Those of you who read my column on a regular basis know that dementia is one of my particular interests, and that I am fortunate to be able to work in the Toronto Western Hospital Memory Clinic on a regular basis. Recently, I had the very stressful task of assessing an esteemed senior colleague for possible dementia. This was a reminder to me of how stressful it must be for those family members who come to our clinic wondering whether their loved one has dementia. I suspect the stress and anxiety I felt assessing a colleague were nothing compared to what the average spouse feels when a beloved partner is being assessed. It is very satisfying for me to state that our journal regularly includes articles on caregiver stress, and how the physician can help.

Even the most minor stress is exacerbated by lack of sleep. However, among people with dementia the risks involved in taking medications increase, and treating insomnia is very difficult. This important topic is addressed by Dr. Jason Strauss in his article “Insomnia in Older Adults with Dementia.” Another very distressing problem, “Hallucinations in Dementia” is addressed by a renowned expert, Dr. Jiska Cohen-Mansfield. In our car-based society, one of the difficult issues in dementia management is that of fitness to drive. The article “Practical Experience-Based Approaches to Assessing Fitness to Drive in Dementia” by Drs. Frank Molnar, Anna Byszewski, Mark Rapoport, and William Dalziel addresses this thorny problem. We all know the difficulty in managing a patient with dementia in hospital who becomes delirious, and this is an issue in long-term care as well. This major issue is addressed in the article “Preventing Delirium among Older Adults with Dementia,” by Dr. Donna Fick and Dr. Ann Kolanowski.

Our Cardiovascular column, “Diagnosis and Management of Heart Failure with Preserved Ejection Fraction in Older Adults” by Dr. George Heckman and Dr. Robert McKelvie, addresses a clinical syndrome that is most prevalent among older adults. We all rely to a great extent on our vision to make sense of the world surrounding us, but visual impairment is distressingly common among older people, so the article “Current Options in Low Vision Rehabilitation” by Dr. Samuel Markowitz is very relevant. Health safety experts often maintain that a well-educated patient is a major bulwark against medical error. Practical advice in this regard is given in the article “Educating the Older Adult in Over-the-Counter Medication Use” by Dr. Judith Glaser and Dr. Lydia Rolita.

Enjoy this month’s issue.
Barry Goldlist

Ann Kolanowski, PhD, RN, FAAN, Elouise Ross Eberly Professor of Nursing, The Pennsylvania State University, University Park, PA, USA.
Donna M. Fick, PhD, RN, GCNS-BC, Associate Professor of Nursing, The Pennsylvania State University, University Park, PA, USA.
Linda Buettner, PhD, LRT, CTRS, Professor of Recreation Therapy/Gerontology, Department of Recreation, Tourism, Hospitality Management, University of North Carolina, Greensboro, NC, USA.

Few clinicians have an educational grounding in the use of nonpharmacological therapies for people with dementia. In this article, we explore the utility of recreational activities as one nonpharmacological intervention that has demonstrated effectiveness for reducing the behavioural symptoms of dementia. The implementation of effective recreational activities involves three components: understanding the evidence for this approach; acknowledging the need to reduce medications that have the potential to interfere with activity effectiveness; and individualizing activities so that the maximum benefit from the intervention is obtained.
Key words: dementia, activities, nonpharmacological interventions, potentially inappropriate medications, individualized care.

Évaluation de l’aptitude à conduire chez les personnes atteintes de démence

Conférencier : Frank Molnar, M. Sc., MDCM, FRCPC, membre du personnel, service de gériatrie, Hôpital d’Ottawa; professeur agrégé, département de médecine, Université d’Ottawa; chercheur affilié, Institut de recherche en santé d’Ottawa; scientifique, Institut de recherche Élisabeth-Bruyère, Ottawa (Ontario).

Le D^r Frank Molnar, membre du réseau de chercheurs interdisciplinaires du programme CanDRIVE (The Canadian Driving Research Initiative for Vehicular Safety in the Elderly), a présenté les approches pratiques permettant d’évaluer l’aptitude à conduire un véhicule dans le cadre d’un diagnostic de démence.

La recherche du programme CanDRIVE
L’équipe de recherche du programme CanDRIVE, subventionné par les Instituts de recherche en santé du Canada (IRSC), a effectué des recherches substantielles et proposé d’importantes recommandations sur l’aptitude à conduire, en s’appuyant sur une double approche. Le premier objectif du groupe fut de trouver et de valider des outils de dépistage pour cette population de patients. Ce travail fondamental a nécessité la constitution d’une équipe nationale de recherche pour examiner les aspects médicaux de l’aptitude à conduire. Cette collaboration entre divers professionnels de la santé, qui a abouti à la mise en œuvre de tests comportant des valeurs seuils en fonction des données de groupe, a permis de passer au second volet de leur objectif : faciliter le réseautage et la transmission des savoirs (aboutissant à l’ajustement des valeurs seuils et à l’utilisation de résultats spécifiques pour éva-luer chaque patient). CanDRIVE va effectuer une grande étude prospective de cohortes pour suivre les aptitudes à la conduite d’adultes atteints de démence.

Alors que la recherche primaire en est à ses débuts, le D^r Molnar a précisé que les équipes de recherche de CanDRIVE s’attacheront à transmettre les connaissances acquises aux médecins. De plus, CanDRIVE aspire à tenir compte des opinions des cliniciens sur les recherches à effectuer.

L’étendue du problème
Bien que les conducteurs âgés soient généralement plus prudents que les cohortes plus jeunes, le taux d’accidents de véhicules motorisés par kilomètre parcouru en fonction de l’âge du conducteur augmente après l’âge de 80 ans. Ce décalage, principalement dû à l’accumulation de problèmes médicaux à un âge avancé, signifie que le nombre de collisions et de victimes va prendre de l’ampleur avec le vieillissement de la population. Les salles d’urgence auront à traiter un nombre croissant de personnes âgées victimes d’accidents de la route.

Les projections de Transport Canada jusqu’en 2026 indiquent que les accidents vont surtout augmenter chez les personnes âgées. Impliquées dans un accident, ces dernières ont une probabilité quatre fois plus élevée d’être grièvement blessées ou hospitalisées, et sont plus susceptibles d’être atteintes d’une incapacité permanente ou de décéder. Elles se réta-blissent également plus lentement. Les études ont montré que la majorité des personnes âgées victimes d’accidents de la route conduisaient le véhicule, et que la plupart des accidents impliquant des conducteurs âgés mettent en cause plusieurs véhicules et touchent des innocents. Le D^r Molnar a invité ses auditeurs à considérer que ce n’est pas une faveur que de permettre aux conducteurs âgés de conduire lorsqu’ils atteignent la limite de leur aptitude à le faire sans danger.

Ce n’est pas seulement un problème d’âge
La vaste majorité des conducteurs âgés sont des conducteurs prudents, a insisté le D^r Molnar, et CanDRIVE est sensible au fait que son travail pourrait contribuer à l’âgisme ou à l’alarmisme concernant les aînés au volant. Il a souligné que les troubles médicaux et les traitements médicamenteux sont la première cause de l’incompétence des conducteurs âgés, et que tout médicament peut contribuer au risque de collision. Les personnes âgées sont affectées de façon disproportionnée en raison de la polypharmacie.

