotoxicity Selective vulnerability Synaptic dysfunction Axonal trafficking Microtubule stability

Aging

Oxidative stress Mitochondrial dysfxn Gene expression Cell quiescence

Potential Mechanisms of Neurodegeneration

Recent Advances in Neurology 2019

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Astrocyte Endothelial cell Microglial cell Injury/Environment

Traumatic Brain Injury Auto-immunity Complement Lipid Homeostasis Metabolism Heavy metals

Genetics

Gene mutation Gene dosage SNPs Epigenetics Molecules

Proteostasis

Lysosome/ATGome Proteosome ER stress HSPs Trafficking Prion/aggregation PTM

RNA

RNA Binding Proteins miRNA RNA foci/stress granules RNA structure

Synapses/activity

Excitotoxicity Selective vulnerability Synaptic dysfunction Axonal trafficking Microtubule stability

Aging

Oxidative stress Mitochondrial dysfxn Gene expression Cell quiescence

Potential Mechanisms of Neurodegeneration

Recent Advances in Neurology 2019

Dementia: The graveyard of therapeutics

• 2002 - 2012: 244 compounds, 413 clinical trials
• 0.4% success rate--lowest of any therapeutic area
• Since 2002, only memantine approved
• Trials: symptomatic (37%), disease-modifying small

molecules (35%) and immunotx (18%)

• Other drugs approved for AD pre-2002:
• donepezil (1997)
• rivastigmine (2000)
• galantamine (2001)

Cummings et al, 2014

Recent Advances in Neurology 2019

Some therapeutic avenues for neurodegeneration...

• Plaques: Prevent amyloid deposition
• Tangles: Prevent tau aggregation/PHF formation
• Microtubule stabilization
• Prevent neuronal dysfunction and death
• Oxidative stress
• Inflammation
• Neuroprotection

Recent Advances in Neurology 2019

Current Therapies in the Pipeline for AD

• Symptom reducing
• Cognitive enhancers
• Modify agitation, psychosis
• Disease modifying
• Decrease tau or amyloid
• Small molecule or immunotx
• Neuroprotection/regeneration
• Decrease inflammation
• Others

Recent Advances in Neurology 2019

Cummings, Lee, Ritter, Zhong 2018

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Current Therapies in the Pipeline for FTD spectrum

• Symptom reducing
• Cognitive enhancers
• Modify agitation, psychosis
• Disease modifying
• Decrease tau
• Small molecule or immunotx
• Neuroprotection/regeneration
• Decrease inflammation
• Others

Recent Advances in Neurology 2019

Per clinicaltrials.gov, August 22, 2018

The Long and Expensive Drug Development Pipeline

• A. Roses, 2008

Recent Advances in Neurology 2019

Targets

• What are the best ones?
• Where should targets be tested (model)?
• What is the basic biology of these diseases?

Recent Advances in Neurology 2019

Reasons for early failures in the development pipeline

Endpoints/study design

• Cognition and activities of daily living
• Blunt instruments—MMSE, CDR
• Methodological deficiencies
• Dearth of sensitive and specific biomarkers

Enrollment

• Lack of molecular diagnoses
• Phenotypically heterogeneous
• Genotypically heterogeneous
• Stage too advanced?

Recent Advances in Neurology 2019

Reasons for late failures in the development pipeline

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So, what about biomarkers?

The ideal biomarker

• Sensitive and specific
• Stable and reproducible
• Easily available
• Reflect a relevant disease process
• (Modifiable/responsive to therapy)

Recent Advances in Neurology 2019

Biomarkers can aid in

• Early and accurate diagnosis
• Symptomatic monitoring
• Develop new therapies

Biomarker: A quality, characteristic or substance that can be objectively measured as an indicator of a normal or disease process

Biomarkers are a bright spot...

• Plasma, CSF measures (Abeta, tau, Nfl, etc)
• MRIs and fMRIs
• Amyloid and tau PET
• Genes (Dominant, recessive and risk variants)
• Genetic risk scores
• Integration of clinical, translational, basic

science

Recent Advances in Neurology 2019

Developing therapeutics: Can we learn from other fields?

• Perspective: ~20 years behind cancer
• Needed:
• Better genetic and molecular characterization of

neurodegenerative disease

• Personalized approaches
• Understanding of the basic science!

Genes Pathology

The Knowledge Chasm

APP MAPT SNCA PGRN TARDBP C9ORF72 Plaques Tangles Threads Lewy Bodies TDP-43 inclusions Dipeptide repeats

(Potential therapeutic targets)

Recent Advances in Neurology 2019

Neurodegenerative diseases: Age-related disorders of selectively impaired protein homeostasis

Sequestration

Misfolded Properly folded

Age Stress Mutations a-synuclein LC/SNpc Pink, Parkin Ab and tau Ent Crtx APP, PSEN TDP-43 VEN/Motor N. Pgrn, CHMP2B Alzheimer’s Parkinson’s FTD/ALS

Degradation Proteosome Lysosome

X

Protein inclusion: Cell type of origin: Genes:

Recent Advances in Neurology 2019

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Genetic clues from neurodegenerative diseases from point to the importance of the lysosome

