Cobalamin Deficiency in Older Adults

Emmanuel Andrès, MD, Professor of Internal Medicine, Strasbourg University; Head of the Department of Internal Medicine, Diabetes and Metabolic Diseases, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Mustapha Mecili, MD, Clinical Specialist, Department of Internal Medicine, Diabetes and Metabolic Diseases, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Helen Fothergill, MD, Clinical Specialist, Department of Internal Medicine, Diabetes and Metabolic Diseases, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Thomas Vogel, MD, Clinical Specialist, Department of Internal Medicine and Geriatrics, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Laure Federici, MD,Clinical Specialist, Department of Medicine, Hôpitaux de Colmar, Colmar, France.
Jacques Zimmer, MD PhD, Clinical Researcher, Laboratoire d’Immunogénétique-Allergologie, Centre de Recherche Public de la Santé (CRP-Santé) de Luxembourg, Luxembourg.

Cobalamin (vitamin B12) deficiency is particularly common in among older adults, although it is frequently undiagnosed as the clinical presentations may be subtle. However, serious complications do occur, in particular neuropsychiatric and hematological disorders. In older adults, the main causes of cobalamin deficiency are food-cobalamin malabsorption (50–60%) and pernicious anemia (30–40%). Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is frequently associated with atrophic gastritis, which may be a result of Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. The management of cobalamin deficiency with cobalamin injections is currently well documented, however new routes of cobalamin administration (including via oral and nasal passages) are being studied. Oral cobalamin therapy is of particular interest in the management of food-cobalamin malabsorption syndrome.
Key words: cobalamin, vitamin B12, cobalamin deficiency, food-cobalamin malabsorption, oral cobalamin therapy.

Myelodysplastic Syndromes in Older Adults

Lisa Chodirker, MD, FRCPC, Clinical Fellow, Division of Hematology/Oncology, Odette Cancer Centre*, Sunnybrook Health Sciences Centre, Toronto, ON.
Rena Buckstein, MD, FRCPC, Co-director of MDS research programs, Division of Hematology/Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON.

Myelodysplastic syndromes (MDS) are among the most common hematological malignancies in Western countries, with a median age at diagnosis of 74. They are a stem cell disorder characterized by cellular dysplasia, cytopenias, and an increased risk of transformation to acute myeloid leukemia. Disease trajectory is commonly determined by the international and world prognostic scoring systems (International Prognostic Scoring System and the World Health Organization [WHO] classification–based prognostic scoring system) and the WHO classification. Some patients have an indolent disease course, while others experience a rapid deterioration and short overall survival. For many years, the mainstay of therapy was supportive care with blood transfusions and hematopoietic growth factors. Fortunately, novel effective agents including lenalidomide, hypomethylating agents, and oral iron chelators have emerged over the past 5–10 years that improve transfusion dependence and may alter the natural history of the disease. These new therapeutic options offer new hope for individuals with MDS and bolster the role for the investigation of unexplained cytopenias in the older patient.
Key words: myelodysplastic syndrome, erythropoietin, anemia, red blood cell transfusions, stem cell disorder.

Approach to Thrombocytopenia in Older Adults

Mohammed E. Hussain, Department of Medicine, Mount Sinai Hospital, Toronto, ON.
Dominick Amato, Department of Medicine, Mount Sinai Hospital; Department of Medicine, University of Toronto, Toronto, ON.

Thrombocytopenia, whether symptomatic or not, is a relatively common finding in clinical medicine. The causes of thrombocytopenia are many, and all of these may be found at all ages. However, just as the frequencies of these causes vary between pediatric and adult age-groups, so too is there variation between younger adults and older individuals. Also, the pathophysiological approach to thrombocytopenia (decreased production, increased destruction, sequestration, dilution) remains just as valid to the seasoned hematologist as to the neophyte. In this article, we provide a suggested approach to the patient with thrombocytopenia, with emphasis on the more common causes in older adults.
Key words: thrombocytopenia, platelets, bleeding disorders, primary hemostasis, older adults.

