A new study revealed that itching of undetermined origin is significantly more common in patients with frontotemporal lobar degeneration spectrum disorders compared to those with Alzheimer's disease. The research also identified specific brain regions associated with this condition in patients.
Methods
The study, published in JAMA Neurology, evaluated data and brain magnetic resonance images (MRIs) from participants with frontotemporal lobar degeneration spectrum disorders or Alzheimer's disease treated at the University of California, San Francisco, Memory and Aging Center between May 1, 2002, and December 31, 2021.
Participants underwent structural brain MRI within 6 months of initial diagnosis. Research visit summaries were reviewed to validate qualitative details and accurately identify itching of undetermined origin. Researchers reviewed 2,091 research visit summaries for 1,112 patients exhibiting symptoms of frontotemporal lobar degeneration spectrum disorders or Alzheimer's disease.
The study included 454 participants: 137 in the itching group (mean age = 62.7 years, 54% female) and 317 in the non-itching group (mean age = 60.7 years, 49% female). Groups were similar in age, sex, and disease severity.
Results
Researchers found that 38% of patients with frontotemporal lobar degeneration spectrum disorders (95/248) experienced itching of undetermined origin, compared to only 18% of patients with Alzheimer's disease (14/77). The odds of experiencing itching were 2.4 times higher for patients with frontotemporal lobar degeneration spectrum disorders compared to all other dementia cases.
Behavioral variant frontotemporal dementia was the most common subtype associated with itching, accounting for 46% (44/95) of cases with itching of undetermined origin.
Subgroup Analysis
For further neuroimaging analysis, 43 patients in the itching group and 227 in the non-itching group had available structural brain MRIs. The researchers formed a non-itching subgroup matched 2:1 to the itching group by age, disease severity, and diagnosis, resulting in 86 individuals in the non-itching group.
Image processing was performed using the Computational Anatomy Toolbox in SPM12. Voxel-based morphometry analysis compared gray matter volume loss between groups within preselected regions of interest associated with itching and scratching behaviors.
After excluding cases with MRI artifacts or excessive motion, the final imaging analysis included 37 individuals in the itching group and 77 in the non-itching group. A group of 75 healthy controls was also selected for comparison.
Neuroimaging analysis revealed that patients with itching of undetermined origin exhibited greater gray matter atrophy in several brain regions compared to healthy controls:
- Bilateral: amygdala, insula, precentral gyrus, and cingulum
- Right hemisphere: frontal superior gyrus and thalamus.
When comparing behavioral variant frontotemporal dementia patients with and without itching, those with itching showed right-lateralized gray matter atrophy affecting the insula, thalamus, superior frontal gyrus, and cingulum.
The researchers suggested that dysfunction in the right anterior insula and its connected regions may contribute to dysregulation of itching-scratching networks in patients with frontotemporal lobar degeneration spectrum disorders, resulting in uncontrollable itching or skin picking.
Conclusions
The study found that itching of undetermined origin was present in approximately one in three participants with frontotemporal lobar degeneration spectrum disorders and one in two patients with behavioral variant frontotemporal dementia. In contrast, only one in six patients with Alzheimer's disease experienced this condition.
Qualitative descriptions of itching revealed that it was often repetitive, stereotyped, and compulsive in nature. Itching was typically localized to the face, eyes, back, fingernails, arms, or legs. Many patients were unable to voluntarily cease itching, resulting in injuries such as scars.
A neuroimaging subanalysis showed that compared to healthy controls, the group with itching exhibited greater gray matter atrophy bilaterally in the amygdala, insula, precentral gyrus, and cingulum, as well as in the right frontal superior gyrus and thalamus.
When comparing patients with behavioral variant frontotemporal dementia who did and did not experience itching, those with itching showed right-lateralized gray matter atrophy affecting the insula, thalamus, superior frontal gyrus, and cingulum.
The researchers concluded that in frontotemporal lobar degeneration spectrum disorders, as well as dysfunction in the right anterior insula and its connected regions, may contribute to dysregulation of itching-scratching networks, resulting in uncontrollable itching or skin picking.
Complete ethics declarations are available within the study.