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Dementia, depression and parkinsonism: A frequent association in the elderly

Maria Cristina Polidoria,b,∗, Giuseppe Menculinic,d, Umberto Seninb and Patrizia Mecoccib aInstitut für Physiologische Chemie I, Heinrich-Heine Universität, Düsseldorf, Germany bIstituto di Gerontologia e Geriatria, Universitá di Perugia, Perugia, Italy cCasa di Ospitalitá per Anziani “Fontenuovo”, Fondazione O.N.L.U.S., Perugia, Italy dCasa di Riposo “Creusa Brizi Bittoni”, Cittá della Pieve, Perugia, Italy

Communicated by James Geddes

Depression and parkinsonism constitute two frequent findings in elderly demented patients. A large body of research, in- cluding epidemiological, retrospective, and prospective stud- ies have contributed to the understanding of complex and common situations in the elderly, in which depression, parkin- sonian signs, and cognitive impairment coexist. Many aspects regarding the “associated syndromes of dementia”, however, are still object of debate as well as under current active investi- gation. The recent dramatic aging of the population is leading to an increasing prevalence of neuropsychiatric comorbidi- ties. This is a problem of great clinical and socio-economical interest, because, when present in the same subject, depres- sion, parkinsonism-related motor impairment and cognitive impairment may not only act additively or synergistically in deteriorating the functional outcome of the patient, but also lead to their institutionalization. We observed that one half of institutionalized subjects in two nursing homes of Central Italy suffer from an associated syndrome dementia / parkin- sonism / depression, that these subjects are significantly more dependent than subjects hospitalized for the same reasons, and that their grade of depression or cognitive impairment is independent of which disease is diagnosed first. Depressed

∗Corresponding author: Maria Cristina Polidori, MD, Institut für Physiologische Chemie I, Heinrich-Heine Universiẗat, D-40225 Düsseldorf, Germany. Tel.: +49 211 81 12711; Fax: +49 211 81 13029; E-mail: [email protected].

mood, memory impairment and motor difficulties, however, are often underestimated in the elderly, being considered as “normal” aspects of the aging process. The aim of this re- view is to highlight the clinical relevance of the associated syndromes of dementia, in a way that early diagnosis and treatment of these pathologies are attempted.

Keywords: Parkinson’s disease, depression, aging, extrapyra- midalism

1. Introduction

Dementia, depression and parkinsonism represent among the most prevalent and disabling pathologies in aging [3,21,51]. According to the Early Identification of Alzheimer’s Disease and Related Dementias Panel, 5 to 10 percent of the US population aged over 65 years suffers from a dementing disorder, with the incidence doubling every five years after the age of 65, and with Alzheimer’s disease (AD) accounting for two thirds of all cases of dementia [21]. Depression is the most com- mon psychiatric disease in the population aged 65 years and over, reaching peaks of prevalence of more than 30 percent in the frail and disabled elderly [51]. The prevalence of Parkinson’s disease varies among differ- ent reports, from 31 to 328 per 100,000 persons, with the average annual incidence rate in the population be- tween 65 and 84 years being estimated, in Italy, almost 530 per 100,000 persons for parkinsonism and almost 327 for Parkinson’s disease [3].

The relationship between dementia, depression and parkinsonism in aging is a complex issue, not only be- cause it is very difficult to achieve a reliable estimate of the prevalence of each of these pathologies, but also because the coexistence of two or more of them is un- derestimated, and because the pathophysiology under- lying this coexistence is currently poorly understood. The existing literature in this field, however, is rapidly expanding, and a large body of scientific evidence cur-

554 M.C. Polidori et al. / Dementia, depression and parkinsonism: A frequent association in the elderly

rently covers the topic regarding the “associated syn- dromes of dementia”. The coexistence of either de- pression or parkinsonism with dementia might only in part be explained by the likelihood that two common age-related disorders occur in the same subject, or by a potential referral bias in the elderly with multipathol- ogy. With the aging of the population, in fact, the num- ber of subjects reaching a very advanced age is dra- matically increasing, and with this increase it is also possible to notice the growing frequency of neuropsy- chiatric comorbidities in very old subjects. This is a problem of great clinical and socio-economical inter- est, because, when present in the same subject, de- pression, parkinsonism-related motor impairment and cognitive impairment may act additively or synergisti- cally in deteriorating the functional outcome of the pa- tient. Therefore, early diagnosis and treatment of these pathologies are urgently needed.