No Simple Algorithm

It seems that regardless of the focus of our issue, I have just had a patient or occurrence that makes the theme resonate even more. This issue’s focus is on hematology in older adults, and just yesterday I had the honour of examining a colleague’s 92-year-old mother regarding her hematological disorder. Her major complaint was weakness and fatigue (she lives in her own apartment with little professional help), and she had been diagnosed years ago as having chronic lymphocytic leukemia. Her current problems are likely related to the tremendous increase in her white cells over the last two months. Diagnosis is easy in this case, but the judgment issue of if and how treatment will progress is very difficult. This is one of the challenges of geriatric practice: no simple algorithm is available for making these difficult decisions. That is also one of the great joys as well, in that individual assessment and planning make a huge difference.

I have always enjoyed hematology, perhaps because of the opportunity to see the beautiful slides that the hematologists review on a regular basis. Our CME article is on a topic that is quite important and common in geriatric practice, namely the “Approach to Thrombocytopenia in Older Adults” by Dr. Mohammed E. Hussain and Dr. Dominic Amato. We often order vitamin B12 levels in clinical practice, and the article “Cobalamin Deficiency in Older Adults” by Dr. Emmanuel Andrès, Dr. Mustapha Mecili, Dr. Helen Fothergill, Dr. Thomas Vogel, Dr. Laure Federici, and Dr. Jacques Zimmer will aid us in using the information we obtain in a rational manner. One of the common, and often poorly understood, causes of anemia in older people is addressed in the article “Myelodysplastic Syndromes in Older Adults” by Dr. Lisa Chodirker and Dr. Rena Buckstein.

Of course, we have our usual collection of useful articles on various geriatric topics. “Management of Hypercholesterolemia” is addressed by our frequent and brilliant contributor Dr. Wilbert S. Aronow. We often are concerned about the choices our patients make and wonder if they are capable in making those decisions. These issues are addressed in the article “Overview of Mental Capacity Assessments” by Dr. Michel Silberfeld. For caregivers of patients with dementia, the common day-to-day tasks are often what give the most problems. One of these tasks is addressed in the article “How to Bathe A Person with Dementia: An Evidence-Based Guide” by Dr. Ellen Costello and Dr. Mary Corcoran. Finally, in our geriatrician column we profile Dr. Ken Madden, the co-editor of the Canadian Journal of Geriatrics.

Enjoy this issue,
Barry Goldlist

Le vieillissement normal : immunologie et hématologie

Le vieillissement normal : immunologie et hématologie

Conférencier : Shabbir M.H. Alibhai, M.D., M.Sc., FRCP(C), Division de la médecine gériatrique, Université de Toronto; Chercheur scientifique, Société canadienne du cancer, Toronto, ON

Le D^r Shabbir Alibhai a adressé les changements des systèmes immunologique et hématologique qui se produisent avec le vieillissement et leurs implications cliniques.

Il a souligné la pertinence de l’homéosténose, défini par GE Taffett comme une constriction progressive des réserves homéostatiques qui se produit avec le vieillissement (c. à d., une habilité réduite, dans le temps, de faire face aux perturbations et stress externes). Tous les systèmes vieillissent et subissent un dérèglement avec une amplification des processus indésirables. Il a précisé que les effets de l’âge sur les paramètres de la santé varient significativement et augmentent avec le vieillissement. De plus, le rôle des facteurs comportementaux et environnementaux sur la santé n’est pas bien compris. Il a de même averti que le défi d’identifier le meilleur modèle du vieillissement normal chez les humains ne devrait pas être sous-estimé, et non plus le rôle que joue le biais de sélection dans les publications d’études du vieillissement.

Le D^r Alibhai a noté que son intérêt porte surtout sur les lignées cellulaires de lymphocytes B et lymphocytes T qui interagissent significativement dans le système immunologique. Le D^r Alibhai a affirmé que beaucoup de ce qui est connu dans ce domaine provient de recherches in vitro approfondies. Il est nettement plus difficile en immunologie d’obtenir des recherches in vivo; la manutention in vitro est problématique du fait que les manipulations peuvent causer une altération et une perturbation des fonctions cellulaires. Certains résultats in vitro ont une pertinence clinique limitée ou des implications non vérifiées. Finalement, les résultats provenant du modèle animal sont variablement dupliqués dans les études chez les humains.