Le D^r Moldar a déclaré explicitement qu’il est impossible d’associer de manière catégorique un danger à une maladie ou un trouble chronique précis. Ce ne sont pas les troubles qui sont dangereux, mais leur gravité ou leur instabilité, auxquelles s’ajoutent des doses élevées ou les changements de doses de médicaments. Les médecins ne peuvent pas prévenir chaque accident, mais ils sont bien placés pour identifier de nombreuses personnes susceptibles d’être dangereuses au volant. Les troubles médicaux ou les médicaments qui sont les plus corrélés à une diminution de l’aptitude à la conduite sont ceux qui modifient les capacités physiques, sensorielles, mentales ou émotionnelles.

La conduite met en jeu un ensemble complexe de capacités et d’attitudes cognitives, notamment des catégories d’action opérationnelles, tactiques et stratégiques. Les médecins ne peuvent pas évaluer correctement à 100 % une fonction altérée, en raison des limites de l’examen physique (conçu principalement pour détecter la présence de maladies, et non pour évaluer la fonction ou la sécurité) et du manque de temps adéquat dans un cadre clinique de première ligne. Par exemple, les décisions prises au volant reposent sur l’aptitude des conducteurs à faire des choix tactiques, assistant les décisions contextuelles en temps réel. Si des déficiences existent dans cette catégorie, elles sont souvent difficiles à dépister par le médecin. Les médecins peuvent difficilement éva-luer la capacité stratégique, à savoir les décisions prises avant de se mettre au volant. Aucun outil de dépistage ne sera jamais entièrement efficace pour prévenir tous les accidents de véhicules motorisés. La plupart des protocoles d’évaluation ne testent que des caractéristiques intrinsèques stables de l’aptitude à conduire. Les médecins peuvent ne pas détecter une maladie récente ou fluctuante, ou anticiper le discernement de leurs patients sur des facteurs extrinsèques comme la météo, les autres conducteurs, les conditions routières ou la sécurité d’une voiture.

Évaluation clinique : survol des enjeux
On peut cependant améliorer l’évaluation, et CanDRIVE cherche à attirer l’attention sur la question, car il est bien établi qu’une altération de la fonction cognitive augmente le risque d’accident avec responsabilité pour les conducteurs. Une étude de 2004 a révélé qu’il y a actuellement des dizaines de milliers de conducteurs âgés atteints de troubles démentiels en Ontario; en 2028, ils approcheront les 100 000.

Un diagnostic de démence ne signifie pas automatiquement une interdiction de conduire, a déclaré le D^r Molnar. Cependant, un tel diagnostic signifie que le clinicien doit demander si la personne conduit encore, et la sécurité de sa conduite doit être évaluée et établie. Les exigences provinciales en matière de déclaration varient, mais elles spécifient invariablement que le trouble doit être évalué et déclaré.

Les recommandations de l’Association médicale canadienne (AMC), « Évaluation médicale de l’aptitude à conduire : Guide du médecin » (7e éd.) rejoignent les déclarations consensuelles internationales qui reconnaissent les limites des données disponibles sur l’évaluation, mais recommandent les directives suivantes : 1) interdiction de conduite pour les personnes atteintes de démence modérée ou grave (AMC : démence modérée = 1 AVQ ou 2 AIVQ altérées par un problème cognitif); 2) évaluation individuelle des personnes qui présentent une démence légère; 3) suivi périodique obligatoire (tous les 6 à 9 mois); 4) évaluation complète au volant (la norme de référence en matière d’évaluation). Le Dr Molnar a émis l’avis que les recommandations de l’AMC devraient aller plus loin en ce qui concerne les AVQ : toute altération des AIVQ dans le domaine cognitif devrait entraîner automatiquement une évaluation de l’aptitude à conduire. En outre, il trouve que la règle d’un suivi tous les 6 à 9 mois n’est pas assez flexible, et conseille une approche personnalisée (p. ex. : une évaluation tous les 3 mois dans le cadre d’une maladie évoluant rapidement).

Le D^r Molnar a attiré l’attention sur le fait que, malgré l’existence de protocoles d’évaluation clairs (comment utiliser le MMSE, le test de l’horloge, la partie B du test des tracés, etc.), aucune indication n’est fournie au médecin sur la façon d’appliquer de tels tests. Par exemple, comment réagir à différents scores, quelles valeurs seuils utiliser, et quelles erreurs constituent automatiquement un échec? Ces questions font encore l’objet de débats. CanDRIVE a examiné des douzaines d’articles sur la démence et la conduite, mais n’a pas trouvé un seul test cognitif dont l’analyse s’appuie sur une valeur seuil validée. Les cliniciens travaillent dans un vide de données prouvées.

Une approche pour évaluer l’aptitude à la conduite
Les cliniciens doivent d’abord poser la question : « Est-ce que vous conduisez? » L’absence d’une telle vérification n’a pas protégé les cliniciens en procès, a averti le Dr Molnar. Ensuite, souvenez-vous que l’aptitude à la conduite repose sur un tableau clinique global, comprenant la cognition, le bilan fonctionnel, les capa-cités physiques, l’état de santé, le comportement et le dossier de conducteur du patient. Et puis, après les questions générales, réalisez des tests cognitifs spécifiques. Les renseignements corroborés par la famille peuvent être utiles, et le D^r Molnar a suggéré plusieurs pistes d’enquête qu’il vaut mieux aborder en l’absence du patient (Tableau 1). De plus, prenez en compte les états pathologiques qui, lorsqu’ils sont graves, mal contrôlés ou en évolution rapide, peuvent compromettre l’aptitude à la conduite (il a invité les cliniciens à se poser la question : « Est-ce que je monterais dans une voiture conduite par cette personne sur la foi de ces résultats? »). Le D^r Molnar a recommandé d’attacher la plus haute importance aux « 3 D » (démence, délire et dépression). Il a ensuite passé en revue les médicaments pouvant affecter la conduite (Tableau 2).

Il est essentiel de tester des domaines cognitifs spécifiques, comme le font les protocoles susmentionnés. Le jugement est apprécié par la réponse à des tests éva-luant la réaction à des situations dangereuses (comme le feu); les capacités visuo-spatiales sont testées grâce au MMSE et au test de l’horloge; la fonction exécutive est évaluée par les parties A et B du test des tracés, le test de l’horloge et le test de fluence verbale (nommer des animaux pendant une minute); et le temps de réaction peut être vérifié par le test de rattrapage de la règle lâchée. Dans le cas où les scores cognitifs se chevauchent ou ne sont pas clairs, le D^r Molnar a plaidé pour une trichotomisation sérielle (p. ex., conducteur vraiment dangereux, résultat incertain nécessitant d’autres tests et aucun souci pour la sécurité; figure 1).

Il a recommandé de commencer par le MMSE : les patients obtenant un score inférieur à 20 représentent probablement un danger au volant. Tous les tests mentionnés apportent des données précieuses; le test de rattrapage de la règle lâchée, bien que non validé, est important pour évaluer les réactions. De tels tests sont très utiles parce que les décréments du temps de réaction (qui n’est pas évalué lors de l’examen physique) ne deviennent souvent apparents qu’en dehors des tests, où les laps de temps se comptent en secondes. Néanmoins, la conduite implique des temps de réaction de l’ordre de la milliseconde.