Rather than overlapping with the existing, available data on the problems related to the diagnosis and treat- ment of depression in demented or Parkinson patients, or else of extrapyramidalism in depressed or cogni- tively impaired patients, our work will focus on pecu- liar aspects of the coexistence of depression and ex- trapyramidalism in cognitively impaired and demented patients.

2. Depression and parkinsonism in cognitive impairment and dementia

The first problem that has to be approached with great caution when dealing with cognitively impaired patients, is the detection of depressive symptoms, i.e. the differential diagnosis between depression and pri- mary dementia [46]. With respect to this, it is impor- tant to underline not only that up to half of patients with early AD have been observed to complain for de- pressive symptoms, but also that roughly half of them might fulfill criteria for major depression [13]. Sev- eral neurologic diseases have been shown to present with psychiatric symptoms [48]. Depression, whose prevalence increases with advancing age, is however too often undetected in the elderly, mainly because de- pressive symptoms might be considered as a normal aspect of aging both by the practitioner or by the fam- ily [26]. Other reasons for the underestimation of de- pressive symptoms in the elderly is that diagnostic cri- teria may be different in late life, and that it might be more difficult to retrieve older subjects in which the rate of death (survival bias), disability and institution-

alization is higher than in the adult population. It is indeed likely that, in older depressed subjects, the main or only symptom showed is represented by memory complaints or loss of orientation, so that a dementing disorder may be erroneously diagnosed. This condi- tion, initially called “pseudodementia” [25], has been studied for many years, and even a scale to distinguish between primary dementia – organic and irreversible –, from depressive dementia – treatable and reversible –, has been proposed [55].

The transition between the idea of a depressive syn- drome imitating a dementing disorder and the persua- sion that depression is often a risk factor for AD, has been to date completed [43]. Already at the beginning of the XX century, Kraepelin and colleagues hypoth- esized that depression might constitute a prodrome of AD in aged subjects [27]. The initial observation that almost all patients diagnosed has having pseudodemen- tia during the first neuropsychological evaluation had developed dementia at follow-up [28], got confirma- tion in several subsequent studies showing an associ- ation between history of depression, depressed mood, old age depression or major depression and later oc- currence of AD [17,18,23]. A recent meta-analysis has indeed shown that depression has been associated to an increased risk of developing dementia both in case-control and prospective studies [23]. Although these studies are not directly comparable, being sub- stantially different in methodological approach, they provide relevant information regarding the role of de- pression in the development of dementia. Buntinx and colleagues [6] found more than two-fold increase in the risk of developing dementia in a community of more than 19,000 depressed subjects followed up to ten years. In another study, depressed mood was also found to double the risk of dementia occurrence within up to five years [14]. A diagnosis of major depres- sion constituted an increased risk by 1.5 times in 267 patients followed at three years [39], whereas, in the whole Danish population, patients with a discharge summary from a psychiatric hospital containing a diag- nosis for affective disorder showed a highly increased risk (RR = 13.7) of developing dementia in the next two decades [24]. Only Chen et al. [7], when looking expressly for AD as the outcome diagnosis, found an increased risk (RR = 1.28) of developing this disease within four years in patients with depressive symptoms.