Mutation of genes involved in the endolysos

• mal pathway

ATP 13A2 (PD) CATD (AD) GBA (PD) P SE N1/2 (AD) VP S35 (PD) Ageing Mutation of genes encoding aggregate-prone proteins SNCA (PD) APP (AD) HTT (HD) MAPT (PD/AD) Gain of function Loss of function Lysosomal function and autophagy Enhanced protein aggregation (α-synuclein, HTT , Aβ-peptides and T au) Defective cellular clearance and accumulation of neurotoxic proteins Neurodegeneration P AR KIN (PD) P INK (PD) CHMP2B (FTD) R AB7 (CMT2B) WDR 45 (SENDA) F igure 3 | Defective cellular clearance in neurodegenerative dis eas es . Defective cellular Settembre, Nat Rev Mol Biol 2013

Pgrn TSC1

Recent Advances in Neurology 2019

A 55 yo RH man with 3 years of behavioral changes

HPI

• Presented with emotional flattening, social withdrawal, irritability

and loss of empathytreated for depression

• Progressively more disinhibited, alienating employees with

unwelcome and persistent practical jokes

• Compulsive internet searching

PMHx

• Multiple concussions
• Chronic HA
• Normal development

SoHx

• 13 yrs of education
• President of

construction firm

Olney et al, Acta Neuropathologica 2017

FamHx

• Epilepsy
• Cognitive dysfunction

Recent Advances in Neurology 2019

Neurological Exam

• Expansive mood, mildly intrusive
• O/w normal

Cognitive testing

• MMSE 26/30
• Memory: Impaired visuospatial > verbal
• Language: Impaired confrontation naming, semantic knowledge
• Executive function: Slow processing speed, decreased fluency

Exam and Cognitive Testing

Physical Exam

• Skin: Shagreen patch, ungual fibroma

Recent Advances in Neurology 2019

Olney et al, Acta Neuropathologica 2017

MRI reveals R > L temporal and frontal atrophy suggestive if bvFTD

Recent Advances in Neurology 2019

Olney et al, Acta Neuropathologica 2017

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International Research Criteria for Behavioral Variant FTD (bvFTD)

1. Early behavioral disinhibition 2. Early apathy or inertia 3. Early loss of emotional reactivity, sympathy and empathy 4. Perseverative, stereotyped or compulsive/ritualistic behavior 5. Hyperorality and dietary changes 6. FTD neuropsychological profile 7. Frontal or anterior temporal atrophy on MRI 8. Presence of known mutation

Rascovsky et al, Brain 2011

✓ ✓ ✓ ✓ ✓

?

Recent Advances in Neurology 2019

Whole exome sequencing identifies a novel loss-of- function variant in TSC1/Hamartin

II:2 Reference: C A T G C T G G G T G T G C G G G A C G A C G T G A C A II:1 Met Leu Gly Val Arg Asp Asp Val Thr C A T G C T G G G T G T G T G C G G G A C G A C G T G A Val Cys Gly Thr Thr STOP

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TSC1/Hamartin

Proband Affected sib

Recent Advances in Neurology 2019

Olney et al, Acta Neuropathologica 2017

Tuberous sclerosis complex

• A genetic disorder involving the growth of numerous benign

tumors in multiple organ systems

• Mutations in TSC1 or TSC2
• Incidence of 1/6,000
• Severity can vary widely between individuals
• In the CNS, cause cortical tubers, SEGAs, epilepsy,

intellectual disability, autism, other neuropsychiatric features

Recent Advances in Neurology 2019

TSC-Associated Neuropsychiatric Disorder (TAND) and bvFTD: Two sides of the same coin?

OCD Impulsivity Attention deficits Altered eating habits Repetitive behaviors Memory decline Language

TAND

De Vries et al, 2015

ASD Depression Language delay Sleep problems Self injury Anxiety

bvFTD

Aging Progressive Atrophy

Recent Advances in Neurology 2019

Rascovsky et al, 2011

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Frontotemporal Dementia (FTD) Spectrum Disorders

Recent Advances in Neurology 2019

Association for Frontotemporal Dementia

TDP-43 Tau Tuberous sclerosis has been called an “infantile tauopathy”

Sarnat 2012 and 2015

Phospho-Tau

Do TSC1 mutations lead to FTD?

Recent Advances in Neurology 2019

TSC1 mutation carrier with P-tau Frontal lobe resection tissue

Olney et al, 2017

2.2 0.0

L R L L 18F-AV1451-PET

Gil Rabinovici, Bill Jagust et al

TSC subjects with positive “Tau” PET

Areas of tracer uptake correlate with cognitive testing deficits

Multiple TSC1+/- cell and animal models exhibit abnormal tau accumulation

Kathleen Schoch and Tim Miller, Washington Univ

Total Tau (HT7)

Recent Advances in Neurology 2019

Control TSC1 mutation carrier

iNeurons Murine models Cell lines

Control Lamp2a PHF1 tau DAPI #1 #2 TSC1 +/- Carolina Alquezar-Burillo, UCSF

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TSC1: A potential new FTLD-tau gene

• Clinical, genetic, neuropathological,

imaging and experimental support

• Potential mechanism of action:

Increased mTOR activity and decreased protein degradation

• Age-associated lysosome changes

contribute to neurodegenerative disease

• Potential screening platform for tau

clearance?

TSC1/2 Rheb mTOR Growth Protein degradation

X

Tau clearance?

Recent Advances in Neurology 2019

Conclusions and future questions

Recent Advances in Neurology 2019

• Current therapies for AD and ADRD are limited and

symptomatically targeted

• Disease modifying drugs are in the development pipeline
• Understanding the basic biology of neurodegeneration will

lead to new and better target identification

• Personalized disease classification and therapies, a la
• ncology, are the wave of the future
• Anti-aging, rejuvenation therapies are under development as

well

Thank you!