Correlation of Neuropsycholgy and Schizophrenia.pdf
August 10 presentation
1. “Brain Mechanisms of
Associative Memory Deficits
in Mild Cognitive Impairment
Patients, with and without
Parkinson’s Disease”
By
Tazrina Alrazi (PhD student)
The PCAN Lab
3. Mild Cognitive Impairment (MCI)
Normal
Cognition
Mild Cognitive Impairment
Dementia:
-Alzheimer’s dementia
-Lewy body dementia
-Parkinson’s dementia
4. Mild Cognitive Impairment (MCI)
-MCI in PD (PD-MCI) is potentially important for early identification and
intervention of PD patients who are at risk for developing dementia
-MCI encompasses all 5 cognitive domains
Executive functions
Visuo-spatial and visuo-perceptual functions
Memory
Attention
Language
5. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183–94.
6. Epidemiology of PD-MCI
• 26.7% (range 18.9–38.2%) of non-demented PD patients have PD-MCI
• Janvin et al. found 62% of PD-MCI patients converted to PDD over a 4-year
period, compared with 20% of PD patients with normal cognition
• The frequency of conversion to PDD over a 4-year period was:
multiple domain MCI (63%),
single, non-memory domain MCI (69%),
single domain, amnestic MCI (40%), and
normal cognition (20%)
Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, et al. MDS Task Force on
mild cognitive impairment in Parkinson's disease: Critical review of PD-MCI. Mov Disord. 2011;26:1814–24.
11. Candidate’s PhD Project
“Brain mechanisms of associative memory deficits in mild cognitive impairment patients, with
and without Parkinson’s Disease”
Hypothesis:
H1: PD, PD-MCI, non-PD-MCI, and healthy controls, as well as the PD/non-PD-MCI subgroups
(amnestic/non-amnestic, single/multiple domain) will exhibit significantly different associative
memory brain activation patterns.
H2: Lack of MTL compensation is an important marker of reduced cognitive performance in PD-
MCI and non-PD-MCI.
H3: PD-MCI vs. HC will show less MTL activation; PD-non-MCI vs. HC will show more MTL
activation.
12. Project Objectives
a) Characterize individuals with PD, PD-MCI, non-PD-MCI, and healthy controls
according to their associative memory profiles;
b) Compare the associative memory and neural characteristic between the groups,
PD, PD-MCI, PD-non-MCI, non-PD-MCI, and healthy controls;
c) Uncover the associative memory and neural characteristics within PD-MCI and
non-PD-MCI sub-groups (amnestic/non-amnestic, single/multiple domain).
13. Study Tools
Associative memory task
Neuropsychological assessments
Functional MRI
Data Analysis
-ANOVA
-General linear model (FSL software)
-Correlation analysis
14. Study Design
Participants:
Parkinson’s disease, no mild cognitive impairment PD (non-MCI) (35)
Parkinson’s disease with mild cognitive impairment PD-MCI (65)
Mild cognitive impairment, no Parkinson’s disease MCI (non-PD-MCI) (65)
Healthy Controls (age-matched to patients) HC (35)
Time point 1:
Training on a full version of the task outside the scanner (day 1)
Training on another mini version of the task right before scanning (day 2)
Scanning with the main full version of the task (day 2) (collecting fMRI data)
15. Associative Memory
“Associative memory is a form of episodic memory that has
been accepted to be resource demanding, necessitating persons
to learn individual items and the specific relationships between
the items”
“Associative memory task is more challenging long term
memory task than item memory”
Dennis NA, Turney IC, Webb CE, Overman AA. The effects of item familiarity on the neural correlates of successful associative memory encoding. Cogn Affect Beha Neurosci. 2015
16. Associative Memory Task
Associative memory tasks demand high efficiency of the medial temporal lobe
(MTL).
We hypothesize that reduced MTL BOLD (blood-oxygen-level-dependent
contrast imaging) activity during associative memory task will correlate with
reduced cognitive performance in our primary patient populations (PD, PD-MCI,
non-PD-MCI) which will reflect significantly in comparison of the subgroups
(amnestic/non amnestic; single/multiple domains). Do you like the pair?