Le système immunitaire est composé de l’immunité innée et de l’immunité adaptative ou acquise (divisées en composantes cellulaires et humorales). Le D^r Alibhai a noté l’artificialité de la distinction étant donné la complexité de la relation entre les lymphocytes B et lymphocytes T en présence d’infection et d’autres syndromes du dérèglement immunitaire.

L’immunité innée est la première ligne de défense. L’immunité innée fournit une défense rapide, mais incomplète contre les attaques étrangères jusqu’à ce que la réponse immunitaire acquise qui est plus lente, mais plus définitive se développe.

Les cellules dendritiques sont d’une grande importance dans le déclenchement de la réponse immunitaire et comme cellules présentant l’antigène; elles font parvenir des signaux d’activation aux lymphocytes T. Des études chez des sujets humains ont généralement démontré une aptitude de présentation de l’antigène équivalente chez les plus vieux et les plus jeunes, aussi bien qu’une aptitude équivalente à induire la prolifération des lymphocytes T.

Il a ensuite parlé du rôle des macrophages, cellules qui sont activées tôt dans la défense immunitaire. Certaines preuves démontrent une fonction détériorée avec l’âge, ce qui porte à conséquence étant donné leur rôle dans la phagocytose et la destruction intracellulaire, et comme cellules présentant l’antigène pour le reste du corps. Avec l’âge, l’activation non spécifique est plus commune, cependant il y a une capacité réduite de la production du facteur de nécrose tumorale (TNF), l’interleukine (IL)-1, et l’oxyde nitrique (essentiel à l’inhibition de la croissance de tumeurs et à la stimulation des défenses immunitaires). Le D^r Alibhai a décrit leur fonctionnement comme « hyperactif »; leur dysfonctionnement peut contribuer à un ralentissement de la cicatrisation des plaies.

Le D^r Alibhai a ensuite détaillé le rôle des cellules tueuses naturelles (NK) qui détruisent spontanément les cellules ciblées sans activation. Il est incertain si le nombre de cellules NK ou leur activité changent avec l’âge. Afin d’activer les cellules NK au maximum, un taux plus élevé d’interféron a serait peut-être re-quis.

Finalement, le système complémentaire est important pour le fonctionnement du système immunitaire inné. Le D^r Alibhai l’a décrit comme un système enzymatique qui catalyse d’autres réactions par la cytolyse, activant ainsi la cascade inflammatoire. Le système complémentaire exemplifie l’homéosténose, puisque lorsqu’un animal plus vieux est inoculé, la voie complémentaire ne se déclenche pas d’une efficacité maximale.

Le système complémentaire se compose de 20 protéines plasmatiques qui interagissent entre elles et qui constituent un système enzymatique qui défend contre les microorganismes par cytolyse, opsonisation et par activation de l’inflammation. Certaines composantes du complément sont légèrement plus élevées avec le vieillissement, mais les taux de complément n’augmentent pas avec les infections bactériennes chez les aînés et par conséquent la réponse immunitaire à l’infection est atténuée.

Portant son attention à l’immunité adaptative, le D^r Alibhai a décrit les composantes principales : les lymphocytes B (provenant de la moelle osseuse) et les lymphocytes T (provenant du thymus). Ils reconnaissent les corps étrangers par reconnaissance peptidique. Le thymus est l’endroit principal pour le développement des lymphocytes T; 95 % des thymocytes sont éliminés in situ ou par apoptose. Le dérèglement augmente avec le vieillissement : l’involution thymique commence à la naissance et subit une involution importante de 90 % par l’âge de 60, au-delà duquel les hormones thymiques ne sont plus détectables dans le sérum.

La défectuosité de la plus haute importance avec le vieillissement est la perte de la fonction des lymphocytes T auxiliaires (causé par une baisse de la production d’anticorps, une capacité réduite d’expansion sous attaque et une différentiation incomplète). La réponse proliférative des lymphocytes T aux lectines mitogéniques est atténuée; d’autres exemples de sa dérégulation comprennent une manifestation de ca-ractéristiques aberrantes avec le vieillissement. Chez les aînés, les lymphocytes T, une fois activés, sont plus aptes à initier l’apoptose et sont plus lentement remplacés.

