Showing posts with label dementia. Show all posts
Showing posts with label dementia. Show all posts

Monday, 11 September 2017

On drinking water lithium content and dementia risk

"Lithium in tap water may cut dementia" went the BBC website headline reporting the study results published by Lars Vedel Kessing and colleagues [1]. The authors relied on some of those oh-so important Scandinavian population registries and other data to examine a possible connection between drinking water lithium levels and risk of "diagnosis of dementia in a hospital inpatient or outpatient contact."

Alongside looking at data for some 70,000 people diagnosed with dementia and nearly three-quarters of a million non-diagnosed controls, researchers estimated lithium exposure via drinking water based on data from over 150 waterworks. The relationship they observed between lithium in drinking water and risk of dementia diagnosis was not altogether straight-forward as "higher long-term lithium exposure from drinking water may be associated with a lower incidence of dementia" but the relationship was described as "nonlinear." Nonlinear meant that those with drinking water levels of lithium at moderate levels - between 5.1 and 10 micrograms per litre - actually showed an increased risk of dementia compared to those who had low levels of lithium (below 5 micrograms per litre) in their drinking water. The authors add: "Nonlinear dose-response associations are often found in medicine, with a gradual increase in drug response at the lower doses and gradual leveling off in response at the highest doses."

The authors do caution about their results and the various limitations attached to the findings. Not least is their reliance on a diagnosis of dementia as a starting point and how factors such as "accessibility to health care services that vary geographically" may have influenced such results. Indeed they note: "accessibility to health care services is increased in eastern regions of Denmark, where lithium levels generally are higher, and decreased in western regions, specifically in Jutland, where lithium levels generally are lower." They also found: "a direct inverse association with increasing risk of dementia in rural areas" as part of a sensitivity analysis, and as noted in some other studies [2]. More investigation is definitely required.

But these remain interesting results. Lithium is a treatment of choice when it comes to conditions such as bipolar disorder (see here). I've also talked about this stuff in connection to some other important research looking at suicide reduction too (see here) based on quite a body of research [3] (and growing all the time [4]) but minus simplifying something like suicide ideation, attempts or completion all down to lithium 'deficiency'. In relation to the possible effects on dementia risk, this is not the first time that lithium has been discussed as per findings looking at dementia risk in cases of lithium treated bipolar disorder [5] (something else that has been discussed on this blog - see here).

Questions still however remain. The mechanism of effect(s) is still to be suitably deciphered and one also needs to keep in mind the safety profile of lithium [6] as a balance to any risk-reduction effects on dementia or anything else. This is particularly relevant to those who might be at particular risk for dementia [7]. I'll also add that any focus on lithium intake and dementia also needs to keep in mind other *associations* that have been previously discussed in the peer-reviewed research literature such as that talking about vitamin D deficiency and dementia risk for example (see here) as part of a wider research interest in vitamin D and cognitive functions in the context of ageing (see here).

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[1] Kessing LV. et al. Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry. 2017 Aug 23.

[2] Contador I. et al. Childhood and Adulthood Rural Residence Increases the Risk of Dementia: NEDICES Study. Curr Alzheimer Res. 2015;12(4):350-7.

[3] Cipriani A. et al. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013 Jun 27;346:f3646.

[4] Kanehisa M. et al. Serum lithium levels and suicide attempts: a case-controlled comparison in lithium therapy-naive individuals. Psychopharmacology (Berl). 2017 Aug 28.

[5] Gerhard T. et al. Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study. Br J Psychiatry. 2015 Jul;207(1):46-51.

[6] Albert U. et al. Lithium treatment and potential long-term side effects: a systematic review of the literature. Riv Psichiatr. 2014 Jan-Feb;49(1):12-21.

[7] Holroyd S. & Rabins PV. A Retrospective Chart Review of Lithium Side Effects in a Geriatric Outpatient Population. Am J Geriatr Psychiatry. 1994 Autumn;2(4):346-351.

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Tuesday, 11 July 2017

Dementia risk in adult ADHD

"Adults with ADHD [attention-deficit hyperactivity disorder] have a 3.4-fold risk of developing dementia."

That was the conclusion reached by Nian-Sheng Tzeng and colleagues [1] who applied the 'big data' power of the Taiwanese National Health Insurance Research Database (NHIRD) to the question of whether yet more enhanced risk of adversity might be associated with a diagnosis of ADHD. Dementia by the way, reflects various symptoms/conditions pertinent to the decline of cognitive and other abilities.