During the course of a dementing disorder, mainly at its beginning, depression has been also shown to occur, manifesting with tendency to cry, sadness, and vegeta- tive symptoms [40], possibly meaning a reaction to per-

M.C. Polidori et al. / Dementia, depression and parkinsonism: A frequent association in the elderly 555

ceived cognitive decline [23]. In a sample of 1366 rural community-dwellers evaluated for their cognitive and affective status every two years up to eight years, a sig- nificant risk of developing depressive symptoms after dementia occurrence (15.4%; OR 6.5, CI 2.2–19.1) or AD (17.6%; OR 5.2, CI 1.8–15.2) was also found [7]. The authors concluded that depression represented in this case an early manifestation, rather than a predictor, of dementia [7].

Pathophysiological mechanisms of the association between depression and dementia have been searched, and it has been proposed that AD could cause depres- sion through loss of noradrenergic neurons, or through vascular lesions and subcortical cerebrovascular dis- ease [23]. Late-onset depression is strongly associ- ated with vascular subcortical lesions [49], and older depressive patients with silent cerebrovascular disease often suffer from stroke later in life [29]. It has been also suggested that serotoninergic dysfunction might be partially responsible for the behavioral disturbances observed in AD [23]. Other studies attempting to un- derstand whether depression treatments are a risk factor for dementia, whether dementia and depression share common risk factors, or whether depression may lower the threshold for manifesting dementia, have not led to consistent results [23]. The “glucocorticoid cascade” hypothesis formulated by Sapolsky [47], postulating that depression-related prolonged glucocorticoid secre- tion might have a deleterious effect on the hippocam- pus – an area rich of glucocorticoid receptors – contin- ues to rise scientific interest, but it has not been proven yet. It has also been proposed that, while dysthymia may constitute an emotional reaction to the awareness of the progression of cognitive decline, major depres- sion may be related to biological factors [37].

Independent of the pathophysiological mechanism, or of the temporal occurrence of depressive symptoms during the course of dementia, the frequent coexistence of these two diseases causes many problems in the management of aged subjects. Depressive symptoms have been shown to exhibit a prevalence percentage of 30–40% in AD [54]. On the other hand, deficits on neuropsychological tests are detected with a high fre- quency in depressed patients [9]. When Migliorelli and colleagues studied a consecutive series of 103 patients with probable AD, they found that 51% of the patients had depression [37]. This aspect is important to be known because depression is able to further reduce the already impaired functional independence [41,44] and cognitive performance [30,41] of demented patients, and also because it can negatively affect the caregiver’s quality of life [33].

Another neurologic disorder frequently associated with depression is Parkinson’s disease (PD), in that has been reported with a prevalence of 30–40% [50] – sim- ilar to the average reported prevalence of depression in AD. Similar to the depressive syndrome of dementia, also parkinsonian depression has been also shown to precede the onset of motor symptoms in up to 30% of the cases [42]. On the other hand, dementia might be present in one fourth of PD patients [4], and extrapyra- midal signs – either isolated or as part of a parkinsonian syndrome – have been shown to be absent only in 8% of subjects with AD [38], and to be often detectable in depressed patients without dementia [45]. In a longi- tudinal study, it has been shown that patients with PD have a doubled risk of developing dementia than con- trols, and that predictive features of incident demen- tia in PD are represented by an extrapyramidal score greater than 25 – as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) –, and by a Hamilton Depression Rating Scale Score greater than 10 [32], despite this latter finding has not been confirmed in another study [22]. Finally, extrapyramidal signs have been reported in patients with primary depression, and have been shown to be susceptible of improvement with antidepressant therapy [45].

