Yes / Objectives: To determine whether individual goal-oriented cognitive rehabilitation (CR) improves everyday functioning for people with mild-to-moderate dementia. Design and methods: Parallel group multi-centre single-blind randomised controlled trial (RCT) comparing CR added to usual treatment (CR) with usual treatment alone (TAU) for people with an ICD-10 diagnosis of Alzheimer’s, vascular or mixed dementia and mild-to-moderate cognitive impairment (MMSE score ≥ 18), and with a family member willing to contribute. Participants allocated to CR received ten weekly sessions over three months and four maintenance sessions over six months. Participants were followed up three and nine months post-randomisation by blinded researchers. The primary outcome was self-reported goal attainment at three months. Secondary outcomes at three and nine months included informant-reported goal attainment, quality of life, mood, self-efficacy, and cognition, and study partner stress and quality of life. Results: We randomised (1:1) 475 people with dementia; 445 (CR=281) were included in the intention to treat analysis at three months, and 426 (CR=208) at nine months. At three months there were statistically-significant large positive effects for participant-rated goal attainment (d=0.97, 95% CI 0.75 to 1.19), corroborated by informant ratings (d=1.11, 0.89 to 1.34). These effects were maintained at nine months for both participant (d=0.94, 0.71 to 1.17) and informant ratings (d=0.96, 0.73 to 1.2). The observed gains related to goals directly targeted in the therapy. There were no significant differences in secondary outcomes. Conclusions: Cognitive rehabilitation enables people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy. / National Institute for Health, Health Technology Assessment Programme, Grant/Award Number: 11/15/04

Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a cerebrospinal fluid shunt. It has been suggested that INPH has similar pathophysiological mechanisms as cerebrovascular disease, but the vascular risk factor (VRF) profile of INPH patients has not been assessed using a modern epidemiological approach. The cognitive symptoms of INPH resemble the symptoms of depression, but the prevalence of depression among INPH patients is unknown. In addition, few studies investigate the impact of shunting on the quality of life (QoL), and no study has investigated the impact of comorbidity on QoL in INPH patients. The objective of this dissertation was to present the VRF profile of INPH and to investigate the hypothesis that INPH may be a subgroup of vascular dementia. Additional objectives were to assess the prevalence of depression in INPH patients and to investigate the impact of shunting and comorbidities on QoL in INPH. In the first cohort, the prevalence of possible INPH was assessed through clinical and radiological examinations in patients with a transient ischemic attack (TIA), consecutively admitted to the same hospital during 2006-2008. In the second cohort, VRFs, vascular disease and QoL were analysed in INPH patients consecutively shunted 2008-2010 in five out of six neurosurgical centres in Sweden. Patients remaining after inclusion (n=176, within the age-span 60-85 years and not having dementia) were compared to population-based age- and gender-matched controls (n=368, same inclusion criteria as for the INPH patients). Assessed VRFs were: hypertension, diabetes, obesity, hyperlipidemia, psychosocial factors (stress and depression), smoking, alcohol intake, physical activity and, dietary pattern. Cardiovascular, cerebrovascular and peripheral vascular disease as well as QoL were also assessed. