Fibromyalgia and Risk of Alzheimer's DiseaseRelated Dementia: A Nationwide Bidirectional Case-Control Study

Background/Objectives: To evaluate the association between fibromyalgia and dementia, with emphasis on temporal directionality and Alzheimer's disease-related dementia. Methods: We conducted a nationwide, population-based matched case-control study including 9232 patients with fibromyalgia and 46,160 age- and sex-matched controls. Diagnoses in the Leumit Health Services database are recorded using a hybrid coding scheme that combines ICD-9-CM and WHO ICD-10 codes; the specific codes used to ascertain fibromyalgia and each dementia subtype are listed in the Methods. Outcomes were assessed within two predefined windows: up to 20 years before and up to 10 years after fibromyalgia diagnosis. Alzheimer disease-related dementia was defined as the primary outcome. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: During the 20 years preceding fibromyalgia diagnosis, no increased dementia prevalence was observed; Alzheimer disease-related dementia was less frequent among fibromyalgia patients (0.16% vs. 0.31%; absolute difference -0.15 percentage points; OR 0.52, 95% CI 0.31-0.89). In contrast, during the 10 years following diagnosis, fibromyalgia was associated with a higher prevalence of Alzheimer's disease-related dementia (1.43% vs. 0.99%; absolute difference +0.44 percentage points; OR 1.45, 95% CI 1.18-1.78). No consistent associations were found for other dementia subtypes, which should be interpreted as exploratory given low event counts. Conclusions: Fibromyalgia is associated with a higher prevalence of Alzheimer's disease-related dementia in the years following diagnosis, with no evidence of pre-diagnostic elevation. Although this temporal pattern argues against reverse causation, the prevalence-based design and residual confounding preclude causal inference. Fibromyalgia should be regarded as a potential risk marker for subsequent Alzheimer-related neurodegeneration rather than a demonstrated causal factor.