Background: Medial temporal atrophy (MTA) is a recognized marker of Alzheimer’s disease (AD), and white matter hyperintensities (WMH) are frequently observed on MRI of AD. The purpose of this study was to understand the role of WMH in MTA. Methods: Subjects were 94 probable AD patients and 51 cognitively normal subjects. WMH was assessed based on the severity of deep WMH (DWMH) and periventricular WMH (PWMH). Each structural volume was evaluated using the Individual Brain Atlases from the Statistical Parametric Mapping Toolbox. Results: There were no significant differences between subjects with and without WMH in terms of general cognitive function scales. Subjects with AD with WMH had decreased volume in the bilateral orbital frontal gyrus, frontal rectus gyrus, and olfactory gyrus, but not in the medial temporal lobes. After correcting for differences in DWMH, age and Clinical Dementia Rating Scale (CDR), AD with PWMH showed decreased volumes in the bilateral hippocampi. AD with PWMH showed worse scores on the Clinical Dementia Rating-Sum of Boxes and Barthel-ADL, and some frontal executive function tests. Those with DWMH did not show any reductions in the medial temporal lobes. Conclusion: WMH in AD is not associated with medial temporal lobe atrophy, but PWMH is independently correlated with hippocampal volume reduction.

1.
Calvini P, Chincarini A, Gemme G, et al: Automatic analysis of medial temporal lobe atrophy from structural MRIs for the early assessment of Alzheimer disease. Med Phys 2009;36:3737–3747.
2.
Shim YS, Youn YC, Na DL, et al: Effects of medial temporal atrophy and white matter hyperintensities on the cognitive functions in patients with Alzheimer’s disease. Eur Neurol 2011;66:75–82.
3.
Blasko I, Jellinger K, Kemmler G, et al: Conversion from cognitive health to mild cognitive impairment and Alzheimer’s disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine. Neurobiol Aging 2008;29:1–11.
4.
Apostolova LG, Dinov ID, Dutton RA, et al: 3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer’s disease. Brain 2006;129:2867–2873.
5.
Sabuncu MR, Desikan RS, Sepulcre J, et al: The dynamics of cortical and hippocampal atrophy in Alzheimer disease. Arch Neurol 2011;68:1040–1048.
6.
Apostolova LG, Green AE, Babakchanian S, et al: Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer disease. Alzheimer Dis Assoc Disord 2012;26:17–27.
7.
Kerchner GA, Hess CP, Hammond-Rosenbluth KE, et al: Hippocampal CA1 apical neuropil atrophy in mild Alzheimer disease visualized with 7-T MRI. Neurology 2010;75:1381–1387.
8.
Bocti C, Swartz RH, Gao FQ, Sahlas DJ, Behl P, Black SE: A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia. Stroke 2005;36:2126–2131.
9.
van Dijk EJ, Prins ND, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM: Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan Study. Stroke 2008;39:2712–2719.
10.
Ku BD, Na DL, Moon SY, et al: Neuropsychological correlates of the proportional impact of white matter hyperintensities on mild to moderate dementia: The MRI 300 study. Dement Geriatr Cogn Disord 2011;31:397–405.
11.
van der Flier WM, Middelkoop HA, Weverling-Rijnsburger AW, et al: Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD. Neurology 2004;62:1862–1864.
12.
Oosterman JM, Vogels RL, van Harten B, et al: The role of white matter hyperintensities and medial temporal lobe atrophy in age-related executive dysfunctioning. Brain Cogn 2008;68:128–133.
13.
Taki Y, Kinomura S, Sato K, et al: Correlation between degree of white matter hyperintensities and global gray matter volume decline rate. Neuroradiology 2011;53:397–403.
14.
Appel J, Potter E, Bhatia N, et al: Association of white matter hyperintensity measurements on brain MR imaging with cognitive status, medial temporal atrophy, and cardiovascular risk factors. AJNR Am J Neuroradiol 2009;30:1870–1876.
15.
Seo SW, Ahn J, Yoon U, et al: Cortical thinning in vascular mild cognitive impairment and vascular dementia of subcortical type. J Neuroimaging 2010;20:37–45.
16.
Sachdev PS, Chen X, Joscelyne A, Wen W, Altendorf A, Brodaty H: Hippocampal size and dementia in stroke patients: The Sydney Stroke Study. J Neurol Sci 2007;260:71–77.
17.
Du AT, Schuff N, Chao LL, et al: White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy. Neurobiol Aging 2005;26:553–559.
18.
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;15:300–308.
19.
Hogervorst E, Combrinck M, Lapuerta P, Rue J, Swales K, Budge M: The Hopkins verbal learning test and screening for dementia. Dement Geriatr Cogn Disord 2002;13:13–20.
20.
Kang YW, Na DL, Hahn SH (eds): Seoul Neuropsychological Screening Battery. Incheon, Human Brain Research & Consulting Co, 2003.
21.
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;34:939–944.
22.
Yang DW, Cho BL, Chey JY, Kim SY, Kim BS: The development and validation of korean dementia screening questionnaire (kdsq). J Korean Neurol Assoc 2002;20:135–141.
23.
Son SJ, Lee KS, Na DL, et al: The effect of anemia and white matter hyperintensities (wmh) on cognitive impairment in patients with amnestic mild cognitive impairment (mci). Arch Gerontol Geriatr 2012;55:251–256.
24.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA: MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 1987;149:351–356.
25.
Scheltens P, Barkhof F, Leys D, et al: A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci 1993;114:7–12.
26.
Heo JH, Lee ST, Kon C, Park HJ, Shim JY, Kim M: White matter hyperintensities and cognitive dysfunction in alzheimer disease. J Geriatr Psychiatry Neurol 2009;22:207–212.
27.
Moon SY, Na DL, Seo SW, et al: Impact of white matter changes on activities of daily living in mild to moderate dementia. Eur Neurol 2011;65:223–230.
28.
Bigler ED, Kerr B, Victoroff J, Tate DF, Breitner JC: White matter lesions, quantitative magnetic resonance imaging, and dementia. Alzheimer Dis Assoc Disord 2002;16:161–170.
29.
Kee Hyung P, Lee JY, Na DL, et al: Different associations of periventricular and deep white matter lesions with cognition, neuropsychiatric symptoms, and daily activities in dementia. J Geriatr Psychiatry Neurol 2011;24:84–90.
30.
Selden NR, Gitelman DR, Salamon-Murayama N, Parrish TB, Mesulam MM: Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 1998;121:2249–2257.
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