Conclusion
Le D^r Molnar a terminé en insistant sur le fait qu’en cas de diagnostic de démence, il convient de s’interroger sur l’aptitude à conduire, et en faire une évaluation formelle et bien documentée. Les médecins peuvent effectuer une évaluation clinique approfondie de la sécurité au volant en 15 à 20 minutes. Si les cliniciens ne sont pas convaincus d’une telle sécurité, il convient d’orienter le patient vers des évaluations spécialisées ou des tests spécialisés sur route. En cas de démence, il faut réévaluer la sécurité au volant tous les 6 à 9 mois. Finalement, il a invité toute personne ayant des idées concernant l’évaluation de la conduite de les porter à l’attention du personnel de CanDRIVE par l’intermédiaire du site Web du programme (www.candrive.ca).

Nutrition et démence chez les personnes âgées

Conférencière : Carol Greenwood, Ph. D., professeure, département des sciences de la nutrition, Université de Toronto; chercheuse titulaire, unité de recherche appliquée Kunin-Lunenfeld, Baycrest Centre, Toronto (Ontario).

La D^re Greenwood a placé le thème de sa discussion sur la nutrition et la démence dans le contexte des considérations sur les influences environnementales constituant un risque de déclin cognitif et de démence. Même si la démence a d’importantes racines génétiques, les facteurs environnementaux jouent un rôle important dans son étiologie. Selon certaines études, ces facteurs sont associés à environ 60 % des cas de démence survenant après l’âge de 80 ans.

Habitudes alimentaires augmentant le risque de déclin cognitif
Pour bien comprendre le risque posé par les facteurs environnementaux, la D^re Greenwood a recommandé à ses auditeurs de porter attention au régime alimentaire sur une longue durée plutôt qu’à des cas particuliers d’apports alimentaires, bons ou mauvais. La connexion entre nutrition et démence repose sur l’idée sous-jacente que les neurones ont besoin d’apports nutritifs. Des changements nutritionnels entraînent des modifications du métabolisme neuronal. Une alimentation saine garantit la signalisation de l’insuline dans le cerveau, nécessaire à l’apprentissage et à la mémoire. Les cliniciens doivent encourager des habitudes alimentaires propres à maintenir les concentrations cérébrales de neurotrophines nécessaires à la plasticité synaptique impliquée dans la consolidation de la mémoire; de plus, une bonne alimentation et des apports nutritifs appropriés peuvent réduire l’inflammation et le stress oxydatif, et maintenir la capacité de la circulation cérébrale à fournir les nutriments essentiels au cerveau.

Des progrès dans ce domaine de recherche permettraient de contrer l‘isolationnisme qui marque parfois la perception des maladies chroniques. Le cerveau est fortement subordonné à la santé de l’organisme tout entier et une modification de l’alimentation peut exercer une influence directe sur des mala- dies liées au régime alimentaire, comme les maladies cardiovasculaires (MCV), le diabète de type 2 et la dépression.

De nombreuses études épidé-miologiques sur l’alimentation sont disponibles et indiquent qu’un apport calorique excessif engendre un stress oxydatif. La D^re Greenwood et ses collègues se sont penchés sur le rôle des apports en graisses. Un apport élevé en graisses, surtout saturées et polyinsaturées, accompagné d’un déficit en graisses oméga, est typique de l’alimentation nord-américaine. Des études ont montré que les régimes alimentaires faibles en fruits, en légumes, en céréales complètes et en huiles de poisson sont associés à un risque plus élevé de démence. Ce régime est également associé aux MCV, au diabète, à la dépression et à d’autres états pathologiques inflammatoires et chroniques. Les effets indésirables sur le cerveau ne sont pas simples, et il est probable que des mécanismes multiples sont impliqués; dissocier le rôle de la maladie chronique d’un impact direct sur la fonction cérébrale risque de donner une fausse idée de ces effets.

Les huiles de poisson constituent un bon exemple de la façon dont un nutriment particulier peut intervenir sur des voies neuronales multiples. Les études portant sur les huiles de poisson et le risque de démence ont eu du mal à isoler le rôle propre de ces huiles parce que, comme tous les nutriments, celles-ci ont de multiples effets sur l’organisme. Comme les graisses oméga font partie des recommandations alimentaires, la distinction entre le rôle soi-disant phy-siologique du nutriment et son rôle pharmacologique s’estompe. L’incorporation de graisses oméga dans un régime alimentaire holistique est une bonne approche, qui « stimule » le système. L’autre approche compte sur un impact pharmacologique important avec une stratégie de type « cibler et isoler » grâce à des suppléments alimentaires et un enrichissement nutritionnel (comme les œufs). Mais une telle approche néglige d’autres propriétés très précieuses des protéines de poisson.

De la même façon, des recherches sur les avantages cliniques associés à une exposition altérée aux antioxydants ont isolé des micronutriments et les ont fournis sous forme de suppléments alimentaires, ce qui a abouti à des données ambiguës. Cependant, on ne peut pas extrapoler les effets de cette consommation à ceux d’un régime alimentaire incorporant des micronutriments sur la base d’un apport nutritif mesuré en grammes par jour. L’approche ciblée oublie également que le cocktail nutritif complet est plus important (p. ex. : aspect synergique) que la consommation de chaque composé séparément. Les constituants alimentaires fonctionnent en bloc.

Il existe des enjeux pressants étant donnés les changements des marqueurs de santé à l’échelle de la population tout entière. Les personnes présentant une adiposité centrale (associée au développement du syndrome métabolique) sont des « bombes à retardement » de comorbidités. Les résultats de nouvelles études indiquent que l’obésité centrale autour de la cinquantaine augmente le risque de démence, indépendamment des comorbidités diabétiques et cardiovasculaires; les sujets présentant le degré le plus important d’obésité centrale triplent leur risque de déclin cognitif¹.

Le régime alimentaire méditerranéen
L’approche clinique de tels patients doit inclure un changement d’habitudes alimentaires, et les données probantes proviennent principalement du régime méditerranéen (Figure 1). Les effets bénéfiques sont directement liés à l’augmentation des apports en fruits, en légumes et en poisson, et à la réduction de la consommation de viande rouge. De récentes données en faveur de cette approche ont été fournies par une étude prospective de 2 258 sujets non atteints de démence en milieu communautaire à New York; mieux le régime méditerranéen était suivi, plus le risque de maladie d’Alzheimer (MA) était faible².

Le rôle du contrôle glycémique et du diabète de type 2
De plus en plus de données scientifiques laissent entendre que le diabète est en soi un facteur de risque de déclin cognitif, ce qui nécessite un contrôle glycémique draconien chez les patients hyperglycémiques.

Des études animales ont apporté des preuves de l’interrelation entre contrôle glycémique et démence, et la Dre Greenwood et ses collègues ont examiné l’effet des habitudes alimentaires typiquement nord-américaines sur la performance cognitive du rat, particulièrement sur l’apprentissage et la mémoire. Les bais-ses de performance étaient clairement associées à une consommation riche en graisses saturées : les rats soumis à ce régime étaient plus susceptibles d’avoir des performances aléatoires lors des tests.

Il reste à identifier quels aspects du régime riche en graisses saturées nuisent à la fonction cognitive, et à démêler ces effets de ceux du diabète. La D^re Greenwood a mentionné des études présentant les résultats d’une évaluation neuropsychiatrique habituelle de personnes âgées hyperglycémiques, qui examinait plus particulièrement la mémoire immédiate et différée (cette dernière faisant appel à la fonction hippocampique). Les résultats montrent que les personnes les plus insensibles à l’insuline réalisent la moins bonne performance. Avec l’âge, la perte de sensibilité à l’insuline est liée à une détérioration de la mémoire.

