Early Features of Alzheimer's Disease
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For our biological foundations of memory class I prepared a 15 minute talk to present some of the symptoms, as well as neurological and cognitive manifestations of Alzheimers disease. I conclude by evaluating ERP work in Alzheimer's patients to further research on memory encoding and old/new effects.
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Early Features of Alzheimer's Disease
- 1. Memory Deficits in Alzheimer's Disease Image: http://www.caregivingclub.com/wp-content/uploads/2012/11/Memory-Loss-dreamstime_m_15669472-2.jpg
- 2. Consumer Reports Best Buy Drugs (2012)
- 3. Alzheimers Disease Symptoms • Earliest symptom = episodic • Encoding new information (Delis et al, 1991) • Delayed Recall Effects (Think Old/New effects) (Welsh et al, 1991) • Mild Cognitive Impairment (MCI) • Atrophy of relevant brain areas – Responsible for consolidation and retrieval – Mesial Temporal Regions Image: http://arealmummydiary.files.wordpress.com/2013/08/image-3.jpg
- 4. Preclinical Symptoms Small, Herlitz and Bäckman, 2004 • Episodic Memory Deficits – General in Nature • I.e. Both verbal and non verbal materials • Across Retention Interval • Across conditions (i.e. cued/free recall, recognition) • Mediated by Cognitive Support Image: http://arealmummydiary.files.wordpress.com/2013/08/image-3.jpg
- 5. Cognitive Support • Recognition tasks have the most cognitive support • Small et al, 1997 (See Small, Herlitz and Bäckman, 2004) – Tested memory tasks to see which predicted onset of AD Unsupported Supported • Significant effects in: recall of unlimited words • Recall of organisable words • Word and face recognition Deficits typical of ageing After multivariate analysis, only these two were significant predictors of a diagnosis.
- 6. Keller, Mackay, Barrick, Wieshmann, & Roberts, (2002).
- 7. Old/New Effects • Study context defined as ‘source’ Familiarity - NEW Recollection – OLD Recognition without retrieval of ‘study context’ (source) Recognition including recall of ‘study context’ • In healthy participants, trials may be contaminated by other recollective experiences • However: AD begins with impaired recollection
- 8. Hypothesis Rationale (Tendolkar et al, 1999) • Measured ability to recognise previously studied words and recollect study context • If AD patients cannot recollect contextual information, ERP old/new effect should be less contaminated by recollective processes than in healthy subjects. • Therefore: ERP readings should be more purely related to familiarity.
- 9. Methods: Study Phase • 10 Study phases of 10 words BOOK WINDOW • 500ms duration (5.5s interval) • Participants instructed to memorise word and presentation colour
- 10. Methods: Test Phase • 50% of words OLD; 50% of words NEW HOUSE BOOK • Participants asked to respond if they had seen the word prior • For words judged ‘old’, participants then asked to name the presentation colour
- 11. Results AD Patients Impairment to recollect study context Correctly recognised ‘old’ words more positive only between 300-500ms Peaks over frontal scalp Controls Sustained old/new effect Left temporo-parietal and frontal sides
- 12. Frontal peaks should give a more pure version of familliarity… But do they? The ERP’s (Tendolkar et al, 1999) FAMILLIARITY = NEW RECOLLECTION = OLD The OLD’s in Alzheimers are wherein they have defied the nature of their illness.
- 13. And Therefore..? • Hippocampal atrophy to blame for lack of temporoparietal old/new effect? • Symptoms typical of AD • But… why could patients with AD still encode some things with a flat-line ERP during the encoding of OLD items?
- 14. What does the competition say? • Debate as to whether semantic and episodic memories are tightly related (Tulving) or dissociated (Hodges & Graham) • An episode cannot be recounted first without going through semantic memory (Tulving, 1995; Tulving & Markowitsch, 1998) See Overman and Becker (2004)
- 15. Discussion • Is this a ‘process based dissociation’ – What is a process based dissociation? – What about this model from Tulving that suggests it is connected?
- 16. References Consumer Reports Best Buy Drugs. (2012). Evaluating Prescription Drugs to Treat: Alzheimer’s Disease. Retrieved from http://www.consumerreports.org/health/resources/pdf/best-buydrugs/AlzheimersFINAL.pdf Keller, S. S., Mackay, C. E., Barrick, T. R., Wieshmann, U. C., Howard, M. A., & Roberts, N. (2002). Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy. Neuroimage, 16(1), 2331. Overman, A. A., & Becker, J. T. (2004). Information Processing Deficits in Episodic Memory in Alzheimer’s Disease. In R. Morris, J. Becker (Eds.), Cognitive Neuropsychology of Alzheimer’s Disease (pp. 120-140). New York: Oxford University Press Inc. Small, B. J., Herlitz, A., & Bäckman, L. (2004). Preclinical Alzheimer’s Disease: Cognitive and Memory Functioning. In R. Morris, J. Becker (Eds.), Cognitive Neuropsychology of Alzheimer’s Disease (pp. 120-140). New York: Oxford University Press Inc.
Editor's Notes
- Take a look at these, I think many of them are actually semantic types, with some episodic memories intermingled.
- Delayed Recall Effects: A testing tool to distinguish mild dementure from normal older adults
- Explain what are perclinical symptoms?Cognitive support predictors = most persistent effect (Small, Herlitz and Baeckman, 2004)Retention interval – there are different measured memory deficits across different retention intervalsAcross conditions leads us on to cognitive support.
- Makessense, since old folks generally have age related symptoms of forgetting. However there are other tests that find no such effect.Key Results:Mean level significant differences for all tasksSignificant difference in task results between those that would get Alzheimers and those who would notMultivariate analysisFace recognition and organisable words predicted disease statusThese are definitely supportive activitiesAll at a three year follow up
- Explain Voxel Based MorphometryThis study came fromKeller, Mackay, Barrick, Wieshmann, & Roberts, (2002). – Credit where credit is due.The more yellow there is, the more atrophy is being represented.
- So, Alzheimers disease patients may be able to provide us with a more specific dissociation between familiarity and recollection brain activities.Just remember that the hypothesis rationale is coming up next.
- In our study there was also a significant difference between hippocampal volume of AD patients and controls. Both in left and right hemispheres.
- Old or new effect? Abstract says old, graph suggests new.
- New represents familliarity, aka the peak = semantic memory in actionFor most of the AD patiens, the old (aka recollection) is a flat line = no episodic activityIn controls there is a fairly wavy line showing an old new effect, demonstrating that everything is in order. So where does the dissociation come from?(IT IS A PROCESS DISSICIATION) – not a neurological correlate dissociation.AD patients – one component functions fine (i.e. Semantic Memory), but with depleted hippocampus, MUCH recollection fails, BUT NOT ALL. (Possibility that the small remaining bits of hippocampus are simply eliciting a the ‘quantitatively lesser effect’This is a PROPORTIONAL DIFFERENCE, which implies the process dissociation. The line is flatlined, but the fact that a reading has still taken place means something else in the brain is still operating episodic encoding.Interesting how that peak for the new effect doesn’t happen in controls. – See the green box – does it really respresent a ‘pure familliarity’ as was hoped for? Mini discussionRemember we are dealing with elderly people. Closely Matched ControlsEducationally matchedAge matched (e.g. variance)Gender Matched
- Less hippocampus, less ability to recall context/source, less old/new effectCould it be simply be a quantitively lesser measurement of a negligable old/new effect?i.e it’s still happening but barely measurable.But it’s not a proportional reduction, so it’s likely really that some other part of the brain is still encoding.