# Presentation: 122326

## Speed of processing, the missing measure in early detection of MCI?

- Ruth O’Hara
- March 13th 2001

- Yogesh Shah

## MCI

- Introduction
- Early detection
- Speed of processing
- Study
- Conclusions

## 2001 and beyond

- $100 Billion/year
- Delay 2 years    – 2 million less AD
- Delay 6 months – $ 6 billion/year

## Early Detection

- Detection of preclinical cognitive deficits is important for identifying those at risk for Alzheimer’s
- Neuropsychological measures may not be sufficiently sensitive to preclinical cognitive impairment

## Normal Speed of Processing Decline

**Notes:**
Brain Processing Speed declines with age (ARMD) – Based on 4500 normal subjects

## Millisecond Difference

**“... ****the ****speed**** of memory performance may be the first aspect of the memory system to decline as the system begins to fail.”**** ****	****	****	*****Int’l Jnl Ger Psychiatry, Vol. 10: 199-206 (’95)***
**“... ****traditional tests for dementia were relatively ineffective for identifying its early forms. The only effective assessment... is one that measures both ****speed**** & accuracy.”****	****	**** *****Int Psychogeriatr, 1996;8(3):397-411***

## Millisecond Difference

**“...****research suggests that ****speed**** of performance may reflect the efficiency of mental processes.”****	****	****	****	****	**** *****Nature Neuroscience 2000; 3:509-515***
**“... ****speed**** scores identify impairments that would otherwise be missed using traditional measures. ...speed scores on measures of attention & memory... identify patients with MCI”.*****                                             ******	******	******	******  Research & Practice In Alzheimer’s Disease, Vol. 3, 2000***

## Millisecond Difference

**  **A few 100ms in processing speed may spell the difference between healthy & “unhealthy” brain

## Slower Reaction Time on Memory Tasks is Associated with Presence of the Apolipoprotein E4 allele: A Brief Report

- 	**Ruth O’Hara, Ph.D.,1 Barbara Sommer, M.D., 1 Helena C. Kraemer, Ph.D., 1 Jerome Yesavage, M.D., 1,2 Joy Taylor, Ph.D., 1,2  Kevin Morgan, B.A., 1  and Greer Murphy, M.D., Ph.D. 1**
**1 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA **
**2 VA Palo Alto Health Care System, Palo Alto, CA**

- Info@cogcare.com

## Reaction Time

- The ability of a computerized battery of neurocognitive tests (Cognometer) to differentiate between the cognitive performance of subjects with and without the 4 allele.

## Abstract

**Abstract**
**Detection of preclinical cognitive deficits is important for identifying those at risk for Alzheimer’s disease, but available neuropsychological measures may not be sufficiently sensitive to preclinical cognitive impairment, particularly in high functioning, younger older adults.  Utilizing a battery of computerized cognitive tests designed to provide a more sensitive measure of age-related cognitive performance, we compared the performance of 10 older adults with the AD risk-factor Apolipoprotein e4 allele with 17 older adults without the e4 allele.  This battery includes measures of attention, sensory-motor, visuospatial, working memory (executive) and delayed memory function, which incorporate reaction time components that reflect**** ****information-processing speed.**** The e4 group was significantly slower in performing all delayed memory and specific working memory tasks, although n****o significant differences were observed between the groups with respect to accuracy on almost all these measures. **** This suggests that reaction time performance on such memory and working memory measures might be able to detect subtle cognitive deficits, particularly in younger, older adults.****  **

## 						Abstract

**The ********4**** group was significantly ****slower**** in performing all delayed memory and specific working memory tasks, although ****n****o**** significant differences were observed between the groups with respect to ****accuracy.**

## Abstract

**Reaction time**** performance on memory measures might be able to detect subtle memory deficits, particularly in younger, older adults**** **

## Method

- 10 older adults with  Apolipoprotein 4 allele with 17 older adults without the 4 allele
- AGE- 74.6
- EDU- 16.2
- MMSE-26

## Stanford Apolipoprotein E4 allele  Cognometer Study

- *Executive decision-making, “set switching” task

## Individuals with the Apolipoprotein E4 allele Exhibit Significantly Slower Reaction Times on Cognometer Tests

**Notes:**
Higher bar = slower reaction time (or brain processing speed)

## Reaction Time-conclusion

- Individuals with the 4 allele have greater difficulty with the information processing involved in executive  and memory functions

## Reaction Time-conclusion

- Reaction time performance on memory measures might be able to detect subtle memory deficits, particularly in younger, older adults

## Current issues -MCI...

**Is there a frontal, executive deficit in MCI?**
**Are standard neuro-psych instruments sensitive to working memory deficits?**
**Can reaction time measures be meaningful outcome in anti-dementia drug trials?**

** **

**Notes:**
Study supports hypothesis of a continuum between AAMI & AD.

## Slide 20

## MCI – is there also a frontal, executive deficit?

*ADCS* – “patients with MCI perform worse on memory measures.... But equal to healthy people in other cognitive areas.”*
*Stanford ApoE4 study (et al)** suggests working memory processing **speed**           may also be a meaningful MCI measure.*

- *Alzheimer’s Disease Cooperative Study
- **“**speed** scores on measures of attention & memory... identify patients with MCI”;*  Research & Practice In Alzheimer’s Disease, Vol. 3, 2000*

## “...experience with cholinesterase inhibitors shows that other outcome measures may be more sensitive to drug effects... reaction time measures can be meaningful outcome measures in anti-dementia drug trials.”Lancet, Vol. 356, December 16, 2000; 

*Dr. Jeffrey Cummings, **Dept. of Neurology, UCLA*