Maladie chronique et risque accru de démence
Les recherches actuelles indiquent de plus que la résistance à l’insuline peut excéder les effets de la consommation de graisses sur le déclin cognitif. Des études récentes s’appuyant sur l’imagerie structurelle éclairent la relation entre diabète et cognition. Une étude examinant la perte de la fonction hippocampique chez des sujets âgés non encore diagnostiqués pour un diabète de type 2, mais dont le contrôle glycémique est défaillant, a trouvé qu’un très mauvais contrôle glycémique était fortement associé à une atrophie hippocampique. De tels effets sont évidents chez les personnes dont le diabète est bien maîtrisé; à mesure que le diabète perdure et que les sujets perdent le contrôle métabolique et développent une hyper-cholestérolémie et une hypertension, l’atrophie se propage dans le cerveau et des lésions de la substance blanche se manifestent. Ce sont les composantes vasculaires du diabète, qui apparaissent plus tard au cours de l’évolution de la maladie.

La voie de signalisation de l’insuline est nécessaire à la mémorisation
La D^re Greenwood a fait observer que, bien que le cerveau ne soit généralement pas considéré comme un organe sensible à l’insuline, la densité cérébrale de récepteurs de l’insuline est élevée, et les voies de signalisation de l’insuline jouent un rôle intégral dans la consolidation de la mémoire. Ces voies sont perturbées chez les diabétiques. De telles associations avec les voies de signalisation de l’insuline sont importantes et peuvent expliquer les mauvaises performances de mémoire des personnes diabétiques par rapport à des non-diabétiques d’âge apparié, mais ce n’est pas une preuve irréfutable d’une contribution du diabète à la pathologie de la démence.

La D^re Greenwood a suggéré qu’une perturbation des voies de signalisation de l’insuline contribue sûrement à cette pathologie. L’enzyme de dégradation de l’insuline est l’enzyme clé impliquée dans la dégradation du peptide Ab, qui favorise le développement des plaques de la ma-ladie d’Alzheimer. Cette enzyme est régulée à la baisse dans le cerveau des diabétiques, ce qui ralentit la dégradation du peptide Ab. De plus, de fortes concentrations périphériques d’Ab entravent l’exportation d’Ab, et constituent donc un risque élevé d’accumulation du peptide Ab. Les diabétiques présentent également des niveaux élevés de cytokines inflammatoires, engendrant une accumulation pathologique du peptide Ab et des réponses inflammatoires correspondantes. La cascade inflammatoire du peptide Ab favorise la formation de plaques.

Des études portant sur des sujets au diabète bien maîtrisé, mais porteurs d’un polymorphisme génétique au niveau du gène codant pour le facteur de nécrose des tumeurs (TNFa), corroborent cette idée. Ces individus sont moins à même de fabriquer le TNFa et de déclencher des réponses inflammatoires. Les porteurs de SNP (polymorphisme nucléotidique) obtenaient de meilleurs résultats aux tests et leur baisse de performance était moindre. Le rôle des cytokines inflammatoires en terrain diabétique fait selon toute vraisemblance partie intégrante de l’entretien de la santé cérébrale, a déclaré la D^re Greenwood.

Des perturbations de la voie de signali-sation de l’insuline peuvent également contribuer à la formation des enchevêtrements neurofibrillaires. En particulier, le taux de GSK-3, une enzyme atténuée par la voie de signalisation de l’insuline, peut augmenter chez les diabétiques. La GSK-3 est importante, car elle augmente la phosphorylation de la protéine tau associée à la formation des enchevêtrements neurofibrillaires, et ces derniers sont plus nombreux en terrain diabétique ou obèse. L’accumulation d’enchevêtrements signale le passage d’une perte normale de fonction à une pathologie. En conséquence, certains ont avancé que la MA est la séquelle cérébrale du diabète, ce que réfute la D^re Greenwood, bien qu’elle pense que la maladie se manifeste plus rapidement dans ce contexte.

Habitudes alimentaires favorisant le bien-être cognitif
La principale recommandation alimentaire au patient diabétique doit être de consommer des aliments à faible indice glycémique. Les études portant sur la performance cognitive postprandiale ont constaté que les fonctions de mémorisation et de remémoration étaient altérées après une consommation d’aliments à glucides simples. Il semble que ce soit la sécrétion de cortisol induite par l’insuline, et non les modifications de la glycémie, qui est la clé de cette réponse. L’augmentation du cortisol entraîne des effets problématiques sur l’hippocampe, dont certains sont liés au stress oxydatif. En outre, les diabétiques bénéficiant d’un bon apport en antioxydants souffrent de baisses cognitives moindres. La clé réside dans un contrôle glycémique minutieux afin de minimiser l’agression diabétique répétée au cours de la journée.

Conclusion
La D^re Greenwood a fait observer que les modifications du régime alimentaire des personnes âgées peuvent s’interpréter comme une recommandation de perte de poids, et ce risque est souvent avancé comme objection aux modifications alimentaires. Aucune ligne directrice claire ne permet au médecin de décider quand cesser d’encourager la perte de poids, qui est corrélée à un risque de fragilité chez la personne âgée. La meilleure approche pour minimiser la fragilité, a-t-elle conseillé, c’est d’améliorer les apports nutritifs tout en faisant plus d’exercice physique. Une approche plus ferme des habitudes alimentaires est nécessaire, étant donné que l’incidence du diabète et du syndrome métabolique évolue, notamment en raison du vieillissement de la génération du baby-boom. La D^re Greenwood a averti son auditoire que les forces contribuant à l’augmentation de la démence sont largement sous-estimées, et qu’il est grand temps d’instaurer des modifications du mode de vie.

Bibliographie

1. Whitmer RA, Gustafson DR, Barrett-Connor E, et al. Central obesity and increased risk of dementia three decades later. Neurology 2008;71:1057-64.
2. Scarmeas N, Stern Y, Tang MX, et al. Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 2006;59:912-21.

Nutrition and Dementia among Older Adults

Speaker: Carol Greenwood, PhD, Professor, Department of Nutritional Sciences, University of Toronto; Senior Scientist, Kunin-Lunenfeld Applied Research Unit, Baycrest Centre, Toronto, ON.

Dr. Carol Greenwood contextualized her discussion’s theme of nutrition and dementia as contributing to considerations of the environmental influences posing risk for cognitive decline and dementia. While dementia has important genetic roots, a large causative factor is environmental exposure. In cases of disease onset at >80 years of age, studies have suggested that ~60% relates to this factor.

Dietary Patterns that Increase Risk of Cognitive Decline
To understand the risk mediated by environmental exposure, she recommended that listeners focus on chronic diet rather than on instances of good or poor intake. The connection between nutrition and dementia relates to the underlying idea that neurons require nutritional support; altered nutrition equates to altered neuronal metabolism. Sound nutrition maintains brain insulin signaling, needed for learning and memory. Clinicians should aim to promote dietary habits that maintain brain neurotrophin levels, which support synaptic plasticity needed for memory consolidation; further, good diet and appropriate nutrient intake can reduce inflammation and oxidative damage, and maintain the cerebrovasculature’s capacity to supply essential nutrients to the brain.

Advances in this area of research could help to remediate an isolationist philosophy that can pervade viewpoints on chronic disease. The brain is highly sensitive to the health of the body, and through dietary modification it is possible to exert direct impact on diet-associated conditions such as cardiovascular disease (CVD), type 2 diabetes, and depression.

