Increased white matter hyperintensity in Alzheimer’s disease and frontotemporal dementia with behavioral variants

Increased white matter hyperintensities (WMH) are linked to the process of neurodegeneration and are common in patients with Alzheimer’s disease (AD) and patients with behavioral frontotemporal dementia (bvFTD), according to a 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 performed a comprehensive neuropsychological assessment and magnetic resonance imaging (MRI) and genetic screening for established risk variants for participants.

The patient cohorts did not differ in terms of baseline characteristics, comorbidities, or disease characteristics (all P> 0.05), with the exception of disease severity (P <0.001) and family history of neurodegenerative disease (P <0.001).

During Addenbrooke’s Cognitive Assessment (ACE) -III, patients with AD had poorer overall scores (P = 0.028), memory (P <0.001), and visual processing (P = 0.001), and better fluence (P) = 0.008) compared to patients with bvFTD.

Genetic assessment revealed that a minority of patients with AD and bvFTD had abnormalities in microtubule-associated protein tau (MAPT; 20% versus 4.5%), presenilin-1 (PSEN1; 20% versus 0%), and open chromosome 9 Frame 72 (C9orf72; 0% versus 17.5%) and granulin (GRN; 0% versus 9.1%).

Compared to controls, the patients had significantly larger WMH volumes (both P £ 0.001). Between patient cohorts, those with bvFTD had larger WMH volumes than those with AD (P <0.001). In patients with bvFTD, WMH volumes were not associated with mutation status (P = 0.71) or strong family history (P = 0.69).

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

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

This study did not validate vascular risk in patients and instead used a dichotomized measure that may have skewed these results.

The results showed that increased WMH was common in both diseases. The study’s authors concluded: “Our hypothesis that patients would have larger WMH volumes than controls was supported, with bvFTD continuing to have larger WMH volumes than AD 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 frontotemporal dementia and Alzheimer’s disease. Neurology. Published online on February 17, 2021 doi: 10.1212 / WNL.0000000000011638

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