Late-onset anorexia nervosa and Alzheimer’s disease: Could this case reflect a prodromal process?

Introduction

Anorexia nervosa (AN) typically emerges during adolescence or early adulthood, whereas late-onset cases are rare and often present with atypical clinical features [1]. The differential diagnosis including neurocognitive disorders and underlying neurodegenerative processes should be explored in late onset cases. Although behavioral and eating-related changes may occur during the prodromal phase of Alzheimer’s disease (AD)[2], the relationship between AN-like presentations and early AD pathology remains underexplored. This case examines a potential prodromal association between late-onset AN and AD-related biomarkers.

Case Presentation

A 59-year-old woman with no prior psychiatric history presented with a five-year history of progressive food restriction, self-induced vomiting, weight loss, and body image distortion had began during the COVID-19 pandemic following a short travel and stay in quarantine. Initially characterized by restrictive eating (baseline 85 kg) with diet, she developed postprandial vomiting due to fear of weight gain. Within one year, she lost approximately 35 kg; despite maintaining a normal BMI (21 kg/m²), restrictive behaviors and distorted body perception persisted. Her treatment history included selective serotonin reuptake inhibitors, mirtazapine, aripiprazole, and olanzapine, with limited clinical benefit. During the mental health examination, she appeared apathetic, was reluctant to participate in the interview, and gave short, single-word answers to questions. Her mood was depressed, and she had anxiety about her weight and body image, along with feelings of impoverishment. She reported subjective memory problems.

Due to late onset, absence of prior psychiatric history, cognitive complaints, and resistance to treatment, further evaluations were planned. Brain MRI showed mild age-consistent atrophy and microvascular changes without clear neurodegenerative findings. However, FDG-PET revealed hypometabolism in bilateral prefrontal, parietal, and temporal regions, more pronounced on the left, as well as in the left precuneus. Neuropsychological assessment demonstrated impairments in attention, executive functions, and learning. She was treated with fluvoxamine 200mg/day and olanzapine 2.5mg/day beside behavioral therapy. Behavioral interventions resulted in only partial and transient improvement and she was discharged with partial remission.

Following discharge, cerebrospinal fluid analysis performed in a neurology clinic showed decreased amyloid-beta 42 levels (518 pg/ml-reference:>1030), consistent with AD pathology. The patient was subsequently followed with a preliminary diagnosis of atypical Alzheimer’s disease.

Discussion

Late onset AN is uncommon and needs careful evaluation for secondary causes. Accumulating evidence suggests that neuropsychiatric and behavioral changes, including changes in eating behavior, may emerge during the prodromal stages of AD [2].

In this case, atypical features including late onset, absence of prior psychiatric history, apath, and poor treatment response are not characteristic of primary AN. Converging multimodal findings, including temporoparietal and precuneus hypometabolism on FDG-PET and reduced cerebrospinal fluid amyloid-beta 42 levels, support underlying AD pathology [3],[4]. Disruption of networks involved in self-referential processing and executive functioning may provide a neurobiological basis for body image disturbance, cognitive inflexibility, and persistent restrictive eating[5].

Although comorbidity cannot be excluded, this case suggests that AN-like presentations in late life may represent an atypical manifestation of neurodegeneration. These findings underscore the importance of considering underlying neurodegenerative processes in late onset, treatment-resistant psychiatric presentations accompanied by cognitive features.

References

1. Mangweth-Matzek, B., Kummer, KK., Hoek, HW., 2023. Update on the epidemiology and treatment of eating disorders among older people. Current Opinion in Psychiatry 36 (6), 405–411.
2. Polsinelli, AJ., Johnson, S., Crouch, A., Lane, KA., Pena-Garcia, A., Hammers, DB., Wang, S., Gao, S., Apostolova, LG., 2024. Neuropsychiatric symptom burden in early-onset and late-onset Alzheimer’s disease as a function of age. Alzheimer’s and Dementia 20 (8), 5481–5491.
3. Selkoe, D., Hardy, J., 2016. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Molecular Medicine 8, 595–608.
4. Isella, V., Crivellaro, C., Formenti, A., et al., 2022. Validity of cingulate–precuneus–temporo-parietal hypometabolism for single-subject diagnosis of biomarker-proven atypical variants of Alzheimer’s disease. Journal of Neurology 269, 4440–4451.
5. Gondo, M., Kawai, K., Moriguchi, Y., et al., 2023. Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study. PLOS ONE 18, e0283318.