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG and, blood samples. In the first cohort, 4% of the TIA patients had clinically and radiologically verified INPH. In the second cohort, VRFs were overrepresented among the INPH patients compared with the controls. The VRFs independently associated with INPH were: hyperlipidemia (Odds ratio (OR): 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), obesity (OR: 5.4, 95%CI: 2.5-11.8) and, psychosocial factors (OR: 5.3, 95%CI: 3.2-8.9). When adding the VRFs that were overrepresented in INPH, although not independently (physical inactivity and hypertension), these six VRFs accounted for 24% of the INPH cases in the elderly population (population attributable risk %: 24). Depression was overrepresented in shunted INPH patients compared to the controls (46% vs. 13%, p<0.001) and the main predictor for low QoL was a coexisting depression (p<0.001). In conclusion, the results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH and indicate that INPH may be subgroup of vascular dementia. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for quality of life should be included in the work-up of INPH patients. The effect of targeted interventions against modifiable VRFs and anti-depressant treatment in INPH patients should be evaluated. / Idiopatisk normaltryckshydrocefalus (INPH, från engelskans ”idiopathic normal pressure hydrocephalus”) är en neurokirurgiskt behandlingsbar demens. Behandlingen är att operera in en shunt som dränerar cerebrospinalvätska från ventriklarna. Det har föreslagits att INPH skulle kunna orsakas av liknande patofysiologiska mekanismer som vid cerebrovaskulär sjukdom, men den vaskulära riskfaktorprofilen hos INPH-patienter har aldrig undersökts i en modern epidemiologisk studie. De kognitiva symtomen vid INPH påminner om symtomen vid depression, men prevalensen av depression hos INPH-patienter är okänd. Få studier undersöker hur shuntning påverkar livskvalitet och ingen studie har undersökt hur komorbiditet påverkar livskvaliteten vid INPH. Syftet med den här avhandlingen var att undersöka den vaskulära riskfaktorprofilen hos INPH-patienter samt att utforska hypotesen att INPH skulle kunna vara en undergrupp till vaskulär demens. Ytterligare ett syfte med avhandlingen var att undersöka hur många INPH-patienter som har depression samt undersöka hur shunting och komorbiditet påverkar livskvalitet vid INPH. I den första kohorten undersöktes kliniska och radiologiska fynd som tydde på INPH hos de patienter som blivit diagnostiserade med en TIA (från engelskans: transient ischemic attack) 2006-2008 på Norrlands Universitetssjukhus i Umeå. I den andra kohorten undersöktes konsekutivt shuntade INPH-patienter 2008-2010 från fem av sex neurokirurgiska kliniker i Sverige. De patienter som inkluderades i studien (n=176, ålder: 60-85 år, ej dementa) jämfördes med köns- och åldersmatchade kontroller från normalpopulationen (n=368, samma inklusionskriterier som för INPH-patienterna). De riskfaktorer som undersöktes var: hypertension, hyperlipidemi, diabetes, fetma, psykosociala faktorer (stress och depression), rökning, alkohol, fysisk aktivitet och diet. Även kardiovaskulära och cerebrovaskulära sjukdomar undersöktes, liksom perifer vaskulär sjukdom samt livskvalitet. Datainsamling skedde genom frågeformulär, kliniska undersökningar, mätningar, EKG och blodprov. I den första kohorten hade 4% av TIA-patienterna kliniskt och radiologiskt verifierad INPH. I den andra kohorten var vaskulära riskfaktorer överrepresenterade hos INPH-patienterna jämfört med iv normalpopulationen. Hyperlipidemi (OR: 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), fetma (OR: 5.4, 95%CI: 2.5-11.8) och psykosociala faktorer (OR: 5.3, 95%CI: 3.2-8.9) var associerade med INPH oberoende av kön, ålder och de andra riskfaktorerna. Hypertension och fysisk inaktivitet var också associerade med INPH, dock inte oberoende av övriga riskfaktorer. Sammanlagd PAR% (från engelskans: population attributable risk %) för de här sex riskfaktorerna var 24%. INPH-patienterna hade depression i högre utsträckning än kontrollerna (46% vs. 13%, p<0.001), och depression var den viktigaste prediktorn för låg livskvalitet. Resultaten tyder på att vaskulär sjukdom och vaskulära riskfaktorer är involverade i den patofysiologiska mekanismen vid INPH. INPH kan vara en undergrupp till vaskulär demens. En fullständig riskfaktoranalys och screening för depression bör ingå i den preoperativa utvärderingen såväl som i forskning på INPH-patienter, och ett mått på livskvalitet bör införas. Effekten av riktade insatser mot såväl vaskulära riskfaktorer som depression vid INPH bör utvärderas.

