White Matter Hyperintensities and Cognitive Dysfunction in Alzheimer Disease

Abstract

The effect of white matter lesions in magnetic resonance imaging or vascular atherosclerosis on cognitive function is not fully understood in Alzheimer disease (AD). In this investigation, we examined the influence of white matter lesions on cognitive decline in AD. A total of 142 patients with AD (44 men, mean age 65.7 + 7.6 years; mean education period 7.8 + 5.0 years) were included. Patients were divided into 4 groups based on the severities of white matter hyperintensities (WMH) in brain magnetic resonance images (MRI) using Fazekas scale. Cognitive functions were determined using the Korean version of the Mini-Mental State Examination (K-MMSE) and the Clinical Dementia Rating (CDR) scale before acetylcholinesterase inhibitors were administered. Of the 142 patients, 30% (43/142) had no white matter signal abnormality (grade 0). Fourteen percentage (20/142) were grade 1, 42% (59/142) grade 2, and 14% (20/142) were grade 3. Mean K-MMSE scores declined as MRI grades increased to grade 2 and 3 compared to grade 0 (P < .01). Clinical Dementia Ratings were also aggravated by MRI grade. These results remained significant after adjusting for compounding factors affecting cognitive functions; sex, age, number of years in full-time education, hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation. The presence of WMHs were associated with score of MMSE and CDR impairment in patients with AD. These features could be a correctable factor hastening cognitive decline in AD.

Keywords

Alzheimer disease white matter hyperintensities cognitive impairment

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References

Christiansen P. , Larsson HB , Thomsen C. , Wieslander SB , Henriksen O. Age dependent white matter lesions and brain volume changes in healthy volunteers. Acta Radiol. 1994;35(2):117-122.

Seshadri S. , Beiser A. , Selhub J. , et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346(7):476-483.

Honig LS , Kukull W. , Mayeux R. Atherosclerosis and AD: analysis of data from the US National Alzheimer’s Coordinating Center. Neurology. 2005;64(3):494-500.

Van den Heuvel DM , ten Dam VH , de Craen AJ , et al. Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population. J Neurol Neurosurg Psychiatry . 2006;77(2):149-153.

Akisaki T. , Sakurai T. , Takata T. , et al. Cognitive dysfunction associates with white matter hyperintensities and subcortical atrophy on magnetic resonance imaging of the elderly diabetes mellitus Japanese. Diabestes Metab Res Rev. 2006;22(5):376-384.

Darvesh S. , Freedman M. Subcortical dementia: a neuro-behavioral approach. Brain Cogn . 1996;31(2):230-249.

McKhann G. , Drachman D. , Folstein M. , Katzman R. , Price D. , Stadlan EM Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939-944.

Fazekas F. , Chawluk JB , Alavi A. , Hurtig HI , Zimmerman RA MR signal abnormalities at 1.5T in Alzheimer’s dementia and normal aging . AJR Am J Roentgenol. 1987;149(2):351-356.

Kang YW , Na DL , Hahn SH A validity study on the Korean Mini-Mental State Examination (K-MMSE) in dementia patients. J Korean Neurol Assoc. 1997;15(2):300-307.

10.

Choi SH , Na DL , Lee BH , et al. Estimating the Validity of the Korean Version of Expanded Clinical Dementia Rating (CDR) Scale. J Korean Neurol Assoc. 2001; 19(6):585-591.

11.

Shepherd J. A prospective study of pravastatin in the elderly at risk: new hope for older persons. Am J Geriatr Cardiol. 2004;13(3 suppl 1):17-24.

12.

Starr JM , Deary IJ , Inch S. , Cross S. , MacLennan WJ Age-associated cognitive decline in healthy old people. Age Ageing. 1997;26(4):295-300.

13.

Hughes CP , Berg L. , Danziger WL , Coben LA , Martin RL A new clinical scale for the staging of dementia. Br J Psychiatry . 1982;140:566-572.

14.

De Groot JC , de Leeuw F. -C, Oudkerk M. , et al. Cerebral white matter lesions and cognitive function: the Rotter-dam scan study. Ann Neurol . 2000;47(2):145-151.

15.

De Groot JC , de Leeuw FE , Oudkerk M. , et al. Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann Neur. 2002;52(3):335-341.

16.

Au R. , Massaro JM , Wolf PA , et al. Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study. Arch Neurol . 2006;63(2):246-250.

17.

Snowdon DA , Greiner LH , Mortimer JA , et al. Brain infarction and the clinical expression of Alzheimer disease . The Nun Study. JAMA. 1997;277(10):813-817.

18.

Bronge L. , Wahlund LO Prognostic significance of white matter changes in a memory clinic population . Psychiatry Res. 2003;122(3):199-206.

19.

Doddy RS , Massman PJ , Mawad M. , Nance M. Cognitive consequences of subcortical magnetic resonance imaging changes in Alzheimer’s disease: comparison to small vessel ischemic vascular dementia . Neuropsychiatry. Neuropsychol Behav Neurol. 1998;11(4):191-199.

20.

Modrego PJ , Rios C. , Perez Trullen JM , et al. The cerebrovascular pathology in Alzhimer’s disease and its influence on clinical variables. Am J Alzheimers Dis Other Demen. 2008;23(1):91-96.

21.

Skoog I. , Berg S. , Johansson B. , et al. The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year-olds. Acta neurol Scand. 1996;93(2-3):142-148.