27. Diagram of the Associative Memory Task
1st Run
Encoding:
2nd Run
Retrieval:
3rd Run, Encoding:
4th Run, Retrieval:
3 s
16 TRIALS/BLOCK = 152 s
16 TRIALS/BLOCK = 120 s 16 TRIALS/BLOCK= 120 s
Decisionmakingphasebegins
Same model
Same model
Doyoulikethepair?
Intactpair Initial locked period: 1 s
Response time : 5 s
After response locked period: 0.5s
Inter trial interval: 1 s
3 s3 s1 s
1 s
Memorizingphasebegins
Doyourecallseeingthesepictures?
3 s3 s3 s
Scrambledpair
Neverseenpair
Initial locked period: 1 s
Variable response time : 7 s
After response locked period: 0.5s
16 TRIALS/BLOCK = 120 s
16 TRIALS/BLOCK = 152 s16 TRIALS/BLOCK = 152 s
28. fMRI Data Analysis (Time 1)
Event related General Linear Model (GLM) contrast analysis (1st analysis) :
-Scrambled pair vs. Intact pair (posterior MTL)
-Scrambled pair vs. Never seen pair (frontal and temporal lobe)
-Intact pair vs. Never seen pair
-Inter group analysis (between four groups)
Second analysis:
-Looking at the effect of repetition within encoding
(use block number as covariate in the GLM design matrix)
29. Possible Outcome
In particular, we predict that in PD-MCI/non-PD-MCI reduced BOLD activity in
the MTL will correlate with decreased global cognitive performance.
Within PD with or without MCI, there may be different patterns of neural activity
observed in fMRI with this associative memory task corresponding to different
cognitive profiles. Some profiles will look more like non-PD-MCI while others
will be more different.
30. Importance of This Research
To date, no other research group has looked into the neural patterns of activity
linked to associative memory to compare reduced cognitive performance in PD
MCI and non-MCI which makes our research pioneering in this field.
This study will enlighten us on the importance of associative memory deficits in
PD with respect to global cognitive deterioration, as well as the differences
between the neural substrates linked to associative memory deficits in PD-MCI
and non-PD-MCI.
This will ultimately yield intervention and potential treatment strategies tailored
to different PD-MCI and non-PD-MCI patient subtypes, aimed at improving
cognitive deficits and decelerating the decline.
31. Student Update
Courses:
Neuro-1 (done)
Neuro-2 (done)
Neuroanatomy (done)
Advanced Imaging (attended, done)
Statistics (future goal)
Attends: Seminars in Movement Disorders, Cognitive Neurobiology, Hotchkiss Brain
Institute (HBI) seminars, Dementia rounds, Neuroimaging Journal Clubs and lab meetings
PCAN Lab activities: Dancing with Parkinson Disease, Science in
Theatre, Pedal for Parkinson’s…….
32. Collaborators
• Guy Rouleau, M.D., Ph.D.
CHUM, Ste-Justine, Université de Montréal
At University of Calgary:
• Dr. Bruce Pike
• Dr. Eric Smith
• Dr. Zahinoor Ismail
• Dr. David Hogan
• Dr. Justyna Sarna
• Dr. Angela Haffenden Tourmaline Oil Chair in Parkinson’s Disease
37. MRI Sequence
• MRI Time point 1 and 2 (anatomical and functional MRI):
• The first MRI session (Visit B) will include, a 5 min anatomical T1 weighted (IR-FSPGR=GENERL ELECTRI), a
6 min T2 sagittal FLAIR sequence, four 6 min task-based (episodic memory task) T2* BOLD fMRI sequences, and
a 10 min resting-state T2* BOLD fMRI sequence.
• The second MRI session (Visit C) will include a 5 min anatomical T1 weighted MP-RAGE, four 6 min task-based
(executive task) BOLD T2* fMRI sequences, and an SE-PI diffusion weighted acquisition with 64 directions
lasting 12 min.