Many epidemiologic studies on diet are available, indicating that excess caloric intake leads to oxidative stress. Dr. Greenwood and colleagues have examined the role of fat intake. High fat intake, particularly of saturated and polyunsaturated fats, along with a dearth of Omega fats, are typical of the North American diet. Studies have shown that diets low in fruits, vegetables, whole cereal grains, and low in fish oils are associated with higher risk of dementia. This diet profile also associates with CVD, diabetes, depression, and other inflammatory and chronic disease states. The adverse effects on the brain are not simple, and multiple mechanisms are likely involved; separating the role of chronic disease from a direct impact on brain function would distort the effects.

Fish oils exemplify how individual nutrients can modulate multiple neuronal pathways. Studies involving fish oils and dementia risk have found the individual role hard to isolate because they, as all nutrients, have multiple effects in the body. As the Omega fats are incorporated into dietary recommendations the so-called physiologic role of the nutrient versus the pharmacologic role blurs. Incorporating the Omega fats on a wholistic nutritional basis is the sound approach, one that “nudges” the system. The other seeks to exert a large pharmacological impact with a “targeting and isolating” approach through supplements or food enrichment (e.g., eggs). Such an approach overlooks other aspects of fish protein that are valuable.

Similarly, investigations of health outcomes associated with altered antioxidant exposure have isolated micronutrients and supplied them in supplemental form, producing equivocal data. However, measuring the effects of this consumption should not be extrapolated to the effects of a dietary pattern that incorporates micronutrients on a grams per day nutritional intake. The targeted approach also overlooks that the full nutritional cocktail is more important (e.g., the synergistic aspect) than consuming any one individual compound. Food constituents work together.
These are pressing issues given the population-wide changes in health markers. Individuals with central adiposity (associated with development of the metabolic syndrome) are a “time bomb” of comorbidities, she stated. New study results suggest that central obesity in midlife increases dementia risk independent of diabetes and cardiovascular comorbidities; individuals with the greatest degree of central obesity bear a threefold increase of cognitive decline.¹

The Mediterranean Diet
The needed clinical approach for such patients supports changing eating patterns, and the burden of evidence points toward the Mediterranean diet (Figure 1). The beneficial effects relate directly to increased fruit, vegetable and fish intake and reduced red meat consumption. Recent evidence for the approach was provided by a prospective study of 2,258 community-based nondemented individuals in New York; those with higher adherence to the Mediterranean diet had lower risk for Alzheimer’s disease (AD).²

The Role of Type 2 Diabetes and Glycemic Control
Increasing evidence suggests that diabetes per se appears to be a risk factor for cognitive decline, necessitating aggressive glycemic control in hyperglycemic patients.

Evidence for the interrelationship of glycemic control and dementing illness has been drawn from animal studies, and Dr. Greenwood and colleagues have investigated the effect of typical North American dietary patterns on cognitive performance in rats, specifically on learning and memory. Performance decrements were clearly associated with high saturated fat consumption; rats fed this diet were most likely to show random/chance performance in testing.

The task is to identify which qualities of the high saturated fat diet compromise cognitive function, and to disentangle these effects from diabetes’ effects. Dr. Greenwood cited studies with standard neuropsychiatric assessment results of hyperglycemic older adults, looking specifically at immediate and delayed recall (the latter calls on hippocampal function). Results show those more insensitive to insulin exhibit worse performance. With age, lost insulin sensitivity relates to impaired memory function.

Chronic Disease and Enhanced Dementia Risk
Current research further suggests that insulin resistance may outweigh the effects of fat consumption on cognitive decline. Recent studies using structural imaging have cast light on the relationship between diabetes and cognition. One study investigating loss of hippocampal function in older individuals not yet diagnostic of type 2 diabetes but with compromised glucose control found that worse control strongly associated with hippocampal atrophy. Such effects are evident among well-controlled diabetic individuals; as diabetes endures, and individuals lose metabolic control and develop hypercholesterolemia and hypertension, atrophy disperses throughout the brain, and the presence of white matter lesions becomes evident. These are the vascular components of diabetes appearing later in its course.

Insulin Signaling Is Needed for Memory Processing
Dr. Greenwood observed that while the brain is not often considered an insulin-sensitive organ, it has a high density of insulin receptors, and insulin signaling pathways play an integral role in memory consolidation. These insulin signaling pathways become disrupted in the setting of diabetes. These associations with the insulin pathway are important and may explain why the diabetic individual has poor memory performance relative to an age-matched nondiabetic, but it is not clear indication that diabetes contributes to dementia pathology.

It likely does both, Dr. Greenwood argued. The key enzyme involved in degradation of Ab protein promoting development of AD plaques is the insulin degrading enzyme, which is down-regulated in the brains of those with diabetes, slowing Ab degradation. In addition, the Ab export is impaired due to high levels of Ab in the periphery, leaving them at high risk of Ab accumulation. Diabetics also have higher levels of inflammatory cytokines, producing a disease state of Ab accumulation and corresponding inflammatory responses. The Ab inflammatory cycle facilitates plaque formation.

Studies featuring individuals with well-controlled diabetes but carrying a genetic polymorphism to tumour necrosis factor (TNF)a support this view. Such individuals are less able to manufacture TNFa and launch inflammatory responses. Those carrying the single nucleotide polymorphism (SNP) have performed better on testing and showed fewer decrements in performance. The role of inflammatory cytokines in the context of diabetes is likely integral to the maintenance of brain health, Dr. Greenwood stated.

Disturbances to the insulin signaling pathway may also contribute to the development of neurofibrillary tangles. Specifically, GSK-3, an enzyme dampened by the insulin signaling pathway, may be increased in those with diabetes. GSK-3 is important because it increases phosphorylation of the tau protein associated with development of neurofibrillary tangles, which appear in greater levels in the diabetic/obese state. The accumulation of tangles signals the move from normal loss of function into pathology. Correspondingly, some have argued that AD is the brain sequelae of diabetes, and while Dr. Greenwood expressed her disagreement, she thinks the disease occurs more rapidly in this setting.

Dietary Patterns that Promote Cognitive Well-Being
The focus of dietary recommendations for the diabetic patient should be on low-glycemic index food intake. Studies that have investigated postprandial cognitive performance found that after consuming simple carbohydrate foods, degraded processing and recall function results. It appears that insulin-induced cortisol secretion, and not changes in blood glucose, are key to this response. Increased cortisol exerts problematic effects in the hippocampus, some of which relate to oxidative stress. Further, diabetic individuals with sound antioxidant intake experience fewer decrements in cognition. The key is careful glycemic control to minimize the diabetic insult occurring repeatedly throughout the day.

Conclusion
Dr. Greenwood observed that the risk of appearing to recommend weight loss to an older population is often raised as an objection to dietary modification. There are no clear guidelines as to when physicians should stop encouraging weight loss, which is correlated with frailty risk with advancing age. The best approach to minimizing frailty, she advised, is improved nutritional intake combined with increased exercise. A more aggressive approach to dietary patterns is required, given that the incidence of diabetes and the metabolic syndrome are changing, especially as baby boomers age. Dr. Greenwood advised listeners that the pressures driving dementia upward are vastly underestimated, and now is the time to implement lifestyle modifications.

References

1. Whitmer RA, Gustafson DR, Barrett-Connor E, et al. Central obesity and increased risk of dementia three decades later. Neurology 2008;71:1057-64.
2. Scarmeas N, Stern Y, Tang MX, et al. Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 2006;59:912-21.