Drawing on participant numbers in the hundreds, researchers determined that the risk of receipt of a dementia diagnosis in cases of adult ADHD was marginally higher compared with an asymptomatic (asymptomatic for ADHD) control group (5.4% vs. 4%). An association between ADHD diagnosis and risk of subsequent dementia remained after various, potentially interfering variables, were also taken into consideration ("age, gender, comorbidities, geographical area of residence, urbanization level of residence, and monthly income").

This is not the first time that enhanced risk of dementia in ADHD has been discussed in the peer-reviewed domain [2]. As per that previous report from Golimstok and colleagues - "there is no clear explanation for the association found" - science still does not have many clues as to why ADHD might preferentially predispose to certain types of dementia. I say this on the basis that we don't really know that much about the biology of either condition/diagnosis. That's not however to say that science is not getting closer to some important clues, as the report from Zhang and colleagues [3] talking about an animal model of Alzheimer's disease that also had "a high frequency of antecedent ADHD symptoms" is detailed. More studies are indicated.

To close, a link to an article marking the recent passing of the father of the ADHD diagnosis: Keith Conners together with a warning...

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[1] Tzeng NS. et al. Risk of Dementia in Adults With ADHD: A Nationwide, Population-Based Cohort Study in Taiwan. J Atten Disord. 2017 Jun 1:1087054717714057.

[2] Golimstok A. et al. Previous adult attention-deficit and hyperactivity disorder symptoms and risk of dementia with Lewy bodies: a case-control study. Eur J Neurol. 2011 Jan;18(1):78-84.

[3] Zhang Q. et al. Alzheimer's Model Develops Early ADHD Syndrome. J Neurol Neurophysiol. 2015;6(6):1-6.

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Wednesday, 22 February 2017

History of bipolar disorder = elevated risk of dementia: is vitamin D important?

"History of BD [bipolar disorder] is associated with significantly higher risk of dementia in older adults."

So said the systematic review and meta-analysis published by Breno Diniz and colleagues [1] taking in the accumulated peer-reviewed literature on this topic. Including data for some 3000 individuals diagnosed with bipolar disorder and nearly 200,000 controls (without bipolar disorder), authors calculated something of a significantly higher risk of dementia in those with a documented history of bipolar disorder. They note that there is more research to do in this area, specifically on mechanisms and "to evaluate interventions that may reduce the risk of dementia in this population."

Outside of the literature included in the Diniz study, similar findings have been reported in the science literature. The paper by Almeida and colleagues [2] noted that: "Bipolar disorder in later life is associated with increased risk of dementia" based on their analysis of ~38,000 older men (65-85 years old) and their "13-year risk of dementia." Perhaps more worryingly were their findings that: "Bipolar disorder was also associated with increased mortality" in relation to "death by suicide, accidents, pneumonia or influenza, and diseases of the liver and digestive system." Other data looking more generally at clinical depression paints a similar picture [3] suggesting something of a connection between various types of depression and risk of various types of dementia: "depressive symptomatology is associated with pathological mechanisms associated with neurodegeneration."

I've tackled the topic of dementia a couple of times on this blog; most recently in relation to how incidental vitamin D deficiency *could be* something important when it comes to at least some cases of dementia (see here). Minus any sweeping generalisations and accepting that there may be many different roads leading to dementia and/or bipolar disorder, I am intrigued at the possibility that the sunshine vitamin might be something to consider as a 'connector' between elements of the depression and dementia spectrums as per other findings (see here for example). At the very least, it invites lots more targeted investigation, including whether vitamin D might indeed be a nootropic of choice for some (see here)...

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[1] Diniz BS. et al. History of Bipolar Disorder and the Risk of Dementia: A Systematic Review and Meta-Analysis. The American Journal of Geriatric Psychiatry. 2017. Jan 4.

[2] Almeida OP. et al. Risk of dementia and death in community-dwelling older men with bipolar disorder. Br J Psychiatry. 2016 Aug;209(2):121-6.

[3] Cherbuin N. et al. Dementia risk estimates associated with measures of depression: a systematic review and meta-analysis. BMJ Open. 2015 Dec 21;5(12):e008853.

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ResearchBlogging.org Diniz BS, Teixeira AL, Cao F, Gildengers A, Soares JC, Butters MA, & Reynolds CF 3rd (2017). History of Bipolar Disorder and the Risk of Dementia: A Systematic Review and Meta-Analysis. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry PMID: 28161155

Friday, 27 January 2017

Vitamin D deficiency and risk of dementia

"The results of this systematic review show that low vitamin D levels might contribute to the development of dementia."