The aim of this thesis was to study the biomarker homocysteine and other novel potential vascular risk factors for dementia. In an out-patient based study of a cohort of 926 consecutive subjects referred to our Memory Unit during 1996―2000, serum-folate was lower and total plasma homocysteine (tHcy) and serum methyl malonate were higher in subjects being prescribed with B12. In the subgroup diagnosed with dementia and with a positive family history of dementia, tHcy was higher than in the subgroup diagnosed as non-demented. It is necessary to supplement subjects with vitamin B12 deficiency with B12, but our results indicate that it is not sufficient with B12 alone because this gives rise to intracellular folate deficiency. We also found indications of a genetic component in dementia because tHcy was higher in the group with a positive family history of dementia. These findings prompted further studies of homocysteine metabolism. The frequency of mutations in the gene for folate receptor-α (FOLR-1), and the fibrinolytic pattern in dementia and non-dementia were studied in the two cohorts DGM (n=300) and AS (n=389). The DGM cohort is a consecutive series of subjects attending our Memory Care Unit for investigation of suspected cognitive problems or dementia between 2003 - 2007. The AS (= active seniors) cohort comprises retired, apparently healthy subjects from central Sweden, actively participating in study circles. A rare haplotype in the FOLR-1, with mutations in two nearby loci, was discovered, possibly associated with lower serum-folate and higher tHcy concentrations and was more frequent in the DGM group. The transport of folate to the CSF was studied in the DGM-cohort. Dementia with a vascular component was associated with a lower CSF to serum folate ratio indicative of reduced transport of folate to the CSF and further to the brain. The vascular endothelial derived fibrinolytic markers tPA, tPA/PAI-1-complex, and vWF were not only higher in vascular dementia (VaD) but also in Alzheimer’s Disease (AD) when compared to the AS group. The impaired fibrinolytic activity in both vascular dementia and in AD is a novel finding, signifying a vascular component in the development of dementia. In conclusion we found that both hereditary and nutritional background factors were linked to dementia and furthermore that a dysregulated fibrinolysis was linked to both VaD and AD.

Quantitative magnetic resonance imaging (MRI) was used to assess global and regional cerebral volumes in patients with a clinical diagnosis of subcortical vascular dementia (VD) and Alzheimer’s disease (AD). Whole brain volume, cerebrospinal fluid volume, volumes of the temporal, frontal and parietal lobes, the cerebellum and the amygdala-hippocampus complex were determined using a personal computer-based software. Seventeen patients with VD, 22 patients with AD and 13 healthy controls were included. Analysis of covariance using age as covariate demonstrated significant mean differences between controls and dementia groups with respect to all morphological parameters. However, apart from the volume of the cerebellum no significant volumetric differences were found between VD and AD. These results indicate that MRI-based volumetry allows differentiation between AD or VD from normal controls and that measurement of cerebellar volume may be of use to separate vascular and degenerative dementia. However, since the distribution of cerebral atrophy in both dementia groups is very similar, it is suggested that the atrophic changes are not specific to the underlying cause but rather reflect the selective vulnerability of neuronal structures. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

It is emerging that the brain’s vasculature consists of a highly spatially heterogeneous network; however, information on how various vascular characteristics differ between brain regions is still lacking. Furthermore, aging studies rarely acknowledge regional differences in the changes of vascular features. The density of the capillary bed is one vascular feature that is important for the adequate delivery of nutrients to brain tissue. Additionally, capillary density may influence regional cerebral blood flow, a parameter that has been repeatedly correlated to cognitive-behavioural performance. Age-related decline in capillary density has been widely reported in various animal models, yet important questions remain concerning whether there are regional vulnerabilities and what mechanisms could account for these regional differences, if they exist. Here we used confocal microscopy combined with a fluorescent dye-filling approach to label the vasculature, and subsequently quantified vessel length, tortuosity and diameter in 15 brain regions in young adult and aged mice. Our data indicate that vessel loss was most pronounced in white matter followed by cortical, then subcortical gray matter regions, while some regions (visual cortex, amygdala, insular cortex) showed little decline with aging. Changes in capillary density are determined by a balance of pruning and sprouting events. Previous research showed that capillaries are naturally prone to plugging and prolonged obstructions often lead to vessel pruning without subsequent compensatory vessel sprouting. We therefore hypothesized that regional susceptibilities to plugging could help predict vessel loss. By mapping the distribution of microsphere-induced capillary obstructions, we discovered that regions with a higher