Assessment of Fitness-to-Drive in Persons with Dementia

Speaker: Frank Molnar, MSC, MDCM, FRCP(C), Staff, Division of Geriatric Medicine, The Ottawa Hospital; Associate Professor, Department of Medicine, University of Ottawa; Affiliate Investigator, The Ottawa Health Research Institute; Scientist, The Elisabeth Bruyere Research Institute, Ottawa, ON.

Dr. Frank Molnar, a member of the network of interdisciplinary investigators for the Canadian Driving Research Initiative for Vehicular Safety in the Elderly (CanDRIVE), reviewed practical approaches to assessing fitness to drive in the setting of a dementia diagnosis.

CanDRIVE Research
The Canadian Institutes of Health Research (CIHR)-funded CanDRIVE research team has worked to produce substantive research and recommendations on fitness to drive via a two-pronged approach. First, the group has aimed at deriving and validating screening tools for this patient segment. This pillar of their work has involved building a national research team to examine medical aspects of fitness to drive in conjunction with an array of health professionals (leading to the development of tests with cut-offs based on group data), in order to pursue the second pillar of their purpose: facilitating networking and knowledge translation (leading to adjusting cut-offs and using specific findings to assess individual patients). CanDRIVE will conduct a large prospective cohort study that tracks fitness to drive among adults with dementing illness.

While the primary research is in its infancy, Dr. Molnar explained that the CanDRIVE research teams will focus on disseminating their acquired knowledge to physicians. Further, CanDRIVE aims to incorporate input from clinicians on what they should be looking at.

The Scope of the Problem
While older drivers are generally safer when compared to younger cohorts, the rate of motor vehicle crashes per km driven according to driver’s age increases beyond age 80. This shift, due primarily to the accumulation of medical illnesses in late age, means the net number of collisions and casualties will soar with an aging populace. Emergency rooms will treat an increasing number of older crash victims.

Projections through 2026 from Transport Canada show that crashes will rise primarily in older groups. An older person involved in a crash has a fourfold higher likelihood of being seriously injured or hospitalized; has a higher risk of becoming permanently disabled or dying; and takes longer to recover. Studies have shown that the majority of crash-injured seniors were driving the vehicle, and that most of the crashes involving older drivers are multivehicle and involve innocents. Dr. Molnar asked listeners to consider that they are not doing older drivers a favour by letting them drive when they reach the limit of their ability to do so safely.

The Problem Is not Age Alone
The vast majority of older drivers are safe drivers, Dr. Molnar insisted, and CanDRIVE is sensitive to the concern that their work contributes to ageism or alarmism about seniors at the wheel. He emphasized that medical conditions and medications are the primary cause of older drivers’ incompetence, and any medication can contribute to collision risk. Older people are affected disproportionately due to polypharmacy.

Dr. Molnar explicitly stated that no disease or chronic condition can be isolated as categorically risky. It is not the presence but severity and/or instability of conditions, plus high doses and/or changing doses of medications, that are perilous. While physicians cannot prevent every accident, they are well-placed to detect many persons who are at risk for unsafe driving. Qualities of medical conditions or medications most correlated with impaired driving capacity are those that alter physical, sensory, mental, or emotional abilities.

Driving recruits a complex set of cognitive capacities and behaviours, including operational, tactical, and strategic categories of action. Doctors cannot correctly assess impaired function 100% due to limitations of the physical exam (which is primarily designed to detect presence or absence of disease, not to assess function or safety) and the inadequate time available in front-line clinical settings. For example, tactical maneuvering is involved in decisions drivers make on the road—it supports real-time contextual decisions. Impairments in this category are often hard for doctors to catch. Strategic capacity refers to decisions made before getting on the road, which is difficult for doctors to assess. No screening tool will ever be completely effective for screening for all motor vehicle crashes. Most assessment protocols only test stable intrinsic features of driving ability. Doctors may miss new or fluctuating illness. Further, physicians cannot anticipate patients’ judgment of extrinsic factors such as weather, other drivers, road conditions, or a car’s safety.

Clinical Assessment: An Overview of the Issues
Assessment can be improved, however CanDRIVE seeks to galvanize attention on this issue as it is well-documented that cognitive impairment puts drivers at increased risk of at-fault crashes. A 2004 study found that currently there are tens of thousands of older drivers with dementing illnesses in Ontario; by 2028, the figure will approach 100,000.

A diagnosis of dementia does not automatically mean no driving, Dr. Molnar stated; however, a diagnosis of dementia means that the clinician must ask if the person is still driving, and driving safety must be assessed and documented. Provincial reporting requirements vary but uniformly state that the condition must be assessed and reported.

The Canadian Medical Association’s (CMA) guidelines, “Determining Medical Fitness to Operate Motor Vehicles” (7th ed.), joins international consensus statements that recognize the limitations of available data on assessment but recommend that: one, those with moderate to severe dementia should not drive (CMA: Moderate = 1 ADL or 2 IADLs impaired due to cognition); two, that individual assessment should be performed for those with mild dementia; three, that periodic follow-up is required (every 6-9 months); and four, the “gold standard” is comprehensive on-road assessment. Dr. Molnar opined that the CMA guidelines should go further in terms of ADLs—any single IADL impairment due to cognition should trigger an assessment of fitness to drive. Further, he finds the 6-9 month follow-up rule insensitive and advises an individualized approach (e.g., assessing every 3 months in the setting of rapidly progressing disease).

Dr. Molnar cautioned that while clear assessment protocols are given (e.g., for using the MMSE, Clock Drawing, Trails B), no guidance is provided as to how physicians should apply such tests. For example, how to respond to different scores, what cut-offs to use, and which errors equal automatic failure remain under debate. CanDRIVE has examined dozens of dementia and driving articles, and was unable to find one cognitive test that was analyzed via a validated cut-off. Clinicians are working in an evidence-based vacuum, Dr. Molnar stated.

An Approach to Assessing Fitness to Drive
Clinicians must inquire, “Do you drive?” Failure to verify has not protected clinicians in litigation, Dr. Molnar advised. Two, recall that driving capacity depends on a global clinical picture, including the patient’s cognition, function, physical abilities, medical conditions, behaviour, and driving record. Then, follow general questions with specific cognitive tests. Corroborative information from the family can help, and Dr. Molnar suggested several areas of inquiry that are best asked when the patient is not in the room (Table 1). Further, review medical conditions that when severe, poorly controlled, or changing rapidly can compromise capacity to drive (he suggested clinicians ask themselves, “Would I get in a car with this person based on these findings?”). Dr. Molnar recommended that the “3 Ds”— dementia, delirium, and depression— are most important to consider. He then reviewed medications that could affect driving (Table 2).

The key intervention is to test specific cognitive domains, as with the aforementioned protocols. Judgment is assessed by the test response to dangerous situations (e.g., fire); visuospatial ability is tested with the MMSE and clock drawing; executive function is assessed with Trails A and B, clock drawing, and 1-minute animal naming; and reaction time can be verified with the ruler drop test. In the case of overlapping/unclear cognitive scores, he argued for serial trichotomization (e.g., clearly unsafe, uncertain with further testing required, no concerns regarding safety), as shown in Figure 1.

