White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-β

Article type: Research Article

Authors: Freeze, Whitney M.^{a; b; *} | Jacobs, Heidi I. L.^a | Gronenschild, Ed H.^a | Jansen, Jacobus F. A.^b | Burgmans, Saartje^a | Aalten, Pauline^a | Clerx, Lies^a | Vos, Stephanie J.^a | van Buchem, Mark A.^c | Barkhof, Frederik^{d; e} | van der Flier, Wiesje M.^f | Verbeek, Marcel M.^g | Rikkert, Marcel Olde^h | Backes, Walter H.^b | Verhey, Frans R.^a | on behalf of the LeARN project

Affiliations: [a] Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, The Netherlands | [b] Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, School for Mental Health and Neuroscience, Maastricht, The Netherlands | [c] Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands | [d] Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands | [e] Institutes of Neurology and Healthcare Engineering, University College Lodon, London, UK | [f] Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands | [g] Departments of Neurology and Laboratory Medicine, Radboud University Medical Center Nijmegen, Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center, Nijmegen, The Netherlands | [h] Department of Geriatric Medicine, Radboud University Medical Center Nijmegen, Donders Institute for Brain, Cognition and Behaviour, and Radboud UMC, Alzheimer Center, Nijmegen, The Netherlands

Correspondence: [*] Correspondence to: Whitney M. Freeze, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, 6200MD Maastricht, The Netherlands. Tel.: +31 43 388 41 13; Fax: +31 43 388 40 92; E-mail: [email protected].

Abstract: Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer’s disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Aβ pathology was assessed as cerebrospinal fluid-derived Aβ1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Aβ on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Aβ and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Aβ and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Aβ42 levels, but not in individuals with normal CSF Aβ42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Aβ levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.

Keywords: Amyloid-beta, cerebral small vessel disease, dementia, neurodegeneration

DOI: 10.3233/JAD-160474

Journal: Journal of Alzheimer's Disease, vol. 55, no. 1, pp. 333-342, 2017