Portant son attention aux lymphocytes B, le D^r Alibhai a déclaré que leur plus important rôle est de produire des anticorps comme partie de la réponse humorale. Avec le vieillissement, cette réponse est affaiblie de façon qualitative et quantitative. Les aînés ont une réponse atténuée à l’immunisation avec une plus faible production d’anticorps. Les anticorps naturels déclinent avec l’âge dû à la perte de lymphocytes B et la fréquence de la réponse antigénique des lymphocytes B diminue — le nombre de cellules est non seulement moindre, mais dans le temps jusqu’à 30 % deviennent non fonctionnelles. D’autres importants changements comprennent une augmentation de la production d’IgG non spécifique; de plus, les lymphocytes B peuvent être chroniquement activés et présenter d’autres formes de dérèglements. Il semble y avoir une augmentation de l’activité auto-immune avec le vieillissement, avec une fréquence plus élevée d’auto-anticorps contre des antigènes spécifiques et non spécifiques aux organes. La signification clinique de ces auto-anticorps demeure contestée.

De plus, le D^r Alibhai a parlé des changements immunologiques du système de la muqueuse. Soulignant la lacune de bonnes données, il a mentionné que l’intégrité de la muqueuse semble se dégrader avec l’âge et il y a possibilité de défectuosités de la production locale d’anticorps.

Par rapport à une allergénicité modifiée, il semblerait que les réactions d’hypersensibilité causées par l’IgE sont moins fréquentes avec le vieillissement, mais ceci demeure hypothétique. La production sérique de l’IgE décline avec l’âge et entre autres formes de dérèglements on retrouve une déficience de la production d’IL-4.

L’âge apporte des dérèglements plus fréquents du système de cytokine — une série complexe de protéines pro-inflammatoires et anti-inflammatoires qui interagissent entre elles et aident à régulariser le système immunitaire — avec des changements importants mettant en jeu l’IL-6 (Figure 1). L’augmentation de l’IL-6 associée à l’âge est une importante perturbation des cytokines, a affirmé le D^r Alibhai, et peut accompagner une inflammation chronique; ceci mène à une résorption de l’os, peut jouer un rôle dans la maladie d’Alzheimer et peut causer une morta-lité excessive à moyen terme. La production d’IL-1 diminue avec l’âge et la production et la faculté de réponse de l’IL-2 sont atténuées. Puisque les cytokines n’agissent pas indépendamment, il a noté qu’il est difficile de déterminer quelles modifications des cytokines sont importantes. Au fil du temps, la réponse des lymphocytes T à l’infection est plus élevée que celle des lymphocytes B. On ne peut attribuer tous les changements au vieillissement en soi; la maladie subclinique et les facteurs environnementaux y jouent sans doute un rôle.

 

La conséquence clinique chez les aînés est la prédisposition à l’infection, mais pas à une déficience immunitaire manifeste. Il y a un risque croissant de réactivation d’infections latentes tels que le zona et les infections mycobactériennes. Ces risques s’aggravent avec la maladie et la malnutrition. De plus, les vaccinations sont moins efficaces et il y a un risque croissant d’infection parasitaire.

Les options de traitement pour inverser les changements du vieillissement sont limitées en raison d’un manque d’études de haute qualité, à long terme, et puisque l’innocuité et l’effica-cité des agents thérapeutiques prometteurs ne sont pas clairement établies. De nouvelles preuves suggèrent que la mélatonine serait potentiellement de valeur pour augmenter la production d’anticorps et l’activité des lymphocytes T, et pourrait peut-être stimuler la production de l’IL-2. D’autres données suggèrent qu’une alimentation nutritionnelle mo-difiée a des effets positifs sur la santé (p. ex., une amélioration de l’immunité par une plus grande consommation d’acides gras polyinsaturés et de vitamine E); de plus, une modification au calendrier d’immunisation (p. ex. de plus nombreuses doses du vaccin d’hépatite B chez les aînés) démontre des bénéfices, mais de plus grandes études sont requises.