He advised that the MMSE is the best place to start; patients scoring under 20 are likely unsafe to drive. All areas of testing mentioned yield valuable data; the ruler drop test, while not validated, is important in assessing reaction. Such tests are valuable because decrements of reaction time (which is not tested in the physical examination) often only become apparent outside of testing when lapses involve seconds. However, driving involves the need for reactions on a millisecond scale.

Conclusion
Dr. Molnar closed with emphasizing that if dementia is diagnosed, driving must be asked about, formally assessed, and documented. Physicians can perform a comprehensive driving safety clinical evaluation in approximately 15 to 20 minutes. If clinicians are unsure of safety, refer to specialized assessment or specialized on-road testing. In dementia, reassess driving safety every 6 to 9 months. Finally, he encouraged those with any ideas about driving assessment to bring them to the attention of CanDRIVE staff via their website (www.candrive.ca).

Aleksandra Klimkowicz-Mrowiec, PhD, Department of Neurology, University Hospital Cracow, Poland.

Stroke and dementia are major health problems affecting older people. Cerebrovascular disease is the second-leading cause of dementia after Alzheimer’s disease, the third- leading cause of death, and one of 10 leading causes of physical disability. In parallel with the increased prevalence of stroke in aging populations and the decline in mortality from stroke, the rate of diagnosed poststroke dementia has increased, causing a growing financial burden for health care systems. This article discusses the epidemiology, etiology, and determinants of poststroke dementia and outlines the search for a suitable treatment.
Key words: dementia, stroke, cognition, risk factors, cognitive impairment.

Catherine Agbokou, MD, MSc, Service de Psychiatrie Adulte, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France.
Emmanuel Cognat, MD, Service de Psychiatrie et de Psychologie Médicale, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris, France.
Florian Ferreri, MD, MSc, Service de Psychiatrie et de Psychologie Médicale, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris, France.

Differentiating between Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) is a difficult issue for many clinicians. To date, these diseases share most of their clinical, neuropathological, and management features. Therefore, PDD and DLB are considered by some authors to be the two extremities of a single spectrum disease named Lewy body diseases. Nevertheless, specific diagnostic criteria now exist for each disease and specific diagnosis remains of interest in clinical practice. In this article, we summarize features and diagnostic criteria of both PDD and DLB, compare them, and examine their treatment options.
Key words: Parkinson’s disease dementia, dementia with Lewy bodies, Lewy body disease, movement disorders, dementia, treatment.

Click here to view the entire report from the 4th Canadian Colloquium on Dementia

Dementia and Depression: The Importance of Recognizing their Relationship

Speaker: Dr. Kristine Yaffe, MD, Associate Professor, Department of Psychiatry, Neurology and Epidemiology; Co-director of the Clinical and Translational Sciences Training Program, University of California, San Francisco; San Francisco, CA, USA.

Dr. Kristine Yaffe, of the University of California, San Francisco and San Francisco VA Medical Center, sought to shed light on the co-occurrence of depression and dementia, which are commonly encountered by practitioners caring for aging adults. Cognitive impairment affects up to one-third of older adults. Similarly, depression appears frequently and can co-occur with dementia. Both affect quality of life, and contribute to increased morbidity and mortality among this population segment.

Why, Dr. Yaffe asked, might they go together? Patients presenting with symptoms of major depression often experience altered cognition as an effect of the mood disorder, and, similarly, depressive symptoms can accompany dementia as part of the disease. This is particularly the case in dementia with Lewy Bodies and frontotemporal dementia, but symptoms can appear in the setting of Alzheimer’s disease (AD) as well. Depression may not only be a reaction to cognitive problems but a risk factor for later cognitive impairment.

The depressive symptoms that tend to co-occur with deteriorating cognition include deficits in executive functioning and multitask domains, as well as inability to focus or retain new information. Processing speed is affected. However, on testing, memory impairment is often not registered and is not a hallmark of the paired conditions.

Dr. Yaffe stated that this constellation is recognized and tends to be termed pseudodementia. She questioned the value of the term, as the entity is not really “pseudo” and seems to call into question the validity and veracity of the patient’s experience. On the contrary, the symptoms are very real but not necessarily permanent. A careful cognitive evaluation is required; further, cognitive testing should be repeated subsequent to treating the depression.

Rather than thinking in terms of or aiming for clear-cut diagnosis, she encouraged listeners to think of patterns of disease expression. The focus must, however, remain on the particular individual and the uniqueness of his/her case.

Depressive Symptoms in the Setting of Cognitive Impairment
The general constellation Dr. Yaffe suggested that clinicians be aware of is marked by a general slowing down. She noted that typical depressive symptoms can differ in the setting of cognitive impairment; dysphoria, rather than major mood symptoms, is the hallmark. Other symptoms to watch for among older patients include loss of interest in usual activities and decreased social interaction.

Regarding the validity of currently available testing scales, Dr. Yaffe considered the commonly used dementia scales to be of value in the setting of mild and moderate dementia (Mini-Mental State Exam score ≥15). In advanced dementia, the scales are of diminished utility. Further, she claimed that the commonly used Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for depression are not very useful in this setting and advocated using the National Institutes of Mental Health Criteria for Depression in Alzheimer’s Disease (NIMH-dAD) criteria (Table 1). These are not dissimilar to DSM-IV but are less stringent—roughly, one major symptom is required, plus two others, for a positive diagnosis. She reminded listeners that the fifth revision of the DSM is forthcoming and new criteria are to be expected. Currently, the NIMH-dAD is a more sensitive scale and a better assessment tool when dealing with co-occurring dementia and depression.

Dr. Yaffe noted that many patients with dementia present with depressive symptoms. It is important to assess for depressive symptoms in dementia as they may bear on both the symptoms of and prognosis for the cognitive state. These patients are at double risk: they are vulnerable to greater functional decline and greater mortality. Neither condition is benign and both are treatable.
Depression may also be a risk factor per se for cognitive decline. Dr. Yaffe advocated watchfulness in the setting of geriatric depression, as patients should be monitored for signs of dementia. In her clinical practice, she will refer depressed older individuals for neuropsychiatric testing as they are at increased risk (by a factor of two to three times) for developing cognitive problems. Research has suggested that in the presence of three to five symptoms of depression, there is a doubling of risk of cognitive decline. This may be due to changes in cortisol; or, it could be an early symptom of neurodegeneration.

It is possible to see structural brain changes in imaging in dementia. Classically, three things appear: one, nothing, in some cases; two, numerous white matter changes, often in the frontal subcortical region, relating to the executive impairment (bringing vascular dementia to the fore); and three, hippocampal atrophy. Given the last, it is unsurprising, she stated, that individuals go on to develop cognitive difficulties. Functional imaging findings often include frontal hypometabolism (in depression), and classic temporal-parietal hypometabolism (in AD).

Treating Depression Co-Occurring with Dementia
As for treatment approaches, when treating geriatric depression in the setting of mild to moderate cognitive impairment, she noted that most pharmacotherapeutic options prescribed for younger adults, such as the selective serotonin reuptake inhibitors (Figure 1), also work in the older population, with the caveat that one must be vigilant regarding comorbidities and any relevant background medical conditions. Research has suggested that sertraline is of good utility in this patient segment. She noted that the sertraline studies and other relevant studies concerning the co-occurrence of the disorders have found that mood improves but the cognitive deficits tend to remain untouched. In her experience, Dr. Yaffe finds the impairment improves but does not disappear.
As for nonpharmacological treatments, cognitive behavioural therapy (CBT) can be helpful, even in vascular depression. The best strategy involves CBT plus pharmacological therapy. Among aging adults assisted by a caregiver, caregiver education is a key element of the therapy that should aim to redress any misconceptions or negative attitudes about the disorders from which the patient is suffering. Patient support groups are also of high value. While electroconvulsive therapy has been found to have efficacy in the setting of geriatric depression, note that it can cause increased confusion or other altered functioning.

