Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case–control study

Departments of Neurology, Erasmus Medical Centre Rotterdam, Rotterdam, Netherlands.
Journal of Neurology Neurosurgery & Psychiatry (Impact Factor: 6.81). 12/2003; 74(11):1574-6.
Source: PubMed


A retrospective case-control study was carried out on 80 patients with sporadic frontotemporal dementia and 124 age, sex, and surrogate informant matched controls with respect to various medical and environmental risk factors. Head trauma was associated with an odds ratio of 3.3 (95% confidence interval (CI), 1.3 to 8.1). Although recall bias may play a role, the frontal lobes are known to be especially vulnerable to even mild head trauma. Thyroid disease was associated with a 2.5 times increased risk of frontotemporal dementia (95% CI, 0.9 to 7.9), which was not statistically significant (p = 0.09) owing to limited power. As altered thyroid hormone status has been observed before in frontotemporal dementia, future studies will be important to confirm this observation.

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    • "This is a very significant finding in our population whereas in Latin America, diabetes is a highly prevalent disease in over 45 years, with higher percentages of cases than the rest of the world [20]. In two previous retrospective case–control studies the prevalence of this antecedent was higher in patients with FTD, but the multivariate analysis showed there were no statistically significant differences [5,21]. The explanation for this association remains unclear, but several findings from clinical and experimental research encourage the formulation of hypotheses about the underlying mechanisms. "
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    ABSTRACT: Cardiovascular risk factors (CRF) were widely described as related to dementia. There are very few studies regarding this association in FTD. The objective of the study was to compare the frequency of CRF in our population with FTD and controls. 100 consecutive subjects with FTD diagnosis according to Lund-Manchester clinical criteria and 200 controls matched by age and sex were included between January 2003 to February 2007 at the Cognitive and Behavior Unit of Hospital Italiano de Buenos Aires. Clinical evaluation, laboratory tests, brain images (CT/MRI), neuropsychological and neuropsychiatric assessment were performed. Multiple regression analysis was performed to analyze the association in CRF between FTD patients vs. controls. The mean age in FTD was 69.7 ± 0.9 vs. 70.1 ± 0.8 in controls (p 0.12). No difference in gender was observed between cases and controls. No differences were identified between patients and controls regarding hypertension (HTA) (65% vs. 67,3% p 0.44); dyslipidemia (57% vs. 54.7% p 0.74); obesity (39% vs. 27.6% p 0.14) and hypothyroidism (26% vs. 17.1% p 0.1). A significant difference was observed for Diabetes Mellitus (39% vs. 22.6% p 0.001). In our population, Diabetes Mellitus was associated as an independent risk factor for FTD. To our knowledge this is the first report in which CRF were evaluated prospectively in FTD patients. More studies are needed to confirm this finding in larger populations.
    Translational Neurodegeneration 06/2014; 3(1):13. DOI:10.1186/2047-9158-3-13
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    • "Up to now, autosomal dominant pattern of inheritance has been reported in all the identified causative genetic variations, even if a few studies suggested a number of modifier genetic risk factors influencing disease onset and clinical presentation [6] [8] [9]. It has to be still established whether other genetic determinants are involved or whether environmental factors might play a role in disease pathogenesis [10]. Discovery of causative genes has allowed a giant step forward in the knowledge of genetic bases of FTD; several studies conducted by cutting-edge technologies to dissect possible genetic-driven pathogenesis in still unclassified cases are ongoing. "
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    ABSTRACT: Frontotemporal dementia (FTD) has a strong genetic basis, with familial forms occurring in 30-50% of cases. Causative genes have been identified, with an autosomal dominant pattern of inheritance. Notwithstanding, in a number of cases with positive family history no pathogenetic mutation has been reported, and the role of genetics in sporadic cases is still unclear. The aim of the present study was to estimate the genetic contribution to FTD using concordance among parent-offspring pairs. Heritability of early-onset (EO, <65 years) and late-onset (LO, ≥65 years) FTD was estimated by examining the concordance between parents and offspring. Probands with at least one parent whose dementia status was known were recruited from 15 Italian centers, and the presence or absence of dementia was considered in siblings. Different prevalence estimates, as available by literature data, were tested. A total of 260 probands and 1619 family members were considered in this study. We found that parent-offspring concordance in FTD was 6.25%, resulting in hereditability of 98.5% (95% confidence interval (CI): 85.0%-100.0%). Equal heritability for both sexes regardless of parental gender was reported. EO-FTD showed hereditability of 86.3% (95% CI: 77.0%-95.0%) and LO-FTD of 75.7% (95% CI: 65.0%-86.0%). Estimating the contribution of genetics in FTD may help in driving future genetic studies to identify new pathogenetic determinants. We suggest that in most of the cases FTD is a genetic-based disease, even in the elderly. Different inheritance modality might be considered in future work, beyond autosomal dominant disease.
    Journal of Alzheimer's disease: JAD 05/2013; 41(2). DOI:10.3233/JAD-130128 · 4.15 Impact Factor
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    • "They are estimated to affect 400,000 Americans younger than 65 years of age (Maslow, 2006), making it as prevalent as AD in this age group. Furthermore, recent evidence suggests that FTDs are frequent also in older populations (Ratnavalli et al., 2002; Rosso et al., 2003). "
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    ABSTRACT: The most frequent neurodegenerative diseases (NDs) are Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal lobar degeneration associated with protein TDP-43 (FTLD-TDP). Neuropathologically, NDs are characterized by abnormal intracellular and extra-cellular protein deposits and by disease-specific neuronal death. Practically all terminal stages of NDs are clinically associated with dementia. Therefore, major attention was directed to protein deposits and neuron loss in supratentorial (telencephalic) brain regions in the course of NDs. This was also true for PD, although the pathological hallmark of PD is degeneration of pigmented neurons of the brainstem's substantia nigra (SN). However, PD pathophysiology was explained by dopamine depletion in the telencephalic basal ganglia due to insufficiency and degeneration of the projection neurons located in SN. In a similar line of argumentation AD- and FTLD-related clinical deficits were exclusively explained by supratentorial allo- and neo-cortical laminar neuronal necrosis. Recent comprehensive studies in AD and PD early stages found considerable and unexpected involvement of brainstem nuclei, which could have the potential to profoundly change our present concepts on origin, spread, and early clinical diagnosis of these diseases. In contrast with PD and AD, few studies addressed brainstem involvement in the course of the different types of FTLD-TDP. Some of the results, including ours, disclosed a higher and more widespread pathology than anticipated. The present review will focus mainly on the impact of brainstem changes during the course of the most frequent NDs including PD, AD, and FTLD-TDP, with special emphasis on the need for more comprehensive research on FTLDs.
    Frontiers in Neurology 07/2011; 2:42. DOI:10.3389/fneur.2011.00042
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