• MRI Time point 3 (Visit B-alt)
• The MRI session will include, a 5 min anatomical T1 weighted
• MP-RAGE, a 6 min T2 sagittal FLAIR sequence, SE-PI diffusion weighted acquisition with 64 directions lasting
12 min, and a 10 min resting-state T2* BOLD fMRI sequence.
38.
39.
40.
41. Epidemiology of Parkinson’s Disease Dementia
• PDD can affect up to 50% of patients 10 years after diagnosis and over 80% by 20
years
• Dementia risk is almost 3-5 times higher in PD patients than in age-matched healthy
controls
• Severely affects quality of life, independent activities of daily living, and
interpersonal relationships
42. Epidemiology of Parkinson’s Disease
• Parkinson’s disease (PD) is the second most common
neurodegenerative disorder in the world
• In North America, the prevalence of PD is 107-187 per 100,000
population
• The most alarming non-motor PD complication is dementia (PDD)
43. Mild Cognitive Impairment (MCI)
Mild cognitive impairment (MCI) includes a change in cognition reported by
the patient, client, or clinician, objective evidence of impairment in one or more
domains, preservation in functional abilities, and not demented.
Qualitatively, MCI differs from both normal aging and dementia and is a risk
factor for the development of dementia in PD
44. PD-MCI
Frequency increases with:
More severe PD
Late disease onset
Lower educational levels
Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, et al. MDS Task Force on mild cognitive impairment in Parkinson's disease: Critical review of PD-MCI. Mov
Disord. 2011;26:1814–24.
45. Additional Analysis if Time Permits
Investigation of how these patterns of activation correlate with the different
neuropsychological and neuropsychiatric measures.
How these patterns of activation correlate with medial temporal lobe volumetry.
Finally, comparison of the patterns of neural activation between time 1 and time 2 (18
months after time point 1), and study whether a certain pattern of neural activation at
time 1 is predictive of faster cognitive decline.
The project is part of a larger longitudinal study looking into fronto-striatal circuit using
WCST, genotyping and anatomical analysis. If time permits I will do comparative
comparison with all these data collected via collaboration.
46. Mild Cognitive Impairment (MCI)
Normal
Cognition
Mild Cognitive Impairment
Dementia:
-Alzheimer’s dementia
-Lewy body dementia
-Frontotemporal dementia
-Parkinson’s dementia
-Vascular dementia
R. C. PETERSEN CLASSIFICATION, 2004
47.
48. Criteria for Amnestic-MCI (a-MCI)
• Memory complaint usually corroborated by an informant
• Objective memory impairment for age
• Essentially preserved general cognitive function
• Largely intact functional activities
• Not demented
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183–94.
aMCI: Prodromal AD
49. PD-MCI PDD
• Old age
• Male
• Lower education
• Longer duration of PD
• Greater motor impairment
52. Epidemiology of PD
• Parkinson’s disease (PD) is the second most common neurodegenerative disorder
in the world
• In North America, the prevalence of PD is 107-187 per 100,000 population
• The most alarming non-motor PD complication is dementia (PDD)
53. Epidemiology of PDD
• PDD can affect up to 50% of patients 10 years after diagnosis and over 80% by 20
years
• Dementia risk is almost six times higher in PD patients than in age-matched
healthy controls
• Quality of life, independent activities of daily living, and interpersonal
relationships
54. New Concept
PD-normal PD-MCI PDD
Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, et al. MDS Task Force on mild cognitive impairment in Parkinson's disease: Critical review of PD-MCI. Mov
Disord. 2011;26:1814–24.
Editor's Notes
You say: epidemiology and disease here
Pd is a Neurodegenerative disorder characterized by motor and non motor symptoms. Loss of dopaminergic substantia nigra neurons are principally responsible for the motor deficits. Etiology for non motor symptoms are still not clear.
