Preserving Cognitive & Mental Capital in Our Knowledge-Based Economy

Husseini K Manji Global TA Head, Neuroscience Janssen Pharmaceuticals/J&J

OPINION | October 28, 2010

MORE MEDICAL RESEARCH IS NEEDED TO DEFEAT

ALZHEIMER'S DISEASE BEFORE IT'S TOO LATE TO

HELP THE BABY BOOM GENERATION.

Op-Ed Contributors: The Age of Alzheimer's

By Sandra Day O'Connor, Stanley Prusiner and Ken Dychtwald

“Alzheimer's disease,

an illness that is 100

percent incurable and

100 percent fatal”

“Starting on Jan. 1, our 79-

million-strong baby boom

generation will be turning 65

at the rate of one every eight

seconds. That means more

than 10,000 people per day,

or more than four million per

year, for the next 19 years

facing an increased risk of

Alzheimer's”

• 100 % incurable today

• 100% fatal today

• Numbers are going to

triple because of the

aging population

• >$1Trillion for care in

USA alone by 2050

Report from the Lewin Group, commissioned by the Alzheimer’s Association, Washington DC, 2004

Critical Need to Prevent Cognitive Decline

TODAY

TOMORROW 3

CSF Tau/Aß42 ratio predicts progression from MCI to AD over 5 years

Low Tau/Aß

High Tau/Aß

Ch

ance

of

no

pro

gre

ssio

n t

o A

D

Time (months)

Mood Disease Area Strategy

2.96

3.01

3.07

3.07

3.65

4.08

6.76

10.3

0 5 10 15

8. Cerebrovascular

Disease

7. Alzheimer's &

Other Dementias

6. Hearing Loss; Adult

Onset

5. Trachea / Bronchus

/ Lung Cancer

4. Chronic Obstructive

Pulmonary Disease

3. Alcohol Use

Disorders

2. Ischaemic Heart

Disease

1. Unipolar

Depression

0 10 20 30 40

Mental Illness*

Injuries, including self-inflicted

Alcohol and drug use

Malignant neoplasms (cancer)

Cardiovascular disease

Respiratory disease

Musculoskeletal disease

Sense organ disease

Digestive disease

Serious Mental Illnesses are Major Causes of Disability Worldwide: Global Burden of Disease

(U.S., Canada, and Western Europe 15-44 years old)

Disability-Adjusted Life Year (DALY)

Leading Individual Disease (DALY)

Disability-Adjusted Life Year (DALY)

Leading Disease Categories (DALY)

> 38,000 deaths by suicide annually in the US

Mental Illness*

1. Unipolar Depression

4

5

7-year follow-up of

6176 elderly women

< 6 depressive

sx

> 6 depressive sx

• Incidence of CV disease

• Outcome after CV disease

• Type II Diabetes

• Osteoporosis

• ? Risk of Dementia

• Mortality in Elderly

• Nursing home admission

Children of Depressed Moms are…

More likely to have poor academic performance

More likely to have behavioral problems

More likely to have a psychiatric illness

More likely to be hyperactive (boys)

More likely to have insecure attachments with their Moms

Hrs

pe

r n

igh

t

Sleep Duration Time Trends in US Adults

Highly Confidential—for discussion only

0.1% 1%

2%

6%

8%

9% 10% 10%

9% 9% 8% 8%

6% 6%

4%

3%

2% 1%

1% 0.3% 0.1%

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

PSQI Total Score: All Respondents PSQI Range: 0-20

Source: Sleep Study Maternal Health, April 2014, Total n=2,427

(Good) Sleep Quality (Poor)

Good Sleep Quality

25%

Poor Sleep Quality

75%

3 in 4 Women Report Poor Sleep During

Pregnancy

***

*** *** *** *

*

Prevalence of Comorbid Psychiatric Disorders in Individuals with Insomnia (Benca and Peterson, Sleep Med, 2008)

CV Disease Cancer Hypertension Respiratory Neurologic Urinary Diabetes Pain GI0

20

40

60 Insomnia (n=137)

No Insomnia (n=401)

Pre

vale

nce o

f M

ed

ical P

rob

lem

(%

)

** *** ** ***

***

*** ***

* **

Comorbidity of Chronic Insomnia with Medical Problems (Taylor et al, Sleep, 2007)

So we clearly need to D the Paradigm from Diagnose & Treat to Predict & Preempt: many challenges…….

