Food is a relatively undeveloped research subject in health and social welfare, particularly with respect to older people (Mennell et al. 1992), but some inroads have been made into understanding the specific neural substrates underlying abnormal eating behaviours for persons living with dementia.
It is probably fair to say that the dementia syndromes in which eating behaviours have been investigated the most include the dementia of Alzheimer type (at first signposted by problems in attention and new learning and memory, “DAT”), the behavioural variant frontotemporal dementia (at first signposted by problems in personality and behaviour, “bvFTD”), and temporal variants frontotemporal dementia (including problems in semantic knowledge, semantic dementia or “SD”).
First of all, it is important to appreciate that eating abnormalities are more likely in certain types of dementia more than others. For example, the frequencies of symptoms in all five domains, except swallowing problems, might be higher in the behavioural variant of frontotemporal dementia than in DAT (Ikeda et al., 2002); conversely, changes in food preference and eating habits were greater in SD than in DAT.
In semantic dementia, these authors found that the developmental pattern was very clear: a change in food preference developed initially, followed by appetite increase and altered eating habits, other oral behaviours, and finally swallowing problems. In bvFTD, the first symptom was altered eating habits or appetite increase. In Alzheimer’s disease, the pattern was not clear although swallowing problems developed in relatively early stages
Understanding which parts of the brain go wrong in producing these symptoms has turned out to be productive. Turning to the neuroanatomical implications of their findings, Ikeda and colleagues (Ikeda et al., 2002) have proposed that the changes in eating behaviours reflect the involvement of a common network in both variants of frontotemporal dementia—namely, the ventral (orbitobasal) frontal lobe, the temporal pole, and the amygdala (e.g. Cummings and Duchen, 1981).
The ventromedial frontal lobe is affected from an early stage in patients with bv-FTD and SD, ether by direct pathological involvement, or indirectly through damage to the temporal pole and amygdala, which are heavily interconnected with the ventromedial frontal lobe (Mummery et al., 2000).
The Kluver-Bucy syndrome has been known about by neurologists for some time, for its distinct cluster of symptoms. Bilateral degeneration of the amygdaloid nuclear complex in monkeys, and surgical removal of the temporal lobes in man, result in the Kluver–Bucy syndrome which is characterised by hyperorality, overeating, and the eating of quasi-food items (Bucy and Kluver, 1955; quoted in Ikeda et al., 2002).
The methodology of voxel-based morphometry has revolutionised our understanding of eating abnormalities in dementia. The aim of VBM is to identify differences in the local composition of brain tissue, while discounting large scale differences in gross anatomy and position.
This is achieved by spatially normalising all the structural images to the same stereotactic space, segmenting the normalised images into gray and white matter, smoothing the gray and white matter images and finally performing a statistical analysis to localize significant differences between two or more experimental groups.
The study by Howard Rosen and colleagues examined neuroanatomical correlates of behavioural abnormalities, as measured by the famous rating scale known as the ‘Neuropsychiatric Inventory’, in 148 patients with dementia using a brain imaging technique called voxel-based morphometry (Rosen et al., 2005). According to the authors, eating
behaviours did not uniquely associate with any specific brain region. The authors instead emphasized that eating behaviours in FTD are indeed complex and varied, and include carbohydrate craving, overeating with weight gain, obsessions for particular foods and occasionally oral exploration of nonfood objects, which may not always coexist in an individual patient (Miller et al., 1995).
Marked disturbances in eating behaviour, such as overeating and preference for sweet foods, are also commonly reported in bvFTD. And there has been for some time this might have something to do with a small area of the brainstem known as the “hypothalamus”.
The hypothalamus plays a critical role in feeding regulation, yet the relation between pathology in this region and eating behaviour in FTD is unknown.
The study by Piquet and colleagues (Piquet et al., 2011) identified significant atrophy of the hypothalamus in persons with bvFTD. Indeed, persons with prominent eating disturbance exhibited significant atrophy of the posterior hypothalamus. Features of eating disturbance, such as increased appetite, preference for sweet foods, and an increased tendency to eat the same foods, were present only in the bvFTD group, but were not observed in the healthy controls.