Motor features are cardinally resting tremor, rigidity, brady kinesia but one of the most important non motor feature of pd is loss of cognition (most but nt all pd patients get it)
:…..motor features are which are asymmetrical in origin and presentation.
Non motor features among others are cognitive decline in the 5 identified domains namely……
Talk about the ad history that progessed to mci finding in pd
MCI is conceived as an intermediary stage between normal cognition and dementia. (because a few ppl goes back to normal may b due to improper diagnosis at the first place).
Initially this was proposed and very well studied as prodromal AD, but it was not well studied in PD. Now it is well accepted in PD. There was no clinical criteria until 2011, when mds task force recommended litvan to plan clinical guideline for mci in pd and later in 2012 litvan and collegues made the clinical criteria with level 1 and 2. level 1 is clinical diagnosis and moca and mmse. Level 2 includes all the neuropsychologcal assessments.
However, recent post-mortem studies suggest that between 30 and 45% of PD patients with dementia also meet neuropathological diagnostic criteria for AD [8]. With such a high proportion of demented PD patients with concurrent AD, it would be valuable, from a therapeutic standpoint, to identify those with AD earlier. In the context of the present proposal we will be able to follow longitudinally different groups of PD patients and compare them to non-PD amnestic MCI patients who are at risk of developing a medio-temporal lobe dementia such as AD.
This is one way of classifying pd cognitive deficits:
What are the other ways of classifying pd cognitive deficit?
This classification is dedicated to all mci both pd and non pd. And based on etiology there could be comparative comparison between different kinds of mci including pd and that is what we are trying to figure out what is the difference or correlation of neural origins in associative memory that I will do for my MCI patient population.
COGNITIVE DOMAINS MOSTLY TESTED NOW:
LANGUAGE, ATTENTION, EXECUTIVE FUNCTION, VISUOSPATIAL SKILLS
Single, non-memory domain MCI (69%) VS SINGLE DOMAIN, A MCI (40%)= It bypasses my hippocampus because that’s mostky related to memeory and if more non amnestics convert to dementia, that goes against my hypothesis of MTL involvement.
But this is not consistent and it varies a lot.
Many of the multi domain will convert to dementia…….our study looks more stuff than just MTL.
Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, et al. MDS Task Force on mild cognitive impairment in Parkinson's disease: Critical review of PD-MCI. Mov Disord. 2011;26:1814–24.
Janvin CC, Larsen JP, Aarsland D, Hugdahl K. Subtypes of mild cognitive impairment in Parkinson’s disease: progression to dementia. Mov Disord. 2006; 21:1343–1349. [PubMed:
This is the classic two pathway for cognitive decline proposed so far well accepted. My task mostly will focus on the posterior cortical pathways. And mildly frontal.
Dementia: A general term for a decline in mental ability severe enough to interfere with daily life.
Williams gray 2009 paper: 5 year longitudinal study:Figure 3 Schematic representation of hypothesized aetiological pathways leading to cognitive dysfunction in early Parkinson’s disease
and their relationship to the development of dementia 5 years later. ‘Frontal executive’ impairments in early disease appear to be a
consequence of a hyperdopaminergic state in the prefrontal cortex, which is in turn modulated by COMT genotype and dopaminergic
medication. These deficits are not associated with subsequent global cognitive decline and dementia over 5 years of follow-up. In
contrast, it seems that early deficits on more posterior cortically based cognitive tasks, which do develop into subsequent dementia, do
not have a dopaminergic basis. Rather, this work supports the hypothesis that they reflect Lewy body deposition in posterior cortical
areas, which is in turn influenced by MAPT genotype and the ageing process; PD = Parkinson’s disease.
This diagram is a review by Williams gray in 2014.
Most of PD patients develops dementia (PDD) in advanced stages of disease, but it affects over 80% of those with 20 years of disease[1] and a considerable number of them already shows cognitive deficits in the early stage so severe enough to be diagnosed as dementia.