• Need to be able to quantitate physiological/pathophysiological parameters, and intervene before transitions into more severe disease states

• Clinic visits are time-limited evaluations based on subjective observations of both the patient and the HCP

• Changes in disease state for each of these diseases can occur on timescales much shorter than the interval between clinic visits

• Through technological advances over the last decade it is now possible to objectively, remotely, and continuously measure aspects of patient physiology, behavior and symptoms

10

Emerging Technology for Continuous Patient Assessment

11

Symptoms

IVR

Smartphone Symptom assessment

Physiology

ECG HR/HRV Respiration Skin temp Activity/Sleep O2 sat

Behavior

GPS Talk patterns Text patterns Activity/Sleep

Escalating Data Challenge: How the types of data we collect is evolving…..

‘Point–of-Facility’ Discrete, Structured, Information Events Controlled Populations (clinical trials, longitudinal disease studies)

Physician Notes, EMR

Caregiver Reports

Literature Patents Epidemiology

E-mail,

‘Point-of-Need’ Real-Time Multiplexed Read-Outs (Diagnostic, Prognostic, Drug Monitoring) Distributed Populations in Clinic Settings

Semi-Continuous Semi-Structured data Multiple sources

Theranos

Discrete Centralized Discrete Decentralized Non-Discrete Decentralized

Diagnosis/ Prognosis

Drug Monitoring PK

....So Data is Evolving to Continuous Streams of Information ‘Quantified Self’

On-Patient

- Actigraphy

- Speech

- Eye movement

- EKG, HR, HRV

- EEG

- Sleep

- Galvanic skin

response

- O2 Sat

- Skin temperature

Off-Patient

- Fixed cameras

- Bed embedded

sensors

- Computer usage

- Phone usage

- Refrigerator

usage

- Motion sensors

Social Media

Brain Fitness Centers

Mobile Computing

Devices

Remote Monitoring

Sensors

New Data

Types, New

Tools for:

Information

Extraction,

Knowledge

Representation

Integration

Mining

14

EWSQ 10 Patient Version Potential Technology Correlates

Has your sleep worsened since the last evaluation? Sleep EEG Actigraphy

Has your appetite decreased since the last evaluation?

Has your concentration, e.g., ability to read or watch TV, worsened since the last evaluation?

Eye tracking Computer tracking

Have you experienced fear, suspiciousness, or other uneasy feelings while being around people since the last evaluation?

Skin Conductance Heart rate / variability

Have you experienced increased restlessness, agitation, or irritability since the last evaluation?

Actigraphy Galvanic Skin Response Speech Analysis

Have you noticed that something unusual or strange is happening around you since the last evaluation?

Have you experienced loss of energy or interest since the last evaluation?

Actigraphy Cell phone location

Has your capability to cope with everyday problems worsened since the last evaluation?

Have you experienced hearing other people’s voices even when nobody was around since the last evaluation?

Have you noticed any other of your individual early warnings signs since the last evaluation?

As we derive signatures of disease/relapse from the new continuous data types, we don’t have to start from scratch

these technologies use prior clinical knowledge, as well as the known history of the patients

Case Study I: Brain Health Registry Digital, Distributed Longitudinal Assessment of Cognition

Case Study II: Remote assessment of maintenance of treatment response in MDD patients

Behavioral assessment

Motor activity, sleep via actigraphy devices

Speech, voice via phone

Track trends

App collects and tracks

behavioral data

Assess self-report

Validated questions / scales (e.g., QIDS-SR)

administered via smartphone

Threshold level of decline

prompts alert to physician

Transmit information to clinician

a. Identify patients who may be at increased risk of near term relapse

b. Enable measurement-based changes to maintenance regimen

STAR-D: Subjects w/ greater number of residual symptoms after remission of MDD had a greater probability of relapse Nierenberg et al., 2010

Few studies have addressed predictors of near term relapse or onset of relapse prodrome in MDD

Preserving Cognitive & Mental Capital is Critical not only for

Individuals & Families, but also for Society

• Mood Disorders: very disabling

• Mood Disorders: associated with absenteeism, &“presenteeism”

• Societal productivity driven by quality of workforce; critical role of

cognitive & mental function

• Rapidly aging populations in Europe, US, Japan, and soon, China

equates to fewer working people per retired person

• We need people working later in life, but that requires preservation

of cognitive & mental capacity

Lake Nona may represent an ideal setting to undertake, integrate

& quantitate the impact of various interventions

Identification of at Risk & Early Diagnosis

Preserving & Restoring Cognitive & Mental Capital at Lake Nona

Computerized Cognitive Remediation

Cognitive & Mental

Function

Medical Nutrition

Therapeutics targeting Disease Pathology

Therapeutics targeting Neural & Synaptic Plasticity

Exercise