density of persistent obstructions were more likely to show vessel loss with aging and vice versa. Although the relationship between obstruction density and vessel loss was strong, it was clear obstruction rates were insufficient to explain vessel loss on their own. For that reason, we subsequently used in vivo two-photon microscopy to track microsphere-induced capillary obstructions and vascular network changes over 24 days in two areas of cortex that showed different magnitudes of vessel loss and obstruction densities: visual and retrosplenial cortex. Surprisingly, we did not find evidence for differences in vessel pruning rates between areas, as we would have expected. Instead, we observed brain region-specific differences in recanalization times and rates of angiogenesis. These findings indicate that age-related vessel loss is region specific and that regional susceptibilities to capillary plugging and angiogenesis must be considered to explain these differences. Altogether, this work supports the overarching hypothesis that regional differences in vascular structure and function contribute to a regionally heterogeneous phenotype in the aging brain. / Graduate

Le fardeau vasculaire (présence de maladies vasculaires et/ou cérébrovasculaires) est associé à une augmentation des troubles cognitifs chez les personnes âgées, ainsi qu’à un plus haut risque de démence vasculaire (DV) et de démence de type Alzheimer (DTA). Un nombre restreint de travaux a porté sur l’impact du fardeau vasculaire sur la cognition des personnes avec trouble cognitif léger (TCL). Pourtant, les personnes avec TCL représentent une population d’intérêt puisqu’elles sont à haut risque d’évoluer vers une démence. Cette thèse comprend trois articles de revue qui visent à exposer les connaissances entourant la santé vasculaire et la cognition des personnes âgées et trois articles empiriques (Chapitres 5, 6, 7). La première étude empirique traite de l’impact du fardeau vasculaire sur la cognition des personnes TCL et a comme objectif de spécifier quelles fonctions cognitives sont affectées par le fardeau vasculaire et dans quelle mesure le fardeau vasculaire influence l’hétérogénéité des TCL (Chapitre 5). Dans le cadre de la deuxième étude, nous avons examiné l’intégrité des processus stratégiques et non stratégiques de mémorisation des TCL avec et sans fardeau vasculaire, afin d’évaluer si ces processus diffèrent quantitativement et qualitativement entre ces deux groupes (Chapitre 6). Enfin, dans la troisième étude nous avons évalué les capacités d’association (binding) ainsi que la résistance à l’interférence des personnes TCL, les liens entre ces processus mnésiques et différents marqueurs cérébraux en plus des facteurs permettant de prédire l’évolution vers une démence (Chapitre 7). Les résultats présentés dans cette thèse appuient l’hypothèse selon laquelle le fardeau vasculaire influence le profil cognitif des TCL. Dans un premier temps, nous avons montré que le fardeau vasculaire est associé à une atteinte exécutive plus importante chez les TCL (Chapitre 5). De plus, nos résultats suggèrent que le fardeau vasculaire influence la classification clinique de ces derniers, puisque ceux dont le fardeau est élevé répondent davantage aux critères de TCL amnestique domaine multiple (trouble de mémoire plus au moins un autre déficit cognitif) tandis que ceux sans fardeau répondent davantage aux critères de TCL amnestique domaine unique (trouble isolé de la mémoire). Dans un deuxième temps, nous avons montré des différences dans la nature des processus mnésiques atteints chez les TCL avec et sans fardeau vasculaire (Chapitre 6). Alors que les premiers présentent une atteinte prédominante des processus stratégiques de mémorisation, les seconds présentent une atteinte des processus stratégiques et non stratégiques de mémorisation. Lorsque seuls les résultats des TCL ayant évolué vers une démence sont analysés, le patron d’atteinte est similaire puisque les TCL vasculaires sont quantitativement moins touchés que les TCL non-vasculaires au niveau des processus non-stratégiques de mémorisation. Enfin, tant les TCL qui progressent vers une démence que les TCL qui restent stables après un suivi de trois ans éprouvent tous des difficultés de mémoire associative et sont sensibles à l’interférence proactive (Chapitre 7). De plus, le fardeau vasculaire est associé à la sensibilité à l’interférence alors que le volume hippocampique est associé aux difficultés de mémoire associative. Enfin, nos résultats indiquent que les TCL qui éprouvent des difficultés de mémoire associative sont plus à risque d’évoluer vers une démence que les TCL ne présentant pas ces mêmes difficultés. De façon globale, les résultats de cette thèse révèlent que le fardeau vasculaire joue un rôle important dans l’hétérogénéité des TCL. / Vascular burden (presence of vascular diseases and/or cerebrovascular diseases) increase cognitive deficits in older adults and have been associated with vascular dementia and Alzheimer’s diseases. However, only a few studies have examined the impact of vascular burden on cognitive functioning in persons with mild cognitive impairment (herein referred to as MCIs). Individuals with MCI are a target population for research since they are at high risk of developing dementia. Understanding the factors that influence MCIs cognition is thus a priority. This thesis aims to identify the impact of vascular burden on MCI’s cognition. First, a summary of the literature