Impact of Strategically Located White Matter Hyperintensities on Cognition in Memory Clinic Patients with Small Vessel Disease.
OBJECTIVE
Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD.


METHODS
A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory.


RESULTS
Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume.


CONCLUSIONS
Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs.
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
J Matthijs
JM
Biesbroek
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Nick A
NA
Weaver
Memory Aging & Cognition Centre, National University Health System, Singapore, Singapore.|Department of Pharmacology, National University of Singapore, Singapore, Singapore.
Saima
S
Hilal
Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands.
Hugo J
HJ
Kuijf
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.|Memory Aging & Cognition Centre, National University Health System, Singapore, Singapore.|Academic Medicine Research Institute, Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore.
Mohammad Kamran
MK
Ikram
Memory Aging & Cognition Centre, National University Health System, Singapore, Singapore.|Department of Pharmacology, National University of Singapore, Singapore, Singapore.
Xin
X
Xu
St. Luke's Hospital, Singapore, Singapore.
Boon Yeow
BY
Tan
Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
Narayanaswamy
N
Venketasubramanian
Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, the Netherlands.
Albert
A
Postma
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Geert Jan
GJ
Biessels
Memory Aging & Cognition Centre, National University Health System, Singapore, Singapore.|Department of Pharmacology, National University of Singapore, Singapore, Singapore.
Christopher P L H
CP
Chen
D000368:Aged; D020643:Anterior Thalamic Nuclei / Q000473:pathology; D059345:Cerebral Small Vessel Diseases / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000473:pathology*; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*