AD ASSOCIATION
There has been a few studies supporting the idea that increased of mtl activation and compensation as well as cortical atrophy may be a marker of cognitive decline in pd. It includes a pet and an fmri study,an anatomical (all longitudinal, later two in ourys lab) but none of them includes a memory task like what I am doing here.
Alexandru paper: anatomical data: Cognition decline in PD is associated with temporal LOBE atrophy
Alexandru brain paper says: mtl atrophy
Oury’s study: (published)the better we have memory outside the scanner the better we use our hippocampus for wcst .
Unpublished oury data: longitudinal study shows that, the less u use hippocampus for wcst the more u will decline in the MocA (COGNITIVE EVOLUTION).
Eidelberg paper: Increased hippocampal activation in PD patient with sustained learning performance over time (longitudinal study) PET STUDY
Impairment of sequence learning is common in Parkinson’s disease (PD), but the time course of this
cognitive abnormality is not known. We assessed longitudinal changes in sequence learning
performance and associated task-related cerebral blood flow in 13 early stage PD patients who
underwent H2
15O PET at baseline and again two years later. Ten healthy volunteer subjects served
as controls. A trend toward decline in learning performance (p=0.08) was evident over the two years
of follow-up. During this interval, significant declines in learning-related activation were detected
in parietal and temporo-occipital association areas and in the right dorsolateral prefrontal cortex.
Learning-related activation in these regions was normal at baseline, but declined to subnormal levels
(p<0.01) at two years. Significant hippocampal activation (p<0.005) was present in the subjects with
high learning performance over time. The findings are consistent with a decline in learning-related
neural activity in cortical areas with prominent Lewy body formation.
Andrea paper:????
Nagano Paper: Better RAVLT scores correlated with increased activity in the (REY AUDITORY VERBAL LEARNING TASK)
hippocampus during set-shift execution, although this activity did
not appear for the contrast alone. This concurs with a longitudinal
positron emission tomographic study using visual-sequence
learning; the hippocampus was not solicited in control subjects,
but the best-performing PD patients (no decline) showed increased
hippocampal activation whereas poor-performing PD patients did
not (Carbon et al., 2010). These findings and ours suggest that PD
patients with preserved medial temporal lobe function may recruit
their hippocampus to compensate for striatal dysfunction, consistent
with medial temporal lobe atrophy in PD patients with dementia
compared with those without dementia (Nagano-Saito
et al., 2005) that is greater for PD patients with MCI than those
without MCI patients (Weintraub et al., 2011).
Oury unpublished data: global cognition: longitudinal study…. patients performing wcst task, people with higher hippocampal activity had higher moca scores and logitudinally they maintained higher moca scores vs ppl who had less hippocampal activity and lower moca in PD.
Sperling 2008 paper: Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer’s disease (AD)
have begun to reveal abnormalities in memory circuit function in humans suffering from memory
disorders. Since the medial temporal lobe (MTL) memory system is a site of very early pathology
in AD, a number of studies, reviewed here, have focused on this region of the brain. By the time
individuals are diagnosed clinically with AD dementia, the substantial memory impairments appear
to be associated with not only MTL atrophy but also hypoactivation during memory task
performance. Prior to dementia, when individuals are beginning to manifest signs and symptoms of
memory impairment (MCI), the hippocampal formation and other components of the MTL memory
system exhibit substantial functional abnormalities during memory task performance. It appears that,
early in the course of MCI when memory deficits and hippocampal atrophy are less prominent, there
may be hyperactivation of MTL circuits, possibly representing inefficient compensatory activity.
Later in the course of MCI, when considerable memory deficits are present, MTL regions are no
longer able to activate during attempted learning, as is the case in AD dementia. Recent fMRI data
in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in
the MTL memory system and in functionally connected brain regions, such as the precuneus. As this
work continues to mature, it will likely contribute to our understanding of fundamental memory
processes in the human brain and how these are perturbed in memory disorders. We hope these
insights will translate into the incorporation of measures of task-related brain function into diagnostic
assessment or therapeutic monitoring, such as for use in clinical trials.
