Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Anti-psychotics--a fundamental mismatch for dementia
- ZEKRIA IBRAHIMI (17 February 2009)
-
Mild Cognitive Impairment (MCI) is not a clinical entity
- Orazio Zanetti, Cristina Geroldi, Giovanni B. Frisoni (18 February 2009)
-
Vitamin B12 assessment in dementia
- Sunku H Guptha, Rukayat Lawal (20 February 2009)
-
Normal pressure hydrocephalus: a reversible cause of dementia
- Laurence D Watkins, Andrew Tarnaris and Ahmed Toma (3 March 2009)
|
|
|||
|
ZEKRIA IBRAHIMI, psychiatric patient Coombs Library UB1 3EU
Send response to journal:
|
It would be wrong- and absurd- to treat a broken leg by putting the arm in a sling. Yet, by analogy, we still give up to half of the patients with dementia in institutions anti- psychotic drugs (1), against the FDA warning. Anti- psychotic drugs were never devised for Alzheimer's or Lewy bodies dementia, but were intended for schizophrenia. The anti- psychotics block dopamine pathways. The general pathology of dementia is a decay in acetycholine muscarinic receptors, which mediate memory. 'Dysfunction of M1 receptors, which are always inhibitory, has been implicated in dementia ...' (2) Anti- psychotics put up additional neurochemical hurdles in a brain that is already slowing down because of dementia. This broad brush article by Burns and Iliffe in the BMJ refers to five anti- psychotics: quetiapine: risperidone; olanzapine; aripiprazole; and (for extreme cases) haloperidol. From the difficult details of the psychopharmacology, we would expect olanzapine to be potentially dangerous in Alzheimer's, because it inhibits the muscarinic receptors that are already being attacked by dementia. And, indeed, Eli Lilley, which produces olanzapine, has suffered a fine of over a billion dollars for off - label marketing of olanzpine in dementia and other ailments(3). One study in Finland found that all psychotropic drugs- antipsychotics, antidepressants and anxiolytics- were associated with more mortality in the elderly with dementia (4). The study implied that prescribing practices were inconsistent, and that there was insufficient use of cholinesterase inhibitors for dementia. Another Scandinavian study, from Norway, declared: 'most patients showed stable, or improved, symptom scores after antipsychotic cessation'(5). Dementia with Lewy's body is linked to Parkinson's and involves the degeneration of both the dopamine and acteylcholine muscarinic systems. With this sort of dementia, it is accepted that anti- psychotics are not appropriate(6). So why are they still so common with Alzheimer's? Perhaps there is pressure by the drug companies to make anti- psychotics spill over from the field of schizophrenia into dementia and also learning disabilities(7). We are not considering the receptor profiles and the side effects enough of psychotropic drugs being misapplied to the elderly under the deadly shadow of Alzheimer's. Pensioners do not always survive the treatment, let alone the disease. Anti- psychotics are not a universal miracle and they will not cure everything. REFERENCES: (1) Dementia. Alistair Burns, Steve Iliffe, BMJ 2009;338:b75 (2) Core Psychopharmacology. Padraig Wright. Saunders Elsevier. (Pg. 36) (3) Eli Lilley pays record fines of $1.4 bn for promoting off- label use of olanzapine for common disorders. Zosia Kmietowicz. BMJ 2009;338:b217 (4) The use of psychotropics and survival in demented elderly individuals. International Clinical Psychopharmacology. Sirpa Hartikainen et al. 2005, 20:227-231 (5) Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo- controlled study- The Bergen District Nursing Home Study (BEDNURS). Sabine Ruths et al. International Journal of Geriatric Psychiatry 2008: 23: 889-895. (6) Oxford Textbook of Old Age Psychiatry. Ed. by R. Jacoby et al. Chapter 27v. Clinical aspects of dementia: dementia in Parkinson's disease and dementia with Lewy bodies. R. McShane. Pgs. 455-56. (7) Mad In America. Bad Science, Bad medicine, and the Enduring Mistreatment of the Mentally ill. Robert Whitaker. Perseus. 2002. Pg. 205 Competing interests: None declared |
|||
|
|
|||
|
Orazio Zanetti, Head Geriatrician IRCCS Centro S.Giovanni di Dio-Fatebenefratelli, Via Pilastroni 4, 25100 Brescia, Italy, Cristina Geroldi, Giovanni B. Frisoni
Send response to journal:
|