La prochaine section de la présentation a porté sur les changements du système hématologique avec l’âge. Habituellement, la concentration de la majorité des éléments du sang ne changent pas avec l’âge. L’anémie devient cependant beaucoup plus commune avec l’âge, mais n’est pas fondamentalement liée à l’âge (les réserves de fer du corps augmentent avec l’âge); elle serait plutôt attribuable à la maladie ou à d’autres facteurs (p. ex., légères carences alimentaires). Il est possible que le taux d’hémoglobine baisse légèrement avec l’âge quoique ceci demeure controversé. Plus important encore, la moelle osseuse âgée ne peut répondre rapidement à une grave perte de sang. Il faut donc plus de temps pour corriger une anémie aigüe en fabriquant de nouveaux érythrocytes. Le D^r Alibhai a rappelé à l’auditoire que le nombre du total des leucocytes ne change pas avec l’âge, mais la réponse aux stress est atténuée. Le nombre de neutrophiles et de monocytes ne change pas avec l’âge, cependant le nombre de lymphocytes baisse légèrement. Paradoxalement, en présence d’une infection bactérienne, il y a des baisses du nombre et du taux de prolifération des neutrophiles précurseurs, partiellement à cause du dérèglement des cytokines. Les neutrophiles vieillissants ont une capacité réduite de migration au site de blessure et de génération d’oxydants antimicrobiens en réponse à une attaque. Les lymphocytes vieillissants sont plus vulnérables aux effets néfastes de la radiation.

Avec l’âge, l’hypercoagulabilité et une augmentation de la viscosité des érythrocytes sont possibles, mais les données sont incertaines.
Les implications cliniques de ces changements hématologiques comprennent une prédisposition plus élevée chez les aînés de développer et maintenir une anémie en réponse à un saignement. Il a réitéré que l’anémie n’est pas occasionnée par le vieillissement et requiert des investigations. Quant aux dangers de l’anémie, il a préconisé que les physiciens surveillent son association avec la fatigue, une guérison plus lente d’une incapacité AQV, des fonctions exécutives détériorées, des symptômes de dépression, un taux d’hospitalisation croissant et un taux de mortalité croissant. Que ce soit en partie cause ou corrélation est toujours sous investigation.
Une autre implication clinique veut que les individus qui subissent une suppression de la moelle osseuse (p. ex. avec la chimiothérapie), soient habituellement recommandés un facteur de croissance hématopoïétique (p. ex., facteur de croissance des granulocytes) comme prophylaxie de neutropénie dans un milieu oncologique.

En conclusion, il a souligné que les indices hématologiques ne changent pas avec l’âge et que les tests non effractifs pour l’anémie (ferritine, B12, acide folique des GR, etc.) sont aussi sensibles et spécifiques que chez les individus plus jeunes. Le D^r Alibhai a attiré l’attention sur les preuves que l’hyperréticulocytose se détériore avec le vieillissement, que la réponse réticulocyte à une administration d’érythropoïétine est atténuée et que d’autres réserves de la moelle osseuse baissent en réponse à une demande croissante.

Normal Aging: Immunology & Haematology

Normal Aging: Immunology & Haematology

Speaker: Shabbir M.H. Alibhai, MD, MSc, FRCP(C), Division of Geriatric Medicine, University of Toronto; Research Scientist, Canadian Cancer Society, Toronto, ON.

Dr. Shabbir Alibhai addressed changes in the immunological and haematological systems with aging, and their clinical implications.
He emphasized the relevance of homeostenosis, defined by GE Taffett as a hallmark, progressive constriction of homeostatic reserves that occurs with aging (i.e., decreased ability over time to deal with external perturbations or stresses). All systems age and become dysregulated, with magnification of adverse processes. He accentuated that age effects on parameters of health vary significantly and increase with advancing age; further, the contribution of behavioural and environmental factors on health is not fully understood. He further cautioned that the challenge in identifying the best normal aging model in humans should not be underestimated, nor the role played by selection bias in published aging studies.

Dr. Alibhai noted his focus on B-cell and T-cell lines, which interact significantly in the immunological system. Dr. Alibhai stated that much that is known in this area is derived from extensive in vitro work. In vivo research into immunology is clearly more difficult to obtain; problematically, in vitro handling may lead to altered and destabilized cellular functions. Some in vitro findings have limited clinical relevance or unverified implications. Finally, animal model findings are variably duplicated in human studies.
The immune system comprises both innate and adaptive or acquired immunity (broken down into cellular and humoral components). Dr. Alibhai noted the artificiality of the distinction given the complexity of the B-cell and T-cell relationships in the setting of infection and other immune dysregulation syndromes.