concerning vascular health and cognitive functioning in the elderly is presented here (Chapters 1, 2, 3 and 4). Then, three studies that represent the core of this thesis are exposed. The first one aims to identify which cognitive functions are affected by vascular burden in MCIs (Chapter 5). In the second one, we assess strategic and non strategic memory processes in MCI with and without vascular burden (Chapter 6). Finally, in the last study, we assess binding and sensitivity to proactive interference in MCIs who progress to dementia, and MCIs who remain stable in a three-year follow-up (Chapter 7). This latter study also assesses which brain changes influence binding and interference capacity in MCIs and which factors predict progression to dementia. Results of this thesis first revealed that vascular burden plays an important role in cognitive heterogeneity of MCIs. First, MCIs who present a high vascular burden have more executive deficits. Second, those same MCIs run a greater risk of being clinically classified as amnestic multiple domain MCIs (memory impairment plus impairment in at least one cognitive domain, whereas MCIs with no vascular burden run a greater risk of being classified as amnestic single domain MCIs (isolated memory impairment) (Chapter 7). In the second article of this thesis, we showed that MCIs with vascular burden have memory impairment restricted to strategic memory processes. When only the results of MCIs who progressed to dementia were analysed, a similar pattern of memory impairment was found, since MCIs with vascular burden were less impaired in non strategic than strategic processes, whereas both processes were impaired in MCIs with no vascular burden (Chapter 8). Finally, MCIs who progressed to dementia, and those who remained stable after a three-year follow-up, showed binding difficulties and vulnerability to proactive interference. This difference was particularly evident when only MCI progressors were compared to healthy controls. In summary, vascular burden plays a role in the cognitive heterogeneity of MCI.

No description available.

No description available.

Verhaltensstörungen bei Demenz sind von zentraler klinischer Bedeutung. Zur Beurteilung solcher Phänomene liegen eine Anzahl standardisierter Beobachtungsbögen vor. Problematisch sind diese Skalen im Hinblick auf ihre Reliabilität bei der Anwendung durch Angehörige und Pflegende. Wir schlagen daher die aktometrische Darstellung von motorischer Aktivität, wie sie etwa aus der Schlafforschung bekannt ist, vor. In dieser Dissertation wurde zunächst die Reliabilität und konkurrente Validität der Messung von motorischer Unruhe bei Demenz mittels eines aktometrischen Gerätes untersucht. Die Ergebnisse zeigen, dass die aktometrische Messung von Verhaltensstörungen eine valide und reliable Methode auch bei schwerer Demenz darstellt. Im zweiten Teils dieser Arbeit wurde unter quasiexperimenteller Kontrolle von Modulatoren der circadianen Rhythmizität Unterschiede der circadianen Rhythmik zwischen vaskulärer Demenz und Demenz vom Alzheimer-Typ untersucht. Dabei konnte gezeigt werden, dass es bei Patienten mit Demenz vom Alzheimer-Typ und bei Patienten mit vaskulärer Demenz in Abhängigkeit von der motorischen AktivitŠt zu einer charakteristischen Phasenverschiebung der circadianen Rhythmik kommt. Dieser Zusammenhang ist jedoch bei Alzheimer-Demenz, bei der von einer neurobiologischen Störung des suprachiasmatischen Nukleus ausgegangen werden kann, stärker ausgeprägt. Dieses Befundmuster unterstützt theoretische Modelle der circadianen Rhythmik und ihrer Störung bei Demenz und legt nahe, dass der suprachiasmatischen Nukleus bei Demenz vom Alzheimer-Typ eine zentrale Rolle bei der circadianen Regulation des Verhaltens einnimmt. / Behavioural signs and symptoms in dementia are of central clinical significance. There are a number of standardised rating scales available for the assessment of motor phenomena in dementia. However, there is no objective method of assessing these symptoms. In addition, the reliability of these scales, especially when used by caregivers from within families, has been questioned. In order to overcome this flaw, we propose the use of an actometric device for assessing behaviour motor symptoms in dementia. In the first part of this dissertation we assessed the reliability and the concurrent validity of an actometric device against two behavioural scales. Results show satisfactory validity and good reliability of this method. In the second part of this dissertation, we reanalysed data from our validation study, investigating whether the pattern of circadian rhythm disturbances is different in patients suffering from Alzheimer disease and patients suffering from vascular dementia, controlling experimentally for the severity of behaviour disturbances. With regards to circadian motor activity, we found increased nocturnal activity and fragmentation of diurnal rhythm in both groups. In patients showing an equal severity of behaviour disturbances, the phase-delay of the rest-activity rhythm was delayed in patients with Alzheimer disease as compared to patients with vascular dementia. These findings suggest that, in Alzheimer disease, structural changes in the SCN might induce disturbance in the circadian pacemaker, leading to a phase shift in the circadian rhythm. The differential pattern of rhythm disturbance found in this study could be indicative of different processes involved in sleep disorders in the dementias.

