Neural correlates of fat preference in frontotemporal dementia: translating insights from the obesity literature

Abstract

Objective: Alterations in eating behaviour are one of the diagnostic features of behavioural variant frontotemporal dementia (bvFTD). It is hypothesised that underlying brain network disturbances and atrophy to key structures may affect macronutrient preference in bvFTD. We aimed to establish whether a preference for dietary fat exists in bvFTD, its association with cognitive symptoms and the underlying neural mechanisms driving these changes. Methods: Using a test meal paradigm, adapted from the obesity literature, with variable fat content (low 20%, medium 40% and high 60%), preference for fat in 20 bvFTD was compared to 16 Alzheimer's disease (AD) and 13 control participants. MRI brain scans were analysed to determine the neural correlates of fat preference. Results: Behavioural variant FTD patients preferred the high-fat meal compared to both AD (U = 61.5; p = 0.001) and controls (U = 41.5; p = 0.001), with 85% of bvFTD participants consistently rating the high-fat content meal as their preferred option. This increased preference for the high-fat meal was associated with total behavioural change (Cambridge Behavioural Inventory: r s = 0.462; p = 0.001), as well as overall functional decline (Frontotemporal Dementia Rating Scale: r s = À0.420; p = 0.03). A preference for high-fat content in bvFTD was associated with atrophy in an extended brain network including frontopolar, anterior cingulate, insular cortices, putamen and amygdala extending into lateral temporal, posteromedial parietal and occipital cortices. Conclusions: Increased preference for fat content is associated with many of the canonical features of bvFTD. These findings offer new insights into markers of disease progression and pathogenesis, providing potential treatment targets.

Subjective Time in Dementia: A Critical Review

“…Such steeper delay discounting may manifest in the everyday life of bvFTD patients as the consumption of unhealthy but immediately rewarding foods, or a lack of other health-protective behaviours that incur an immediate cost but downstream benefit [ 176 ]. These findings resonate with patterns of behaviour common in bvFTD, such as dietary shifts in favour of calorie-dense or high-fat foods [ 177 ]. Time perception changes may also account for more subtle shifts in intertemporal decision-making in patient groups.…”

The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials

“…Disease progression in bvFTD has been associated with various behavioral changes, from an increase in core features, e.g., decreased socio-emotional abilities and increased multi-dimensional apathy, to specific changes, e.g., increased fat preference and hypersensitivity to loud noises ( Midorikawa et al, 2016 ; Wei et al, 2020 ; Ahmed et al, 2021 ; Foster et al, 2022 ), that correlate with FTD-specific progression measures (FTLD-CDR; FTD-FRS; atrophy rates). Alongside behavior, neuropsychiatric symptoms have been frequently reported, such as depression, anxiety, delusions and hallucinations ( Da Silva et al, 2021 ).…”

“…The neurotransmitter orexin A, known for regulation of various physiological functions (such as appetite and sleep), has been correlated with obsessive-compulsive (measured by SRI) and extrapyramidal symptoms, that may accompany disease progression (cross-sectional, N = 40) ( Roveta et al, 2022 ). Lastly, specific metabolic changes were found in bvFTD (compared to controls), such as altered metabolites in a wide range of pathways (including amino acids, energy and carbohydrate, cofactor and vitamin, lipid and nucleotide) and increased fat preference, offering a new field to reveal possible physiological progression markers ( N = 30, N = 20) ( Murley et al, 2020 ; Ahmed et al, 2021 ). However, for all suggested fluid biomarkers, e.g., NfL, sTREM2, GFAP, Orexin A as well as metabolic features, longitudinal observations are needed and highly recommended, before they can be evaluated in their potential to track disease progression.…”

Longitudinal volumetric changes in amygdala subregions in frontotemporal dementia

“…It is well established that patients with bvFTD exhibit a higher prevalence and greater severity of behavioral disturbances compared to patients with AD [ 52 ], and these disturbances are often associated with amygdala abnormalities. Some examples include emotion recognition deficits [ 53 , 54 ], reward deficits [ 55 ], and changes in eating behaviors [ 56 , 57 ]. This seemingly surprising similarity in amygdala atrophy profile between bvFTD and AD may suggest a complex interplay between the amygdala and other brain regions, such as the hippocampus and orbitofrontal cortex, which collectively underpin various cognitive and socio-emotional functions.…”