Innate immunity is the earliest line of defense. Innate immunity offers rapid but incomplete defense against foreign attack until the slower but more definitive acquired immune response develops.

Dendritic cells are of key importance to initiating immune response and as antigen-presenting cells; they deliver activation signals to T-lymphocytes. Human studies have generally shown equivalent antigen-presenting ability in older as in younger humans, as well as equivalent ability to induce T-cell proliferation.

Next he spoke to the role of macrophages, which activate early in immune defense. There is evidence of impaired function with age, of consequence given their role in phagocytosis and intracellular killing, and as antigen-presenting cells to the rest of the body. With age there is both more nonspecific activation yet decreased capacity to produce tumour necrosis factor (TNF), interleukin (IL)-1, and nitric oxide (needed to inhibit tumour growth and stimulate immune defenses). Dr. Alibhai described them as functioning “in overdrive”; their dysfunction may contribute to delayed wound healing.

Dr. Alibhai then detailed the role played by natural killer (NK) cells, which kill target cells spontaneously without activation. Whether NK cell number or activity changes with age is unclear. To activate NK cells, higher levels of interferon a for maximal activation may be needed.

Finally, the complement system is important to the functioning of the innate immune system. Dr. Alibhai described this as an enzyme system that catalyzes other reactions, through cytolysis, activating the inflammatory cascade. The complement system exemplifies homeostenosis, as when an older animal is inoculated, the complement pathway does not arise with maximal efficiency.
The complement system itself is 20 interacting plasma proteins that constitute an enzyme system that defends against micro-organisms through cytolysis, opsonization, and activation of inflammation. There are slightly higher levels of certain components of complement with aging, but with bacterial infections complement levels do not rise in older adults, the consequence being a blunted response to infection.

Shifting focus to adaptive immunity, Dr. Alibhai defined the central players as B- (that is, bone marrow–derived) and T- (thymus-derived) lymphocytes. They recognize foreign substances based on peptide recognition. The thymus is the main location for T-cell development; 95% of thymocytes are eliminated in situ or via apoptosis. There is increasing dysregulation with aging: thymic involution begins at birth and undergoes dramatic involution by 90% by age 60, beyond which thymic hormones are no longer detectable in serum.

The key and primary defect with aging is loss of helper T-cell function (due to decreased antibody response, decreased capacity to expand under threat, and incomplete differentiation). T-cells’ proliferative response to mitogenic lectins is blunted; other examples of its dysregulation include exhibition of aberrant characteristics with aging. T-cells are more likely to initiate apoptosis upon activation in older adults and are replenished more slowly.

Moving on to B-cells, Dr. Alibhai stated that their major role is to produce antibodies as part of the humoral response. With aging, this response is impaired qualitatively and quantitatively. Older adults have a blunted response to immunization, with poorer antibody response. Natural antibodies decline with age through B-cell loss, and the frequency of antigen response in B-cells decreases—not only are there fewer cells but over time up to 30% become nonfunctional. Other key changes include an increase in nonspecific IgG production; further, B-cells may be chronically activated and exhibit other forms of dysregulation. There seems to be enhanced autoimmune activity with aging, with an increased frequency of autoantibodies against organ-specific and non-organ-specific antigens. The clinical significance of these autoantibodies remains contested.

Additionally, Dr. Alibhai mentioned immunologic change to the mucosal system. With the caveat that good study data are lacking, he mentioned there appears to be degrading mucosal integrity with age, and also likely defects in local antibody production.
Regarding altered allergenicity, it appears that IgE-mediated hypersensitivity reactions are less common with aging, but this remains a hypothesis. Serum IgE production declines with age, and there is deficient IL-4 production, among other forms of dysregulation.

With age there is increasing dysregulation in the cytokine system—a complex series of interacting pro-inflammatory and anti-inflammatory proteins that help to regulate the immune system—and key alterations involve IL-6 (Figure 1). The age-associated increase in IL-6 is a major cytokine derangement, Dr. Alibhai stated, and may parallel chronic inflammation; this leads to bone resorption, may play a role in Alzheimer’s disease, and may produce excess mortality in the medium term. IL-1 production is decreased with aging, and IL-2 production and responsiveness are blunted. He noted that it remains unclear which cytokine changes are key, as no one acts independently. Over time there is more T-cell than B-cell response to infection with age. Not all changes are attributable to aging per se, and subclinical disease and/or environmental factors likely play some role.