La dépression (caractérisée ou subsyndromique) est fréquente tout au long de la vie et les démences sont des pathologies fréquentes du sujet âgé. Une association longitudinale entre la dépression ou les symptômes dépressifs et la démence a été rapportée. Cependant, le sens de cette association demeure incertain et ses mécanismes pathogéniques selon l’âge de l’apparition des manifestations dépressives sont largement méconnus. Les facteurs de risque vasculaires sont associés à la démence et une comorbidité vasculaire est également retrouvée chez le sujet âgé dépressif. L’hypothèse qu’un ou des facteurs de risque cardiovasculaires constitue(nt) l’ultime dénominateur commun des troubles de l’humeur et de démences devrait être vérifié. L’objectif de cette thèse était d’étudier les liens entre la pression artérielle, la dépression et la démence. Dans un échantillon de 9294 sujets âgés de 65 ans et plus (Etude 3C), non institutionnalisés, suivis pendant 4 ans, nous avons retrouvé une association entre les symptômes dépressifs sévères à l’inclusion et le risque de démence (en particulier vasculaire) incidente. A l’opposé, les antécédents dépressifs n’augmentaient pas le risque de démence. Nos analyses transversales indiquaient une pression artérielle plus basse chez les sujets dépressifs comparés aux sujets non dépressifs. Pour terminer, l’association entre les symptômes dépressifs sévères et la démence n’était pas médiée par l’hypertension artérielle. Nos résultats indiquent que les symptômes dépressifs semblent constituer une expression non cognitive de la phase prodromale de la démence plutôt que d’en être un facteur de risque. L’explication d’une pression artérielle plus basse chez les sujets dépressifs comparés aux sujets non dépressifs n’est pas univoque. Une pression artérielle basse pourrait conduire à une hypoperfusion cérébrale, corrélée aux lésions de la substance blanche dans les régions les plus sensibles aux modifications du flux sanguin cérébral et dont l’altération est associée aux manifestations dépressives et cognitives. Ce travail offre de nouvelles perspectives de définition des groupes de population à haut risque de démence, et des perspectives de recherche sur les mécanismes biologiques liant la pression artérielle et la dépression. D’un point de vu méthodologique, il met l’accent sur la nécessité des méthodes d’évaluation fiables et précises des cas pathologiques (dépressifs et déments), lesquels influencent réciproquement l’évaluation de chacun. / Depression is highly common throughout the life course and dementia is common in late life. Depression has been linked with dementia, yet the direction and pathological mechanisms of this association (whether depression is a prodromal feature or consequence of, or a risk factor for dementia) remains unclear. Vascular risk factors are associated to the risk of incident cognitive impairment and dementia and comorbid vascular disease is a feature of depression in latelife. Therefore, the hypothesis that vascular risk factors are the ultim denominator of psychological perturbations and dementia is to be verified. The aim of this work was to study the links between blood pressure, depression and dementia. In a cohort of 9294 community-dwelling elderly individuals aged 65 years and over, participating to the longitudinal population-based 3 City Study, followed up for 4 years, we found an association between baseline depressive symptoms’ severity and the incident dementia risk (particularly of vascular type). Conversely, we found no association between history of depression and incident dementia. Moreover, our cross sectional analyses exhibited an inverse association between systolic and diastolic blood pressure values and depression. Overall, however, the association between depressive symptoms and dementia was not mediated by hypertension. These results indicate that depression is rather a prodromal symptom of vascular dementia than a risk factor for it. The explanation for the inverse association found between blood pressure values and depression is not straightforward. Low blood pressure may lead to cerebral hypoperfusion found to be associated with white matter lesions in cerebral regions vulnerable to alterations of cerebral blood flow, and associated with cognitive impairment and depression. This work offers the opportunity for the definition of group of populations at high risk to develop dementia, vascular one in particular. It also gives the perspective of research on the biological mechanisms linking blood pressure and depression. From a methodological point of view, it emphasizes the need for instruments assessing precisely and thoroughly these two conditions which influence the assessment of each other.