Conclusion
Dr. Yaffe closed with some thoughts about the nature of the relationship between dementia and cognitive deficits. What stems from what, which of the two should be seen as a prodrome, and other key questions lack clear answers. What is clear, she noted, is that these conditions are not benign, they tend to co-occur, and recognizing this is among the key pearls she hoped to impart. Patients need to be followed closely, and their depression needs aggressive treatment.

Click here to view the entire report from the 4th Canadian Colloquium on Dementia

Idiopathic Normal Pressure Hydrocephalus

Speaker: Dr. Norman Relkin, MD, PhD, Director, Cornell Memory Disorders Program; Associate Professor of Clinical Neurology and Neuroscience, Weill Cornell Medical College; Associate Attending Neurologist, NewYork-Presbyterian Hospital, New York, NY, USA.

Dr. Norman Relkin discussed idiopathic normal pressure hydrocephalus (NPH), a disease commonly termed “reversible dementia.” Dr. Relkin formally defined NPH as “a condition characterized by chronic nonobstructive enlargement of the cerebral ventricles in association with progressive disturbances of gait and balance, cognition, and/or urination.” These form the so-called classic triad of NPH disturbance (Figure 1).

Dr. Relkin suggested that the triad’s shortcoming lies in its lack of universality, as the qualitative and quantitative expression of these symptoms varies. Nonetheless, the entity is often regarded as an ideal diagnosis, given these symptoms’ general applicability. Further, NPH is detectable on imaging and responds to surgical treatment with generally good long-term outcomes. However, NPH also lacks a gold standard of pathological criteria and does not respond to drug therapy (acetazolamide has been tried unsuccessfully, Dr. Relkin noted). Further, response to surgery can be inconsistent, and treatment involves a high rate of morbidity.

Diagnosing Normal Pressure Hydrocephalus
The Classic Triad
Clinical signs and symptoms, supplemented by radiologic findings, are the primary means of identifying patients with NPH. Dr. Relkin observed that researchers are working to identify biological markers for the disease in enhanced quantitative brain imaging, but integrating biomarkers into the differential diagnosis remains a future possibility.

Dr. Relkin urged his audience to be aware that the NPH-associated clinical triad is likewise not ideally reliable. One study found that, on diagnosis, ~50% of patients had the classic triad. Gait is the most reliably recognized symptom of NPH. Given that the triad is an imperfect diagnostic construct, he advised clinicians to be aware of the partial presentation of these symptoms: for example, urinary urgency is more common than frank incontinence in early stages of the disease. Overall, NPH-related disturbances may be subtle and not obviously progressive, but should be persistent.

Radiographic Evidence
Controversy lingers regarding the value of radiographic results for NPH, and, overall, there are no completely reliable quantitative measurements. The primary finding associated with NPH is atrophy. However, atrophy findings do not allow the clinician to rule out lookalike syndromes when investigating for NPH; the syndrome most commonly confused with NPH is aqueductal stenosis. Imaging characteristics of NPH include disproportionate ventriculomegaly, increased callosal angle, doming of the lateral ventricle, enlargement of the temporal horns, and expansion of the diameter of the third ventricle, often with a bowed appearance of that ventricle.

Dr. Relkin advised that cerebrospinal fluid (CSF) flow void symptoms and brain diffusivity measurements are not clear diagnostic indicators. Currently, inspection is the standard. Dr. Relkin addressed whether there is a way to distinguish the enlargement of temporal horns in NPH from that enlargement seen in Alzheimer’s disease (AD)-associated hippocampal atrophy. The hippocampus and parahippocampal folds do become more prominent in AD and can help differentiate atrophy from hydrocephalus. These areas take on a smooth, rounded contour in AD, and this can be a useful sign in some patients for distinguishing these two entities. However, Dr. Relkin advised, these can be comorbid diseases.

Features of Gait Abnormality
Gait abnormalities (incorrectly called gait apraxia) remain the best feature for recognizing NPH. Dr. Relkin advised that clinicians be alert to signs of slowed movement, decreased step height, inadequate upward angulation of the foot, diminished stride length, reduced shoulder counter-rotation relative to the pelvis, as well as increased step width and foot rotation angles. Of particular note is that patients will require 3-4 steps to perform a 180-degree turn. He emphasized that a qualitative and quantitative evaluation of gait and posture should be carried out in every case of suspected NPH.

Urinary Disturbances
Urologic evaluation may assist in differential diagnosis. Urinary disturbance, he stated, is the least consistently observed component of the NPH triad. There will be increased urinary frequency and urgency, as well as urinary incontinence (but not fecal, he noted). It is important to ask if there is nocturia, claimed Dr. Relkin. The gait disorder may impede toileting.

Cognitive Impairment
On cognitive evaluation, the hallmarks of NPH are slowed cognition, dysexecutive syndrome, visuospatial deficits, and behavioural changes. Testing may assist in assessing baseline mental status and response to treatment.

Other Signs and Symptoms Associated with Normal Pressure Hydrocephalus
Other findings indicative of NPH include increased head circumference, syncopal episodes, altered sleep architecture, and the development of systemic hypertension. The latter may occur 1-2 years prior to the onset of frank symptoms.

Symptoms Not Associated with Normal Pressure Hydrocephalus
Findings one would not expect in the case of NPH include papilledema, meningismus, headache, seizures (except post-shunt), or lateralized deficits. Dr. Relkin reminded listeners that the differential diagnosis is lengthy, and NPH symptoms need to be considered in light of overlapping symptomatology with lookalike syndromes (Table 1).

Given the lack of clarity around the signs associated with NPH, Dr. Relkin and colleagues worked to develop consensus criteria that were published in 2005.¹ They sought to define the probably, possible, and unlikely classifications for NPH based on history, brain imaging, clinical findings and physiologic criteria. Their recommendations appear in Table 2. The criteria given do not apply to a review of shunt responsiveness.

Dr. Relkin also discussed guidelines for cerebrospinal fluid drainage in the assessment of suspected NPH. The lumbar puncture tap test should involve the drawing of at least 40-50 cc’s of fluid. Gait and cognitive testing should follow within an hour of completing the tap. Continuous or intermittent draining will require hospital admission. Higher-volume drainage is more predictive of shunt responsiveness, he noted; further, a negative tap test does not preclude shunt reponsiveness.

Treatment
Programmable shunts are the new standard. They permit the opening pressure of the valve to be altered and can help to optimize treatment, but they add complication and cost. This cost is saved on the lower rates of re-operation. Complications of the shunt are the major drawback; the programmable shunt malfunction rate is 20%. Programmable shunts are part of an evolving and improving treatment process, Dr. Relkin claimed.

Conclusion
Dr. Relkin reminded listeners that NPH is one of the truly reversible causes of dementia if detected early. New technologies for diagnosis and treatment are improving disease outcomes.

Reference

1. Marmarou A, Bergsneider M, Relkin N, et al. Development of guidelines for idiopathic normal-pressure hydrocephalus: introduction. Neurosurgery 2005;57(3 Suppl):S1-3.