We read with interest the excellent Clinical Reviews by Professors Burns and Iliffe on dementia (BMJ 2009; 338:b75) and Alzheimer’s disease (BMJ 2009; 338:b158). We agree completely with the first claiming that dementia care needs a multidisciplinal and diachronic approach. As to the second article addressing “the benefit of identifying mild cognitive impairment”, the authors acknowledge that “the usefulness of such early “preclinical” diagnosis (MCI) remains uncertain”, but give wide space to the “criteria” for diagnosing MCI and emphasizing that “it may be a precursor to Alzheimer’s disease”. After eighteen years of debate, the first operational definition of mild cognitive impairment having been suggested in 1991 by Flicker and colleagues (1), we believe that the ambiguous term MCI should no longer be used in clinical practice because it is not useful from a prognostic (2) and therapeutical (3) perspective. Moreover, it promotes medicalization of normal ageing and brings huge problems on diagnostic disclosure (4). Data from a study carried out in our memory clinic from November 2002 to March 2005 indicate that after a mean time to follow-up of 41 months 73/164 (13.5% per year) MCI patients had converted to dementia, 63% of whom to Alzheimer’s disease (AD). It should be underlined that the majority of conversions (n=52, 71%) occurred during the first 2 years of observation and that 49% (n=43) of the stable subjects have been followed for as long as 4 years, consistently with the notion that only a proportion of MCI patients have AD. New diagnostic tools are now available that might help recognizing patients with incipient AD (hippocampal volumetry, CSF Tau and Abeta, and FDG-PET) (5), and dementia with Lewy Bodies (SPET with DaTSCAN, also cited in the Burns and Iliffe’s review). Other biological markers are emerging as useful in the differential diagnosis between "normal ageing" and neurodegenerative diseases (6). We believe that the use of these biological and neuroimaging markers should be reserved to selected patients. About 9% of first referrals to our outpatient memory clinic (200 out of the 2,300 of the year 2008) required such advanced diagnostic workup (high resolution MRI with hippocampal volumetry, FDG-PET, and lumbar tap for CSF tau and abeta42 assaying). It is high time to leave the term “MCI” in the everyday clinical practice and explore the diagnostic accuracy of the modern diagnostic tools that may allow to recognize AD at the MCI stage and plan the appropriate care interventions for patients and their family. Yours sincerely Orazio Zanetti, MD, Head geriatrician
Cristina Geroldi, MD, PhD, Senior Geriatrician
Giovanni B Frisoni, MD, Deputy Scientific Director
REFERENCES 1) Flicker C., Ferris SH, Reisberg B. Mild cognitive impairment in the elderly: predicotors of dementia. Neurology 1991;41:1006-9 2) Visser PJ, Kester A, Jolles J, Verhey F. Ten-year risk of dementia in subjects with mild cognitive impairment. Neurology. 2006 Oct 10;67(7):1201 -7) 3) Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al.: Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379-88. 4) Whitehouse PJ, Juengst ET. Antiaging medicine and mild cognitive impairment: practice and policy issues for geriatrics. Am J Geriatr Soc. 2005;53:1417-22. 5) Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al.: Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6:734-46. 6) Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, et al.: Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med. 2007;13:1359-62. Competing interests: None declared |
|||
|
|
|||
|
Sunku H Guptha, Consultant Physician Medicine for Older People, Edith Cavell Hospital, Peterborough PE3 9GZ, Rukayat Lawal
Send response to journal:
|
The role of vitamin B12 in evaluation of progressive cognitive decline is not established.[1] A prospective trial over 3.9 years did not find any association with risk of Alzheimer’s dementia and dietary B12 intake[2] and a randomized controlled trial supplementing oral B12 did not find any effect on cognitive decline in Alzheimer’s disease.[3] Guidelines from National Institute of Clinical Excellence however recommend testing vitamin B12 levels as part of assessment of cognitive impairment preferably in primary care setting.[4] It is however common practice to test B12 levels as part of so called “dementia screen” in secondary care. We audited the use of B12 amongst other investigations for inpatients admitted with acute medical illness and cognitive impairment. Of the 50 patients selected randomly over 6 months, all of them had either normal or high values but crucially in none of the patients, the vitamin B12 level did not have any bearing on the final diagnosis. Even if the vitamin B12 levels had returned low the responsible physician felt that it would not have accounted for the symptoms in any of the patients. Of the 50 patients, 16 had coexisting anaemia where B12 levels would have been helpful in diagnosis. We agree with Burns and Iliffe’s recommendations that vitamin B12 should be included as part of assessment of cognitive impairment in patients with coexisting anaemia.[5] References: 1. Crystal HA, Ortof E, Frishman WH, Gruber A, Hershman D, Aronson M. Serum vitamin B12 levels and incidence of dementia in a healthy elderly population: a report from Bronx Longitudinal Ageing study. J Am Geriatr Soc 1994;42(9): 933-36. 