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, 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 vascular disease – Sufficient to impact activities of daily living Possibly 2 nd most prevalent type of dementia in US (after Alzheimers 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 educations (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% (R 2 =.39) of variance (F(3,32) = 6.76; p <.05) – Modest effect size (f 2 =.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 Alzheimers disease? a.True b. False

CE Question 2 Subcortical hyperintensities (SH) represent a hallmark feature of subcortical vascular dementia? a.True b.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.True b.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.