Corresponding
Explain h3:
PD has more MTL activation than HC hence they are still non-MCI. However, PD-MCI is MCI because there is compensation which is not sufficient to help the deficit hence they are mci. And so the MTL activation pattern will be less roburst in them compared to PD-non-MCI and hc. So PD-non-MCI vs PD-MCI will show more MTL activation at PD-non-MCI. But it is possible when compensation of subgroups is happening that the non amnestic pd mci will not show this pattern and may have similar activation than the controls hc/mci non-pd; or even more.
Don’t say this: just for myself: When in aMCI, we cant predict that there is MTL atrophy, alex will help us measure that but I alone cant comment on that.
Also….there is initial hyperactivation for compensation, but when the mtl is affected and the compensaton is decresed…the grave cognitive deckine will pursue.
b) Name the groups
Multivariate analysis: andrea: ourys previous studies, answers my hypothesis questions.
Anova for behavoural data analysis
Glm for fmri data analysis
Glm: fmri y=xbeta+epsilon
Correlation for both behavior and fmri, correlational analysis will be done in glm followed by fdr for postdoc, attrition rate 15%, we will use t score for using it as covariate of importance (instead of z score). These scores are graded based on difeerent neuropsych assessments.
Correlation of z scores of neuropsych data and see who is deficit in what memory domain and what the circuit looks like for those defcits.
Answer: the better my memory, which regions I will use more….i am correlating this.
Add a fresh chart of the neuropsych
Whats driving the most cognitive deficit that
Fmri data parameters
Layers of data analysis: noemi
What do u mean by each version:
32 encoding pair is full
16 encoding pair is mini version
-Differences in the retrieval mechanisms underlying item and associative information:
-Item memory is supported by both recollection and familiarity, whereas associative memory relies primarily on recollection
-Interference associated with preexisting associations
-Increased workload imposed by the need to simultaneously learn both item and associative information
Moca correlation
Encoding pairs
OUR MODEL IS mixed (block design, 3s rest, hrf might coe to baseline) EVENT RELATED (it is event related ) JITTERED MODEL
Acquisitions per run: 120
Jittered: desynchronization between acquition and presentation.
We do jittered acquisition.
2.9 REPETITION time, slice per location 120…..so 2.9 is the time to acquire one whole brain image. We have 6min run with 14.5 s of dummy scans (5 scans). So our total actual acquisition per run is (6 x 60 -14.5)/2.9=120 almost.
Event related analysis, this is not regular and desynchronized, jittered presentation
We have resting stage between run 2 and 3: the benefit is cognitive to reduce the effect of first set of encoding. Recent see effect reduce; also forget the first run and second.
Option for second analysis: correlation analysis between the blocks. We will use blocks and events of those block as weight 1=b1, w2=b2,w3=b3; and correlate it to see the effect of repetiion of items. We are generalizing all the items thinking each trial is equal across al trials and subjects.
Some profiles will look same:
Amnestic single domain mci non pd and amnestic single domain pd might look the same and the ame degree of mtl activation. While other single domains or multi domains might look different, per say, executive pd single domain might not look the same as executive single domain mci.
Most mci that are amnestic, if progress, might progress to add, in od it s multi domain mci that mostly progress to pdd, for other domains we are still not sure which are the candidates and if they actually do progress and how.
MP-RAGE=SIEMENS
4. Hely MA, Reid WG, Adena MA, Halliday GM, & Morris JG (2008) The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord, 23, 837-844.
2. Zhang ZX1, Román GC. Worldwide occurrence of Parkinson's disease: an updated review. Neuroepidemiology.1993;12(4):195-208
3-5 eric smith
Mayeux R1, Marder K, Cote LJ, Denaro J, Hemenegildo N, Mejia H, Tang MX, Lantigua R, Wilder D, Gurland B, et al. The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993. m J Epidemiol. 1995 Oct 15;142(8):820-7.
3. Williams-Gray CH, Mason SL, Evans JR, Foltynie T, BrayneC, Robbins TW, & Barker RA (2013) The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J Neurol Neurosurg Psychiatry, 84, 1258-1264.