 

The clinical consequence is that older adults are more predisposed to infection but not overt immune deficiency. There is increasing risk of reactivation of dormant infection such as herpes zoster and mycobacterial infection. These risks are compounded by illness and malnutrition. Further, vaccinations are less effective and there is higher risk of parasitic infection.

Treatment options to reverse these aging changes are limited due to a paucity of high-quality, long-term studies, and safety and efficacy of potential therapeutic agents are not clearly established. Early evidence suggests the potential value of melatonin for increased antibody production, helper T-cell activity, and may be able to stimulate IL-2 release. Other data suggest that modified nutritional intake is associated with positive health correlates (e.g., enhanced immunity via increased intake of polyunsaturated fatty acids and vitamin E); further, there has been some benefit shown with modified immunization schedules (e.g., more numerous doses of hepatitis B vaccines in older adults) but larger studies are needed.

The next phase of the presentation concerned changes to the haematological system with age. Generally, concentrations of most blood constituents do not change with age. However, anaemia becomes increasingly common with older age but is not fundamentally age-related (body iron stores increase with age); instead, anaemia may be attributable to disease or other factors (e.g., subtle nutritional deficiencies). Haemoglobin levels may decline slightly with age, although this is still controversial. More importantly, the aged bone marrow cannot quickly respond to acute loss of blood. Thus it takes longer to correct acute anaemia by making new red blood cells. Dr. Alibhai reminded listeners that total white blood cell counts do not change with age, but response is blunted to stresses. Neutrophil and monocyte counts do not change with age, but lymphocyte counts decline slightly. With bacterial infections, there are paradoxical decreases in the number of and proliferative rate of neutrophil precursors, partly due to cytokine dysregulation. Older neutrophils are less able to migrate to the site of injury or generate antimicrobial oxidants in response to attack. Older lymphocytes are more vulnerable to radiation damage.

There may be some hypercoagulability and increased red blood cell viscosity with aging, but data are unclear.

Clinical implications of these haematologic changes include a higher predisposition among older adults to developing and sustaining anaemia in response to bleeding. He reiterated that anaemia is not due to aging and needs investigation. As for dangers of anaemia, he advocated that physicians beware of its association with fatigue, slower recovery after ADL disability, impaired executive function, depressive symptoms, increased hospitalization, and increased mortality. How much is causation versus correlation is an area of ongoing investigation.

Other clinical implications are that in individuals undergoing bone marrow suppression (e.g., with chemotherapy), colony stimulating factors (e.g., granulocyte colony-stimulating factor) are usually recommended for neutropenia prophylaxis in oncology settings.
In closing, he emphasized that most haematological indices do not change with age, and the noninvasive work-up for anaemia (ferritin, B12, RBC, folate, etc.) is equally sensitive and specific as in younger people. Dr. Alibhai drew particular attention to evidence that reticulocytosis is impaired with aging, that reticulocyte response to erythropoietin administration is blunted, and other bone marrow reserves are decreased in response to high demand.

The Impact of Anemia on Physical Function among Older Adults

Cinzia Maraldi, MD, Department of Clinicial and Experimental Medicine, Division of Internal Medicine, Gerontology, and Geriatrics, University of Ferrara, Ferrrara, Italy; Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida, Gainesville, FL, USA.
Marco Pahor, MD, Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida; Geriatric Research, Education and Clinical Center (GRECC), Malcolm Randall Veteran’s Affairs Medical Center, Gainesville, FL, USA.

Maintaining independence is one of the major goals in geriatric care, and identification of modifiable conditions that may promote the onset and progression of disability is of paramount importance in the clinical approach to the older patient. Anemia is key among those factors that may affect physical function in older adults. It is a common condition that appears to predict the onset of functional decline and disability in older adults. Early diagnosis of anemia and identification of its underlying causes is important not only in order to prevent the condition from worsening but also to prevent its associated poor health outcomes.
Key words: anemia, aging, disability, hemoglobin, functional decline.

