Advanced neuroimaging techniques may offer the potential to monitor disease progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative, multisystem disease that still lacks therapeutic outcome measures. We aim to investigate longitudinal functional and structural magnetic resonance imaging (MRI) changes in a cohort of patients with ALS monitored for one year after diagnosis.

Resting state functional MRI, diffusion tensor imaging (DTI), and voxel-based morphometry analyses were performed in 22 patients with ALS examined by six-monthly MRI scans over one year.

During the follow-up period, patients with ALS showed reduced functional connectivity only in some extramotor areas, such as the middle temporal gyrus in the left frontoparietal network after six months and in the left middle frontal gyrus in the default mode network after one year without showing longitudinal changes of cognitive functions. Moreover, after six months, we reported in the ALS group a decreased fractional anisotropy (P = .003, Bonferroni corrected) in the right uncinate fasciculus. Conversely, we did not reveal significant longitudinal changes of functional connectivity in the sensorimotor network, as well as of gray matter (GM) atrophy or of DTI metrics in motor areas, although clinical measures of motor disability showed significant decline throughout the three time points.

Our findings highlighted that progressive impairment of extramotor frontotemporal networks may precede the appearance of executive and language dysfunctions and GM changes in ALS. Functional connectivity changes in cognitive resting state networks might represent candidate radiological markers of disease progression.

Frontotemporal degeneration (FTD) dementia often begins before age 60 and predominantly presents as four subtypes with prominent features of language, behavior, cognition, and motor symptoms. The early onset and unique symptoms place a distinct burden on caregivers of individuals with FTD versus other dementia types, such as Alzheimer’s disease. This is the first known study to examine the domains of the FTD caregiver burden and the caregiver and patient characteristics associated with these domains.

In 2017, 674 FTD caregivers in the United States (US) completed a web-based survey of caregiver and patient demographics, disease severity/symptoms, caregiver burden, and financial costs of caregiving. The major factors of caregiver burden (Zarit Burden Inventory) were determined using a principal axis factor analysis with varimax rotation. Multiple linear regression analyses examined caregiver and patient characteristics associated with overall burden and three major factors of burden: role strain, personal strain, and performance strain.

Increased neuropsychiatric symptoms was associated with overall caregiver burden and greater role, personal, and performance strain. Younger caregivers experienced greater overall burden and performance strain, female caregivers experienced increased role strain, and male caregivers experienced greater performance strain. Financial costs of caregiving and experiencing a caregiving crisis in the past year were associated with higher overall burden and role strain.

This study suggests that the severity and sources of burden differ for caregivers of FTD patients versus patients with other dementia types. Differing predictors for each burden domain suggest targeted interventions to address the unique FTD caregiving challenges.