It has been reported that depressed patients with AD exhibit significantly more akinesia rates than AD pa- tients without depression [2]. When Merello and col- leagues [36] assessed a consecutive series of 78 AD patients, 18 of them (23%) met criteria for parkin- sonism according to the UPDRS, and 44 (56%) pre- sented isolated extrapyramidal signs. Only 16 (21%) showed no extrapyramidal signs. Interestingly, the authors found that patients with the association AD- parkinsonism showed a significantly higher frequency of major depression and significantly higher Hamilton depression scores than patients with isolated or no ex- trapyramidal signs. Furthermore, patients with AD- parkinsonism had significantly more severe deficits on neuropsychological frontal lobe-related tasks than AD patients without extrapyramidal signs. Finally, none of the patients with AD-parkinsonism who underwent the apomorphine test showed a positive motor response, and the authors suggested that parkinsonism in AD may not result from a nigrostriatal dysfunction.

The difficulty of studying elderly patients with parkinsonism, dementia and depression is shown by the relative lack of published literature on this topic. Stud- ies have been conducted, however, showing that while parkinsonian dementia parallels the length of duration of the disease but not the severity of motor disability,

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parkinsonian depression parallels both the length of du- ration of the disease and the severity of motor disabil- ity [8], and that while dementia in PD is related to older age of the subjects and later onset of the disease, de- pression in PD is related with the presence of dementia and with early onset of the disease [19]. Troster and colleagues have compared qualitative and quantitative aspects of neuropsychological performance in patients with PD having or not depression, and found that the latter exacerbates memory and language impairments related to PD, independently from demographic and disease variables, depression influencing the quantity rather than the quality of cognitive impairment associ- ated with PD [53].

The pathophysiological mechanisms associating de- mentia, depression and parkinsonism are poorly under- stood. Currently, available data suggest that the occur- rence of AD stage III brain lesions (presence of neu- rofibrillary changes in cortical and subcortical compo- nents of the limbic system) represent the most com- mon cause of intellectual decline in PD [5]. Further- more, the dopaminergic ventral tegmental area in PD patients who have depression and cognitive impairment has been shown to be largely damaged [52], a signifi- cantly lower metabolic activity in the head of the cau- date nucleus and in the orbital-inferior frontal cortex in depressed PD patients has been observed [34], and lower levels of serotonin metabolites in depressed and demented patients have been found as compared to con- trols [35]. Despite the origin of cognitive impairment in PD patients has been often defined as subcortical [32], roughly 90% of demented PD patients have cortical changes, and therefore this type of dementia should be considered of cortical type [26].

Zweig and colleagues [57] reported a significant neu- ronal loss in the noradrenergic and serotoninergic paths in depressed patients with AD as compared to non- depressed AD patients. In another study, a significant neuronal loss in the substantia nigra of depressed com- pared to non-depressed AD patients was reported [56]. Finally, Forstl et al. [16] showed a significant asso- ciation between loss of noradrenergic and cholinergic neurons and depression scores in AD, and it has been suggested that the association found in AD between depression and extrapyramidal signs might be related to a significant depletion of biogenic amines [36]. Ad- ditional to this hypothesis, it has also been proposed shared susceptibility genes might underlie the aggrega- tion of depression, dementia and PD [15].

Once again, despite the substantial lack of knowl- edge regarding the pathophysiological mechanisms un-

derlying the association depression/ dementia/ parkin- sonism in aged subjects, it is fundamental to take into consideration the fact that these comorbidities further impair patients’ disabilities, have a dramatic negative impact on the family and the caregiver [10] and con- stitute a main reason for nursing home placement [1]. Therefore, early detection and treatment are strongly recommended.

3. Our experience

We retrospectively studied a consecutive series of patients discharged in 1999 from the Department of Geriatrics of the University Hospital of Perugia, Italy, with the diagnosis of cognitive impairment or dementia associated with depression and parkinsonism. Exclu- sion criteria were represented by other neurologic or psychiatric disorders and major organ failure. Patients were enrolled in the study according to either cognitive impairment occurred three to six years before depres- sion and extrapyramidalism (group A); depression oc- curred three to six years before cognitive impairment and extrapyramidalism (group B); and extrapyramidal- ism occurred three to six years before depression and cognitive impairment (group C). Similar criteria were applied for the study of a consecutive series of patients institutionalized in two nursing homes in Umbria, Italy (Casa di Ospitalitá per Anziani “Fontenuovo”, Perugia, and Casa di Riposo “Creusa Brizi Bittoni”, Cittá della Pieve). Institutionalized patients were also divided in groups A, B and C according to the temporal onset of cognitive impairment first (group A), depression first (group B) or extrapyramidalism first (group C). Ten percent of hospitalized patients in 1999 and 50 percent of institutionalized patients fulfilled inclusion criteria.

