Increased White Matter Hyperintensity in Alzheimer Disease and Behavioral-Variant Frontotemporal Dementia

Investigators assessed white matter hypeintensity burden in patients with Alzheimer disease and behavioral-variant frontotemporal dementia.

Increased white matter hyperintensities (WMH) are associated with the process of neurodegeneration and are common among patients with Alzheimer disease (AD) and those with behavioral-variant frontotemporal dementia (bvFTD), according to study published in Neurology.

Patients with AD (n=65), with bvFTD (n=64), and healthy controls (n=66) were recruited at the Frontotemporal Dementia Research clinic in Australia between 2009 and 2016. Study researchers conducted comprehensive neuropsychological assessment, magnetic resonance imaging (MRI), and genetic screening for established risk variants for participants.

Patient cohorts did not differ for baseline characteristics, comorbidities, or disease characteristics (all P >.05) except for disease severity (P <.001) and family history of neurodegenerative disease (P <.001).

During Addenbrooke’s Cognitive Examination (ACE)-III, patients with AD performed poorer in total score (P =.028), memory (P <.001), and visuospatial processing (P =.001) evaluations and performed better in fluency (P =.008) compared with patients with bvFTD.

The genetic assessment indicated a minority of patients with AD and bvFTD had abnormalities in microtubule associated protein tau (MAPT; 20% vs 4.5%, respectively), presenilin-1 (PSEN1; 20% vs 0%, respectively), chromosome 9 open reading frame 72 (C9orf72; 0% vs 17.5%, respectively), and granulin (GRN; 0% vs 9.1% respectively).

Compared with controls, patients had significantly larger WMH volumes (both, P £.001). Between patient cohorts, those with bvFTD had larger WMH volumes than those with AD (P <.001). In patients with bvFTD, WMH volumes were not associated with mutational status (P =.71) or strong family history (P =.69).

Among patients with bvFTD, WMH was greater in anterior compared with posterior brain regions and larger lesions were located in the genu compared with the splenium of the corpus callosum. Among patients with AD, WMH was greater in posterior compared with anterior regions and larger lesions were located in the splenium of the corpus callosum.

In both patient groups, deficits in attention were associated with increased WMH in the bilateral splenium of the corpus callosum and superior corona radiata. Deficits in language were associated with WMH in the bilateral lingual gyri, and visuospatial impairments with WMH in the left parahippocampal gyrus and left frontal operculum.

This study did not validate vascular risk among patients, and instead used a dichotomized measure which may have biased these findings.

Results indicated that increased WMH was common in both diseases. The study authors concluded, “Our hypothesis that patients would show larger WMH volumes than controls was supported, with bvFTD further showing larger WMH volumes than AD…The larger WMH volumes observed in bvFTD compared to AD indicate greater pathological white matter change, which is consistent with previous findings of decreased tract integrity in bvFTD compared to AD.”


Huynh K, Piguet O, Kwok J, et al. Clinical and Biological Correlates of White Matter Hyperintensities in Patients with Behavioral-variant Frontotemporal Dementia and Alzheimer Disease. Neurology. Published online February 17, 2021 doi:10.1212/WNL.0000000000011638