Whilst slightly off-topic when it comes to the core research material typically included on this blog, I did want to bring to your attention the systematic review and meta-analysis results published by Isolde Sommer and colleagues [1] (open-access) for your perusal. Although unable to "identify a single study investigating the association between sunlight exposure and dementia risk" authors did manage to find "indirect evidence from studies using vitamin D status as a surrogate parameter" where five out of six studies identified ("18,639 participants") suggested a possible correlation. Sunlight by the way, is the primary route of synthesising vitamin D.

The sort of 'risk' determined in the Sommer calculations when it comes to vitamin D levels and dementia is not to be sniffed at: "Translated into absolute numbers, 28 (at least 10 but up to 50 more) out of 1000 people with serious vitamin D deficiency would develop dementia compared with 1000 people with sufficient D levels over 18.03 years" despite some cautions around the quality of the studies reviewed.

Caveats? Well, examining just one variable (vitamin D status) when it comes to a nebulous condition like dementia has to be kept in mind when interpreting such data and another pet topic of mine - how one assays for vitamin D - is also mentioned: "There is still an ongoing debate regarding the method of choice but a recent comparison between liquid chromatography– tandem mass spectrometry (LC-MS/MS) methods and immunoassays showed variable performance of immunoassays apart from the radioimmunoassay that achieved a performance similar to LC-MS/MS." Discussions on this topic should also mention the epimers of vitamin D too [2]. Then there is the rather important issue of how the genetics of vitamin D formation/metabolism might also be something to look at [3] if one assumes some connection between small genetic 'blips' and possible risk, bearing in mind gene expression over just gene mutation might be important [4].

Minus any medical or clinical advice given or intended (something not given on this blog), I do however find data such as that from Sommer et al potentially important and something that can seemingly be acted upon quite easily (at least in terms of correcting any vitamin D deficiency/insufficiency). There is for example, a growing body of evidence potentially linking vitamin D and cognitive functions (see here) and alongside more population-wide advice being handed out by Government (see here), there seems to be some common sense in ensuring adequate sunlight exposure or vitamin intake.

Finally, minus any scaremongering or making connections where none might exist, specific groups of people where vitamin D deficiency seems to be 'over-represented' (see here and see here for example) might also be eligible for some enhanced screening for dementia in later life if one assumes a possible longitudinal link...

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[1] Sommer I. et al. Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis. BMC Geriatrics. 2017; 17: 16.

[2] Aghajafari F. et al. Plasma 3-Epi-25-Hydroxycholecalciferol Can Alter the Assessment of Vitamin D Status Using the Current Reference Ranges for Pregnant Women and Their Newborns. J Nutr. 2016 Jan;146(1):70-5.

[3] Lee YH. et al. Vitamin D receptor polymorphisms and susceptibility to Parkinson's disease and Alzheimer's disease: a meta-analysis. Neurol Sci. 2014 Dec;35(12):1947-53.

[4] Delgado-Morales R. & Esteller M. Opening up the DNA methylome of dementia. Mol Psychiatry. 2017 Jan 3.

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ResearchBlogging.org Sommer I, Griebler U, Kien C, Auer S, Klerings I, Hammer R, Holzer P, & Gartlehner G (2017). Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis. BMC geriatrics, 17 (1) PMID: 28086755

Friday, 10 July 2015

Vitamin D and cognitive function

'Correlation is not the same as causation' is an important theme in science, demonstrating how one always needs to be a little guarded about making too much of research linking one variable with another from a purely observational point of view.

I similarly apply such a principle to the findings reported by Rolf Jorde and colleagues [1] and the suggestion of "an association between serum 25(OH)D and cognition". Serum 25(OH)D levels by the way, refers to the measurement of calcifediol in serum, the biological precursor to the active form of vitamin D - the so-called sunshine vitamin/hormone.

Jorde et al report findings based on the the Tromsø Study [2], a population-wide initiative initiated in the early 1970s in Tromsø attempting to "help combat the high mortality of cardiovascular diseases in Norway." With a participant group in the thousands, the Tromsø Study has already provided a wealth of scientific information (see here) well beyond its original intentions (see here) and with vitamin D very much in mind (see here).

On this occasion, researchers looked at vitamin D levels and cognitive functions as measured by various psychometric schedules including the Mini–Mental State Examination (MMSE). Some 4500 participants were initially screened and tested for vitamin D levels and cognitive functions in a cross-sectional manner. Further: "in a prospective study serum 25(OH)D was measured in samples from 1994 and compared to cognitive function tested in 3436 subjects in 2001 and 2044 subjects in 2007." Just for good measure, researchers also looked for the presence of genetic polymorphisms in the vitamin D receptor (VDR) gene.