Taste and flavour are intimately enmeshed with one another. Deficits of flavour processing may be clinically important in FTD.
To examine flavour processing in FTD, Omar and colleagues (2012) studied flavour identification prospectively in 25 patients with FTD (12 with bvFTD, eight with semantic variant primary progressive aphasia (svPPA), five with non-fluent variant primary progressive aphasia (nfvPPA)) and 17 healthy control subjects, using a new test based on cross-modal matching of flavours to words and pictures (Omar et al., 2012).
Brain MRI volumes from the patient cohort were analysed using voxel-based morphometry to identify regional grey matter associations of flavour identification. Relative to the healthy control group, the bvFTD and svPPA subgroups showed significant deficits of flavour identification, and all three FTD subgroups showed deficits of odour identification.
Flavour identification performance in the combined FTD cohort was significantly associated with changes in distinct regions of the brain: grey matter volume in the left entorhinal cortex, hippocampus, parahippocampal gyrus and temporal pole. This profile, in fact, comprises brain substrates in the anteromedial temporal lobe which have been previously implicated in the associative processing of chemosensory stimuli (e.g. Gorno-Tempin et al., 2004).
Furthermore, in an interesting voxel-based morphometric study by Whitwell and colleagues, the authors found distinct neuroanatomical signatures of different abnormalities of eating behaviour (pathological sweet tooth and increased food consumption or hyperphagia) in individuals with frontotemporal lobar degeneration (FTD) (Whitwell et al., 2007).
In that study, sixteen male patients with FTD were assessed clinically.Volumetric brain magnetic resonance imaging was performed in all patients and in a group of nine healthy age-matched male controls and grey matter changes were assessed using an optimised VBM protocol.
Compared with healthy controls, the FTD group had a typical pattern of extensive bilateral grey matter loss predominantly involving the frontal and temporal lobes. Within the FTD group, grey matter changes associated with different abnormal behaviours were assessed. The development of pathological sweet tooth was associated with grey matter loss in a distributed brain network including bilateral posterolateral orbitofrontal cortex (Brodmann areas 12/47) and right anterior insula. Hyperphagia was associated with more focal grey matter loss in anterolateral orbitofrontal cortex bilaterally (Brodmann area 11).
Carers’ reports of changes in eating behaviour show that various forms of increased eating are commonly found at some stage in the course of dementia (Morris et al., 1989).
According to Keene and Hope (1998), Both studies showed that hyperphagia is a stable condition, generally occurring as a single episode. Duration of hyperphagia varied, ranging from 4 months to over 3 years in a few subjects. This is likely to be an underestimate as the end of the hyperphagia was often masked by the preventive measures taken by the carer.
Hyperphagia and associated eating changes occur frequently in DAT, and lead to considerable morbidity. However, the neurochemical basis for these neuropsychiatric behaviours is at present unclear. Medications known as selective serotonin reuptake inhibitors (SSRIs) have shown efficacy in the treatment of bulimia nervosa and binge eating disorders (Milano et al., 2005), as well as suppressing rebound hyperphagia in rats (Inoue et al., 1997).
Tsang and colleagues (2009) measured serotonin transporters, 5-HT1A, 5-HT2A, and 5-HT4 receptors using radioligand binding assays in the post-mortem temporal cortex of a cohort of controls and DAT patients longitudinally assessed for hyperphagia (Tsang et al., 2009). We found significant decreases in 5-HT4 receptor densities in the hyperphagic, but not normophagic, DAT group.
Intriguingly, Peter Nestor has described a virtual resolution of severe food and alcohol bingeing in anFTD patient using low-dose topiramate (Nestor, 2012). The prompt relapse on withdrawal and subsequent remission with reinstatement perhaps suggests that the improvement was causal and not coincidental to this behaviour abating as part of the natural evolution of the illness.
It will be interesting to work out whether the effect of topiramate is a primary one on eating behaviour, or part of a wider effect of topiramate on impulse control possibly involving serotonin somewhere (Pompanin et al., 2014).
It is clear that recent technological advances in neuroimaging have been able to shed much light on changes in eating behaviours in persons with dementia from different clinical diagnostic groups. In time, this might lead to suitable medications which might change these behaviours which can become difficult for some.
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