1. Memory Systems in Dementia
Andrew E. Budson, M.D.
Cognitive & Behavioral Neurology, VA Boston
Boston University Alzheimer’s Disease Center
Memory Disorders Unit, Brigham & Women’s Hospital
Harvard Medical School
Today I’m going to tell you about a clinical problem that I came across when I was a fellow in behavioral neurology, and share with you my research in this area.
I’m going to show you many experiments--not so that you’ll understand the details of all of them--but so you’ll get a sense as to some of the different experimental techniques which can be used to explore this issue.
I hope that my research will ultimately lead to an improved understanding of memory in general, the cognitive deficits of Alzheimer’s disease in particular, and therapies which can improve the lives of these patients and their caregivers.

2. Disclosures Royalties from Publishing for
Memory Loss, Alzheimer’s Disease, and Dementia: A Practical Guide for Clinicians, 2016 (Elsevier)
Seven Steps to Managing Your Memory: What’s Normal, What’s Not, and What to Do About It (Oxford University Press)

3. Long Term Memory
Episodic Memory
Semantic Memory
Procedural Memory

4. Episodic Memory
Personal, conscious, explicit recollection of experienced events framed in your own context
Where you parked your car
What you had for dinner last night
Anatomy:
Medial temporal lobe
limbic system
frontal lobes

5. Patient 1 Alzheimer’s disease 81 M with memory difficulties.
8 years ago got lost, began asking questions repetitively.
Gradual worsening, last 6-12 mos unable to learn new information
Remembers everything about his days during WWII
Alzheimer’s disease

8. From Budson & Solomon, 2016

11. Other diseases which can disrupt Episodic Memory
Tumors
Strokes
Hypoxic/Ischemic
Head Trauma

12. Ribot’s Law

13. The Papez Circuit

14. Episodic memory system

15. Hippocampal anatomy

17. Entorhinal cortex
Dentate gyrus
unique index assigned
CA3
Hilus
binding

19. Entorhinal cortex
Subiculum
Dentate gyrus
CA3
CA1
Hilus

21. Consolidation
Sleep
Dreams

22. Entorhinal cortex
Subiculum
Dentate gyrus
CA3
CA1
Hilus

23. 1 2 happy sad Day 1 Day 2 Day 3 ½ way down, on left
Red Blue
happy sad
½ way down, on left
½ way down, on right
All way down, on left
Day 1
Day 2
Day 3

24. 1 2 happy sad Days 2 & 3 Day 1 ½ way down, on left
Red Blue
happy sad
Days 2 & 3
½ way down, on left
½ way down, right OR
All way down, left
Day 1

25. Recently, an procedure has been developed which allows us to measure one type of memory distortion experimentally. To illustrate this point, I would like to give you all a memory test:
Are you ready?
I would like you to remember the following words:
candy, sour, sugar, bitter, good, taste, tooth, nice, honey, soda, chocolate, heart, cake, eat, pie.
OK, raise your hand if you remember that the word sugar was on the list.
flag;
sweet. Sweet was not on the list. This is one type of memory distortion--an example of a false alarm or false memory or false recognition.

26. Gist

27. 1 2 happy sad Days 2 & 3 Day 1 ½ way down, on left
Red Blue
happy sad
Days 2 & 3
½ way down, on left
½ way down, right OR
All way down, left
Day 1

28. Failure of source monitoring
Externally heard: sugar
Internally generated: sweet

29. B.G.

30. Frontal lobes in Episodic Memory
Memory for the temporal order of events
Memory for contextual information
Encoding information
Frontal and medial temporal lobes work together
Left brain for words, right for images

31. Left MTL & frontal lobes activated for words
Wagner, Schacter, et al., Science

33. Bilateral MTL & right frontal lobe for scenes

35. good idea Other cortical regions Frontal Lobes Medial Temporal lobes

36. Frontal lobes damaged  more work to get information in and out of storage.
Hippocampus/parahippocampal cortex damaged  impossible to get information in and out of storage.
Hippocampus/parahippocampal cortex damaged  Remote information that has been consolidated is available from other cortical areas.

37. Patient 2 Vascular Dementia Misattributes statements
74M 6 yr history of “Small TIAs.”
Misattributes statements
Confuses order and context of events
Variable performance on memory testing: from above average to extremely poor recall with preservation of recognition.
Vascular Dementia

41. Frontotemporal Dementia
Patient 3
78M with memory & behavior problems.
Frontal memory problems.
Extreme memory distortions:
Confused events on television with his own life
Frontotemporal Dementia

43. Normal Pressure Hydrocephalus
Patient 4
76F with poor cognition
impaired attention
Very poor recall but preserved recognition
magnetic gait disorder
incontinence
Normal Pressure Hydrocephalus

46. Patient 5 Alzheimer’s disease
79 F with memory problems, delusions and possible hallucinations.
Believed that she has recently spoken with her parents, long since deceased.
Believes that people are breaking into her apartment, stealing her money, and moving around her stuff.
Alzheimer’s disease

48. Red Blue
happy sad
Days 1, 2 & 3
½ way down, on left OR ½ way down, right OR All way down, left

49. “In NYC, the 53 bus will take you uptown: FALSE”
“It takes 32 coffee beans to make a cup of espresso: TRUE”
Neuropsychology

50. Illusory Truth Older Controls: Patients with AD
Remembered 77% of the true statements true
Remembered 39% of the false statements true
Patients with AD
Remembered 69% of the true statements true
Remembered 59% of the false statements true!!
Thus, if one tells a patient with AD, “The 53 bus will not take you to your sister’s house; take the 67 bus instead,” the patient will be likely to remember that the 53 bus is the one to take!
Neuropsychology

51. apple

52. Picture superiority effect

54. Semantic Memory
Our general store of conceptual and factual knowledge not related to any specific memory.
George Washington
Anatomy
Broad definition: Many cortical association areas
Words and their meanings: Lateral temporal lobes

55. Naming
Damasio et al., Nature

57. Patient 1 Alzheimer’s disease 81 M with memory difficulties
Word finding difficulties
Speech empty of content
Sentences do not make sense.
Difficulty with comprehension
Alzheimer’s disease

62. Patient 6 Semantic Dementia 63 F with language problems
Difficulty naming
Impaired comprehension of language
Impaired knowledge about the world
Easily found 10 hidden objects 20 min later
Directed daughter from NH to Boston easily
Semantic Dementia

63. Semantic Dementia Temporal variant of Frontotemporal dementia
Progressive atrophy of left > right temporal lobe

64. (all modalities of input and output)
Semantic Dementia
Impaired
Preserved
Semantic Memory
(all modalities of input and output)
Phonology, syntax
Problem solving
Visuospatial Perception

65. Picture Naming

66. Word to Picture Matching
Ball
Pear
Motor-cycle

67. Pyramid and Palmtrees Test

68. Drawing Object to Name
Sheep
Lamp

69. Knowledge of Correct ColorJL FM

71. Traumatic Brain Injury
Autobiographical memory?

72. Procedural Memory
Learning of behavioral & cognitive skills & algorithms that operate on an automatic, unconscious level
Riding a bike
Driving with a stick shift
Anatomy
Basal ganglia
Cerebellum

75. Parkinson’s disease

78. Patient
Controls

81. Rehabilitation Potential

82. end