2. Morris MC, Evans DA, Schneider JA, Tangney CC, Bienias JL, Aggarwal NT. Dietary folate and vitamins B12 and B6 not associated with incidence of Alzheimer’s disease. Journal of Alzheimer’s disease 2006; 9(4): 435-443. 3. Aisen PS, Schneider LS, Sano M et al. High dose vitamin B12 supplementation and cognitive decline in Alzheimer’s disease. JAMA 2008; 306(15): 1774-1783. 4. National Institute for Health and Clinical Excellence, Social Care Institute for Excellence. Dementia: supporting people with dementia and their carers in health and social care. 2006. www.nice.org.uk/Guidance/CG42 5. Burns A, Iliffe S. Dementia. BMJ 2009; 338: 405-409. Competing interests: None declared |
|||
|
|
|||
|
Laurence D Watkins, Consultant Neurosurgeon Victor Horsley Department of Neurosurgery, Andrew Tarnaris and Ahmed Toma
Send response to journal:
|
We read with interest the review by Burns and Iliffe (BMJ 2009; 338:b75) with its very timely focus on dementia and its various causes. However, we were concerned that Normal Pressure Hydrocephalus (NPH) was mentioned only briefly. This condition perhaps deserves much greater emphasis, since it is a potentially reversible condition and may be a contributory factor in up to 5% of the dementia population.1
Normal pressure (or chronic adult) hydrocephalus affects the ageing population (usually over 60 years old) and typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. CSF pressure appears “normal” and brain imaging shows ventriculomegaly. Symptoms may be improved by surgical CSF diversion, especially if picked up early.2
Recent population-based studies have estimated the prevalence of NPH to be about 0.5% in those over 65 years old, with an incidence of about 5.5/100,000/year.3,4 Quality of life of patients treated by shunt insertion can improve substantially and the improvement can be long-lasting.5,6 Yet, less than 350 shunt insertion surgeries operations are performed in the UK for normal pressure hydrocephalus each year, representing a fraction of about 10% of the expected incidence (UK shunt registry, personal communication). The authors mentioned that NPH should be excluded via neurocognitive assessment and (if available) computed tomogragraphy. Although CT scan of the brain is essential to establish ventriculomegaly as a prerequisite for the diagnosis of NPH,7 the sensitivity of neuropsychological assessment and brain imaging are low in diagnosing this condition and referral to specialized neurosurgical centre to conduct further testing by either lumbar drainage or assessment of CSF dynamics is essential.8 We certainly welcome the current expansion of services aimed at improving provision for dementia patients and would encourage inclusion of NPH in all diagnostic algorithms. It is important to consider the possible diagnosis if there is ventriculomegaly and the patient is fit enough to be a surgical candidate. If the diagnosis is being considered, then it should not be excluded except by invasive testing (such as extended lumbar drainage), which generally will mean referral to a specialist unit.9 References: 1. Silverberg G, Mayo M, Saul T, Fellmann J, McGuire D. Elevated cerebrospinal fluid pressure in patients with Alzheimer’s disease. Cerebrospinal Fluid Research 2006;3:7. 2. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S4-16 3. Tanaka N, Yamaguchi S, Ishikawa H, Ishii H, Meguro K. Prevalence of Possible Idiopathic Normal-Pressure Hydrocephalus in Japan: The Osaki-Tajiri Project. Neuroepidemiology 2008;32(3):171-5. 4. Brean A, Eide PK. Prevalence of probable idiopathic normal pressure hydrocephalus in a Norwegian population. Acta Neurologica Scandinavica 2008;118(1):48-53. 5. Stein SC, Burnett MG, Sonnad SS. Shunts in normal-pressure hydrocephalus: do we place too many or too few? J Neurosurg 2006;105(6):815-22. 6. Pujari S, Kharkar S, Metellus P, Shuck J, Williams MA, Rigamonti D. Normal Pressure Hydrocephalus: Very long term outcome after shunt surgery. J Neurol Neurosurg Psychiatry 2008;79(11):1282-6 7. Tarnaris A, Kitchen ND, Watkins LD. Noninvasive biomarkers in normal pressure hydrocephalus: evidence for the role of neuroimaging. J Neurosurg. [Epub ahead of print] JNS, November 7, 2008; http://thejns.org/doi/abs/10.3171/2007.9.17572. 8. Marmarou A, Bergsneider M, Klinge P, Relkin N, Black PM. The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S17-28. 9. Batra S, Rigamonti D. Idiopathic normal pressure hydrocephalus: the benefits and problems of shunting. Nat Clin Pract Neurol. 2009; 5(2):80-1. Competing interests: The Clinical Research Fellow at Victor Horsley department of Neurosurgery at the National Hospital for Neurology and Neurosurgery salary is supported by a grant from B. Braun Medical Ltd |
|||