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ARTICLES: K. Smith, L. Flicker, N. T. Lautenschlager, O. P. Almeida, D. Atkinson, A. Dwyer, and D. LoGiudice High prevalence of dementia and cognitive impairment in Indigenous Australians Neurology 2008; 71: 1470-1473 [Abstract] [Full text] [PDF]

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High prevalence of dementia and cognitive impairment in Indigenous Australians

Jannis Kountouras, Emmanuel Gavalas, Marina Boziki, Christos Zavos, Georgia Deretzi, Nikolaos Grigoriadis, Eleni Tsiaousi, Panagiotis Katsinelos, Dimitrios Chatzopoulos, Dimitrios Tzilves, Georgios Kouklakis   (16 January 2009)

Reply from the authors

Kate Smith, Leon Flicker, Nicola Lautenschlager, Osvaldo Almeida, David Atkinson and Dina LoGiudice   (16 January 2009)

High prevalence of dementia and cognitive impairment in Indigenous Australians 16 January 2009
Jannis Kountouras, Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, GREECE, Emmanuel Gavalas, Marina Boziki, Christos Zavos, Georgia Deretzi, Nikolaos Grigoriadis, Eleni Tsiaousi, Panagiotis Katsinelos, Dimitrios Chatzopoulos, Dimitrios Tzilves, Georgios Kouklakis Send Correspondence to journal: Re: High prevalence of dementia and cognitive impairment in Indigenous Australians jannis{at}med.auth.gr Jannis Kountouras, et al.	We read with interest the paper by Smith et al. who concluded that the prevalence of dementia and cognitive impairment is substantially higher among indigenous than in non-indigenous Australians. [1] The background prevalence of Helicobacter pylori (Hp) urea breath test positivity in indigenous Australians is 76%; the prevalence in the remote rural community is 91% compared to 60% in the urban community. [2] Although degenerative diseases including dementia and cognitive impairment have an increasingly high impact in the aged population, their association with Hp infection (Hp-I) has only recently been addressed. [3,4] A relationship between dementia and Hp-I appears to exist based on comparable data. To clarify, both diseases mainly affect old people in the developed world and Hp-I has been implicated in a variety of extra-digestive vascular conditions including functional vascular disorders, hypertension, atherosclerosis, ischemic heart and cerebrovascular disorders. These also appear to be risk factors for dementia, mainly by impairing blood-brain barrier, a common denominator associated with dementia including Alzheimer disease (AD). These conditions contribute to the clinical manifestations and worsening of AD. [5] In the nervous system, Hp-I may be associated with autoimmune sequelae development observed in peripheral neuropathies and AD. [5] We have documented a high prevalence of Hp-I in Greek patients with AD establishing a significant relationship between Hp-I and AD confirmed by histology. [3] In a subsequent study, we found a high prevalence of Hp-I in Greek patients with mild cognitive impairment. [4] We also found an increased Hp-specific IgG antibody level in the cerebrospinal fluid of AD patients and this titer correlated with the degree of disease severity. It would be interesting to know if Smith et al. considered comparable data in their indigenous Australian participants who would be expected to present with high Hp-I prevalence. [1] Such data may be important considering the many ways that Hp-I could influence the pathophysiology of dementia. Specifically, Hp-I promotes arteriosclerosis through induction of platelet-leukocyte aggregation, via autoimmune processes against endothelial cells, or by increased homocysteine blood levels due to decreased folic acid and cobalamin. It also produces reactive oxygen metabolites participating in neuronal oxidative damage loss. Further pathogenetic mechanisms include conversion of fibrinogen into fibrin, induction of molecular mimicry by the saccharide part of lipopolysaccharides of Hp with host antigens, release of proinflammatory and vasoactive agents, and induction of apoptotic processes. [5] References 1. Smith K, Flicher L, Lautenschlager NT, et al. High prevalence of dementia and cognitive impairment in Indigenous Australians. Neurology 2008;71:1470-1473. 2. Windsor HM, Abioye-Huteyi EA, Leber JM, Morrow SD, Bulsara MK, Marshall BJ. Prevalence of Helicobacter pylori in Indigenous Western Australians: comparison between urban and remote rural populations. Med J Aust 2005;182:210-213. 3. Kountouras J, Tsolaki M, Gavalas E, et al. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 2006;66:938-940. 4. Kountouras J, Tsolaki M, Boziki M, et al. Association between Helicobacter pylori infection and mild cognitive impairment. Eur J Neurol 2007;14:976-982. 5. Kountouras J, Gavalas E, Zavos C et al. Alzheimer's disease and Helicobacter pylori infection: defective immune regulation and apoptosis as proposed common links. Med Hypotheses 2007;68:378-388. Disclosure: The authors report no disclosures.
Reply from the authors 16 January 2009
Kate Smith, West Australian Centre for Health and Ageing University of Western Australia, Royal Perth Hospital, Box X2213, Perth, WA Australia 6001, Leon Flicker, Nicola Lautenschlager, Osvaldo Almeida, David Atkinson and Dina LoGiudice Send Correspondence to journal: Re: Reply from the authors kate.smith{at}uwa.edu.au Kate Smith, et al.	We thank Dr. Kountouras and colleagues for their interest in our article. [1] We did not test for Helicobacter pylori infection (Hp-I) during our study yet we recognize that Hp-I is prevalent in indigenous Australians. [2] There are a number of plausible explanations for an association between and cognitive impairment but not all imply causality. Dr. Kountouras et al. consider possible mechanisms by which Hp-I may be a contributing factor to dementia and cognitive impairment. Based on current knowledge, such a relationship cannot be excluded. One theory is that the effect of atrophic gastritis (caused by the infection) on levels of vitamin B-12, folate—and thus homocysteine—may increase the risk of cognitive impairment through vascular disorders. [3] Others have demonstrated that folate and B-12 nutritional deficiency and elevated homocysteine levels in indigenous Australians [6] and diminished levels of vitamin B-12 and elevated homocysteine have been associated with cognitive impairment. [7] Although it was not one of our research objectives, the association between the high prevalence of Hp-I and dementia in indigenous Australians is intriguing and requires further investigation. References 6. Shaw JT, McWhinney B, Tate J R, et al. Plasma homocysteine levels in Indigenous Australians. Med J Aust 1999;170:19-22. 7. Flicker L, Martins RN, Thomas J, et al. Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men. Journal of Alzheimer's Disease 2004;6:329-336. Disclosure: The authors report no disclosures.