4. Hely MA, Reid WG, Adena MA, Halliday GM, & Morris JG (2008) The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord, 23, 837-844.
2. Zhang ZX1, Román GC. Worldwide occurrence of Parkinson's disease: an updated review. Neuroepidemiology.1993;12(4):195-208.
The definition of MCI according to the National
Institute on Aging-Alzheimer’s Association (NIA/AA)
workgroups diagnosis guidelines for AD (Albert et al.,
2011) includes a change in cognition reported by the
patient, client, or clinician, objective evidence of
impairment in one or more domains, preservation in functional
abilities, and not demented.
Litvan classification:
In PD (PD-MCI), is defined as “a cognitive decline that is not normal for age but with essentially normal functional activities, also appears to be common, even at the time of PD diagnosis and prior to initiation of dopaminergic therapy”.
Higher education is protective because of cognitive reserve, more flexible brain networks
This statement is true for sporadic pd only, otherwise monogenic od is prevalent as well
Such is smoking and caffeine
MCI is conceived as an intermediary stage between normal cognition and dementia. (because a few ppl goes back to normal may b due to improper diagnosis at the first place).
Initially this was proposed and very well studied as prodromal AD, but it was not well studied in PD. Now it is well accepted in PD. There was no clinical criteria until 2011, when mds task force recommended litvan to plan clinical guideline for mci in pd and later in 2012 litvan and collegues made the clinical criteria with level 1 and 2. level 1 is clinical diagnosis and moca and mmse. Level 2 includes all the neuropsychologcal assessments.
However, recent post-mortem studies suggest that between 30 and 45% of PD patients with dementia also meet neuropathological diagnostic criteria for AD [8]. With such a high proportion of demented PD patients with concurrent AD, it would be valuable, from a therapeutic standpoint, to identify those with AD earlier. In the context of the present proposal we will be able to follow longitudinally different groups of PD patients and compare them to non-PD amnestic MCI patients who are at risk of developing a medio-temporal lobe dementia such as AD.
TAKE IT OUT. ADD A RELATIVE COMPARISON BETWEEN ALL DOMAIN…TALK . Put in litvan criteria for diagnsis of mci
Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, et al. MDS Task Force on mild cognitive impairment in Parkinson's disease: Critical review of PD-MCI. Mov Disord. 2011;26:1814–24.
Mayeux R1, Marder K, Cote LJ, Denaro J, Hemenegildo N, Mejia H, Tang MX, Lantigua R, Wilder D, Gurland B, et al. The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993. m J Epidemiol. 1995 Oct 15;142(8):820-7.
3. Williams-Gray CH, Mason SL, Evans JR, Foltynie T, BrayneC, Robbins TW, & Barker RA (2013) The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J Neurol Neurosurg Psychiatry, 84, 1258-1264.
4. Hely MA, Reid WG, Adena MA, Halliday GM, & Morris JG (2008) The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord, 23, 837-844.
2. Zhang ZX1, Román GC. Worldwide occurrence of Parkinson's disease: an updated review. Neuroepidemiology.1993;12(4):195-208.
4. Hely MA, Reid WG, Adena MA, Halliday GM, & Morris JG (2008) The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord, 23, 837-844.
2. Zhang ZX1, Román GC. Worldwide occurrence of Parkinson's disease: an updated review. Neuroepidemiology.1993;12(4):195-208
LItVAN: accepts MCI as a prodromal stage of dementia in PD.
GRAY. Argues with this term as prodromal MCI because prodromal demetia in PD encompasses more but the hypothesis is: fronto striatal dopaminergic pathway affects motor symptoms mpstly and improves on dopamine therapy. But if only this pathway is affected then PDD is not gong to happen(frontal executive impairments). Whereas if posterior cortical pathways are affected which shows more like a cognitive deficit overall, pd will get pdd in 10yrs and it doesn’t improve with dopamine therapy.