A Case of Iron Deficiency Anemia

Please read "A Case of Iron Deficiency Anemia: Commentary" below

Anna Monias, MD, Erickson Retirement Communities, Oak Crest Village, Parkville, MD, USA.

Mr. WH is a 72-year-old-man who presented in April 2004 with a hematocrit of 21%. His previous hematocrit was 34% in February 2004. He complained of bright red blood per rectum and rectal pain secondary to external hemorrhoids. Mr. H was admitted with a presumed gastrointestinal bleed.
Mr. H’s past medical history is significant for bovine aortic valve prosthesis in 1997 secondary to aortic stenosis, Addison’s disease, hypocalcemia, seizure disorder, B12 deficiency, colon cancer with partial colon resection, and small bowel obstruction due to adhesions. Mr. H had chronic diarrhea secondary to bowel surgeries. His last colonoscopy was in 1997 and it revealed hemorrhoids. An esophagogastroduodenoscopy done at the time showed duodenitis.
The patient’s medications on hospital admission were as follows: calcium carbonate 500mg three times a day, vitamin B12 1000mcg I.M. monthly, divalproex sodium 750mg twice a day, hydrocortisone 25mg every 12 hours, vitamin D 100,000 IU every three months, phenobarbital 30mg every 12 hours, lasix 20mg by mouth daily, and potassium chloride 20m.e.q. daily. He has no known drug allergies.

The Anemia Institute for Research and Education: Treating Anemia Seriously

Durhane Wong-Rieger, PhD, President, Anemia Institute for Research & Education.

Anemia affects tens of thousands of Canadians, including many older people. While some types of anemia are relatively easy to diagnose and treat, complications such as chronic disease or complex medication regimes can often interfere with diagnosis and management of this condition.

The Anemia Institute for Research & Education (AIRE) is the first and only nonprofit organization in the world committed entirely to generating and sharing knowledge about anemia. AIRE supports patients in understanding anemia, its causes, effects and the available treatment options. The Institute partners with numerous patient and professional groups to facilitate patient education on anemia and blood safety and supply. Furthermore, through a yearly research grant competition, AIRE sponsors numerous anemia research studies. All in all, the Anemia Institute is working hard to ensure that anemia is treated seriously.

For Physicians: Anemia Guidelines for Primary Care
In a 2001 survey of family physicians across Canada, 90% of doctors indicated their interest in clinical practice guidelines on anemia for family practice. The Anemia Institute responded, initiating the development of Anemia Guidelines for Primary Care with MUMS Guidelines Clearinghouse (Medication Use Management Services), to be published in May 2003. The Anemia Guidelines is the fifth book in the Orange Book guideline series published by MUMS. This easy to use, peer-reviewed and fully-referenced book provides diagnostic and treatment guidelines for the full range of anemia conditions (see Table 1 for a selection of topics covered).

A limited number of complimentary copies of the Anemia Guidelines is available from AIRE. To order, please visit www.anemiainstitute.org and go to the Healthcare Professionals section.

For Your Patient: Anemia Educational Tools
The Anemia Institute's series of patient leaflets covers the most common types of anemia. Patient Educational Leaflets include:

• What is Anemia?
• What is Hemoglobin?
• Anemia & Nutrition
• Anemia & Iron Deficiency
• Anemia & Cancer
• Anemia & Kidney Disease
• Anemia & Surgery
• Anemia & Hepatitis C
• Anemia & HIV/AIDS
• Anemia & Children and Teens.

Anemia Awareness Week is the Institute's yearly campaign to raise awareness of anemia among the general public. This takes place each year during the last week of March. In March 2003, the public were invited to visit numerous hemoglobin screening clinics and anemia display booths in pharmacies and hospitals across Canada. Similar events are planned for Anemia Awareness Week next year, March 22&endash;26, 2004.

Research & Development Fund
The Anemia Institute Research & Development Fund supports research initiatives through a yearly, peer-reviewed grant competition. Projects currently funded include:

• the role of anemia and red blood cell substitutes in traumatic brain injury;
• new strategies to treat post-transplant anemia;
• anemia among the inner city homeless.

More information on the AIRE research grant process, including funding priorities and application procedures, can be found on the Internet at www.anemia-institute.org.