The results pointed towards to some rather interesting trends perhaps requiring greater scientific scrutiny. "In the cross-sectional study all tests were positively associated with serum 25(OH)D levels with ~5% better performance in subjects in the highest versus lowest serum 25(OH)D quartile." In other words bearing in mind that correlation ≠ causation, vitamin D levels 'might' play some role in cognitive ability specifically "in subjects older than 65 years." In the prospective portion of the study: "serum 25(OH)D from 1994 similarly predicted cognitive function 7-13 years later." Such observations have led to calls for "randomized controlled trials... to establish causality."

Once again reiterating that two correlating values do not a causative relationship make, this is not the first time that vitamin D and cognition have shown up on the peer-reviewed research radar. The literature on vitamin D and cognition with ageing [3] and dementia in mind [4] is testament to the interest in a possible link. That being said, I wouldn't want anyone to believe that such a relationship between vitamin D and cognition is straight-forward given that ageing for example, includes an array of biological processes that might link into both vitamin D levels and cognitive ability [5]. That also such a relationship does not appear to be present in children and young adults [6] provides a word of caution for those who might see vitamin D as the new nootropic of choice.

Still, these results are interesting and alongside other research from Jorde et al [7] suggest that the extra-skeletal input/effects of vitamin D are deserving of quite a bit more study and appreciation...

Music: R.E.M. - Everybody Hurts

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[1] Jorde R. et al. Vitamin D and cognitive function: The Tromsø Study. J Neurol Sci. 2015 Jun 7. pii: S0022-510X(15)00350-0.

[2] Jacobsen BK. et al. Cohort profile: the Tromso Study. Int J Epidemiol. 2012 Aug;41(4):961-7.

[3] Toffanello ED. et al. Vitamin D deficiency predicts cognitive decline in older men and women: The Pro.V.A. Study. Neurology. 2014 Dec 9;83(24):2292-8.

[4] Nagel G. et al. Serum Vitamin D Concentrations and Cognitive Function in a Population-Based Study among Older Adults in South Germany. J Alzheimers Dis. 2015 Feb 3.

[5] Visser M. et al. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003 Dec;88(12):5766-72.

[6] Tolppanen AM. et al. The association of circulating 25-hydroxyvitamin D and calcium with cognitive performance in adolescents: cross-sectional study using data from the third National Health and Nutrition Examination Survey. Paediatr Perinat Epidemiol. 2011 Jan;25(1):67-74.

[7] Jorde R. et al. Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels. The Tromsø study. J Neurol. 2006 Apr;253(4):464-70.

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ResearchBlogging.org Jorde R, Mathiesen EB, Rogne S, Wilsgaard T, Kjærgaard M, Grimnes G, & Schirmer H (2015). Vitamin D and cognitive function: The Tromsø Study. Journal of the neurological sciences PMID: 26092373

Sunday, 10 August 2014

Vitamin D deficiency and dementia risk: a micropost

I'm a little late in getting to the paper by Thomas Littlejohns and colleagues [1] (open-access) reporting that: "vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease". The media have been all over this study as per the BBC commentary (see here) and some rather more critical discussion by the NHS Choices website (see here).

I don't need to add anything further to discussions aside from saying that correlation might not necessarily be the same as causation and any mechanism linking vitamin D status and cognitive abilities is still something to be determined. But that's not to say that there aren't interesting things afoot for vitamin D outside of it's more traditional skeletal effects...

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[1] Littlejohns TJ. et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014. August 6.

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Monday, 18 July 2011

Painkillers vs antipsychotics in dementia care

A very, very short post this one (I promise). The news here in the UK has been abuzz with lots of things today (that newspaper, that media baron, etc) but in amongst the talk of resignations, and Parliamentary hearings, a piece appeared on the BBC website about a new study published in the British Medical Journal (BMJ).

The study is here (full-text) and suggests that using various analgesics, including paracetamol (acetaminophen), with patients with dementia might decrease levels of 'agitation' over and above that which might be expected from the use of various antipsychotics, traditionally the first line of treatment for such issues. People with dementia can suffer pain (believe it or not!) and antipsychotics are not necessarily the best analgesic.

I am still digesting the study, its very comprehensive methodology and its findings, but already a few parallels are emerging with autism spectrum conditions. Principal among them is the notion that not every 'ill' that a person with autism might present with is necessarily due to their autism. I have hinted about this in a previous post on self-injurious behaviour (SIB) and the so-called challenging behaviours in autism. One could also conceivably see some relationship to the various bowel problems associated with some cases of autism and particularly Buie and colleagues' assertion about gastrointestinal problems, pain and 'aberrant behaviours' related to autism.  

Worth a look.