Journal Club Article 1

“Influence of Education on Subcortical Hyperintensities and Global Cognitive

Status in Vascular Dementia”

Lane, Paul, Moser, Fletcher, and Cohen (2011). JINS, 17, 531-536

Department of Psychology, University of Missouri-St. Louis

Department of Psychiatry/Human Behavior, University of Iowa Carver College of Medicine and Brown University Medical School

Reviewer

• David M. Lechuga, Ph.D.– Neurobehavioral Clinic & Counseling Center– UCLA Semel Institute of Neuroscience and Human

Behavior

• Chair, Division of Neuropsychology– California Psychological Association

Vascular Dementia (VaD)

• Cognitive impairment due to cerebral vasculardisease– Sufficient to impact activities of daily living

• Possibly 2nd most prevalent type of dementia in US (after Alzheimer’s disease; AD)

• Debate– Independence of VaD from AD

VaD NP Profile & Pathology

• Intact recognition memory system and impaired executive functions– Relative to AD

• Expression is variable– Lesion size and location

• Affected areas– Subcortical regions of gray and white matter• Small anastomosing vessels that perfuse region

– Compromised with aging

Common Cognitive Deficits

• Slowed processing speed, memory impairment, executive dysfunction, and impaired language fluency

• Heterogeneity the rule– Depends on affected neural circuits

Subcortical Hyperintensities (SH)

• Hallmark feature of VaD– Necrotic, or inflamed tissue• Small subcortical strokes• Areas of bright white regions on T2 or fluid-attenuated

inversion recovery (FLAIR) MRI• May be related to vascular (hypertension) and

degenerative (e.g., brain shrinkage) factors, aging and disease• Possible blood-brain barrier failure and enthothelial

leakage

• Impaired PS and EFx

Mitigating Neuropathological Burden

• Higher education’s (life experience) role– Cognitive Reserve (CR)• Helps explain discrepancy between individuals with

similar levels of pathology, but different functional capacities

• Other factors– Linguistic ability– Active social lifestyles– Leisure activities

Individual Differences and CR

• Head circumference, brain volume, and synaptic density

• Perhaps associated with redundancy in normal brain networks– Increased cognitive strength and flexibility post

brain damage

CR and Other Conditions

• Traumatic brain injury, hepatitis C, vascular disease in non-demented individuals

• Further support for better outcome, associated with greater CR variables

Role of CR in VaD

• No studies, to date• Current work– Relationship between educational attainment, SH

volume, and global cognitive status in VaD sample– Mini-Mental Status Exam (MMSE) used

• Brief measure of global cognitive function• Screening tool used by physicians, routinely

– Hypothesis• Individuals with greater educational attainment will perform

better on MMSE that those with less education, regardless of amount of SH damage

Methods

• Participants– 36 (mean age: 77.56; SD = 5.71; mean education

= 12.03; SD = 3.38; range = 6-20 years)– Probable VaD• Extracted from larger cohort (late phase drug trial; no

effects)• Groups collapsed (tx and placebo)• Dx made by consensus

– NINDS-AREN and DSM-IV criteria

Dx Approach

• NP and neurological examination– Complete medical hx

• From patient and informant– Structural neuroimaging scans

• Study allowed for identification of “pure VaD”– No probable mixed dementia– Excluded other disorders

• Group consensus– <24 MMSE– Between 67 and 88 years of age

Procedures

• MRI first, the MMSE as part of larger NP battery

• Education– Proxy measure for cognitive reserve– Continuous variable• Highest level of years completed

MRI Acquisition

• 1.5 Tesla Siemens Magnatom Vision scanner– Within 1 week of NP testing– FLAIR pulse sequences– Field of view• 24 x 24 cm, matrix of 192 x 256 voxels

• Brain volume and SH volume calculated– Semi-automatic thresholding technique• Categorized bandwidths of light as white, black, or gray• Based on intensity histogram generated for each

individual

Brain Volume

• BV calculated– Summing all pixels classified as brain tissue– Ratio of SH• Total SH value in subcortical and PV areas over whole

BV• Calculated SH volumes

– Ration of total subcortical and PV hyperintensity over WBV, minus ventricular space

• Intra-rater reliability of SH quantification (>.96)

Analyses• Moderated multiple regression– Is relationship between MMSE score and SH volume

dependent on educational level (CR indicator)• Two regressions estimated– “Main Effects” model

• MMSE regressed onto mean centered SHV and mean centered education

– “Interaction” model• Added to see if relationship between SHV and MMSE

dependent on education level• SH volume and education level mean centered

before creation of interaction term

Results

• Regression of MMSE onto mean centered SH volume and mean centered education significant (F(2,33) = 5.77; p <.05)– 26% variance accounted– SH volume had negative relationship w/MMSE– Education had positive relationship w/MMSE

• Interaction accounted for additional 13% (R2 = .39) of variance (F(3,32) = 6.76; p < .05)– Modest effect size (f2 = .21)

Important Finding• Form of interaction model– See slopes of relationship between MMSE and SH

volume• High education (mean + 1 SD; ~ 15.4 years)• Low education (mean – 1 SD; ~ 7.6 years)

• Overall relationship between SH volume with MMSE scores is negative– Individuals with lower education that have high SH

volume, more likely to have lower MMSE– Individuals with higher education

• Relationship between SHV and MMSE is attenuated– Higher education better MMSE, despite > SH volume amounts

Discussion Points

• Education as proxy for CR provides protection against decline in cognitive function due to SH damage in brain

• Consistent with other studies– > SH volume = negative outcome on global

cognitive function in VaD patients

Main Hypotheses

• Protection of CR in VaD group supported– Those with higher education did better, despite

similar degrees of SH pathology• Implications– Mental activity in young adulthood are beneficial in

later life– Buffer (?) against functional decline (damage)– Potential means by which to modify risk factors– May be useful re: prognosis post dx– Protective effect of education

Other Work

• Higher premorbid ability < likely to develop VaD later

• WM disease = decreased speed of processing– Effect attenuated by higher education level– Worse with < education

Mechanism of CR

• Unknown, but– > Brain volume and head circumference may

provide buffer (synaptic connectivity)• Passive (brain reserve) model

– Role of individual variability in response to damage or compensation

• Active reserve model– Involved systems for task processing more efficient in those

with greater reserve» Redundancy

• Current study supports Active Reserve model

Limitations

• Study has pure VaD patients vs. mixed VaD– Not as likely in general clinical practice

• Small sample size– Interaction found, regardless

• Use of MMSE solely– Limited EF assessment (known to be affected in

VaD)– Still found effect

Final Points

• Greater education = greater ability to withstand damage found with VaD

• Need to encourage mental activity to decrease NP compromise with vascular pathology

• Education as a proxy (other proxies exist)• Prognosis affected by premorbid educational

level• Did not study role of higher SES or health

advantages found in more educated individuals

CE Question 1

Vascular dementia (VaD) is considered by some to be the most prevalent type of dementia in the United States, surpassing Alzheimer’s disease?

a. Trueb. False

CE Question 2

Subcortical hyperintensities (SH) represent a hallmark feature of subcortical vascular dementia?

a. Trueb. False

CE Question 3

In other dementia populations, such as AD, the level of cognitive impairment associated with neuropathological burden appears to be mitigated by higher educational attainment.

a. Trueb. False

CE Question 4

In this study, which statement is true?

a. Individuals with higher educational levels did better on the MMSE, despite greater SH amounts.b. Individuals with higher educational levels did worse on the MMSE, despite greater SH amounts.c. Neither a nor b is true.