Statistical analysis was performed with the program Statview 4.5 (Abacus Concept, 1996). All data are presented as mean ± S.D. Mann-Whitney U test was used for comparisons between groups. Chi-square was used for frequency analysis. Significance was accepted if the null hypothesis was rejected at the p < 0.05 level.

Demographic and clinical characteristics of the pa- tients in groups A, B and C are shown in Tables 1–3, respectively. Scores of Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Activi- ties of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were collected as measures of cognitive status, severity of depressive symptoms, and functional independence. Additionally, the Geriatric Functional Impairment (GEFI) scale [11] scores were

M.C. Polidori et al. / Dementia, depression and parkinsonism: A frequent association in the elderly 557

Table 1 Demographic and clinical characteristics of hospitalized and institutionalized patients in which cognitive impairment was diagnosed three to six years before the occurrence of depression and parkinsonism (A)

Hospitalized Institutionalized p-values Patients (n = 14) Patients (n = 73)

Age (years) 76.8 ± 6.7 84.2 ± 8.3 0.001 Gender (M/F) 6 / 8 19 / 54 Diabetes [n (%)] 4 (28%) 8 (11%) n.s. Hypertension [n (%)] 5 (36%) 37 (51%) n.s. Stroke [n (%)] 6 (43%) 22 (30%) n.s. Education (years) 6.5 ± 3.9 4.1 ± 3.7 0.02

Table 2 Demographic and clinical characteristics of hospitalized and institutionalized patients in which depression was diagnosed three to six years before the occurrence of cognitive impairment and parkinsonism (B)

Hospitalized Institutionalized p-values Patients (n = 23) Patients (n = 21)

Age (years) 78.5 ± 6.1 81.0 ± 8.4 n.s. Gender (M/F) 4 / 19 7 / 14 Diabetes [n (%)] 6 (26%) 7 (33%) n.s. Hypertension [n (%)] 6 (26%) 11 (52%) n.s. Stroke [n (%)] 3 (13%) 4 (19%) n.s. Education (years) 6.1 ± 5.9 4.5 ± 3.7 n.s.

Table 3 Demographic and clinical characteristics of hospitalized and institutional- ized patients in which parkinsonism was diagnosed three to six before the occurrence of depression and cognitive impairment (C)

Hospitalized Institutionalized p-values Patients (n = 15) Patients (n = 13)

Age (years) 75.8 ± 7.4 81.2 ± 6.3 0.025 Gender (M/F) 4 / 11 10 / 3 Diabetes [n (%)] 4 (27%) 1 (7%) n.s. Hypertension [n (%)] 5 (33%) 6 (46%) n.s. Stroke [n (%)] – 3 (23%) n.s. Education (years) 7.3 ± 5.9 5.2 ± 4.0 n.s.

used to quantify the overall loss of autonomy of pa- tients studied. The GEFI scale is subdivided in two sections. Section A comprises ten medico-biological factors on each one of which a score from 0 up to 100 can be given. Medico-biological factors include abil- ity in walking (five grades of increasing dependence, from completely independent, score 0, to constricted in bed, score 100), mental status (four grades of increas- ing severity, from full ability to talk and understand, score 0, to aggressive behavior, score 100), temporo- spatial orientation (four grades of decreasing orienta- tion, from fully oriented, score 0, to stably disoriented, score 100), sensorial functions (six grades of increas- ing sensorial deficits, from no deficit, score 0, to severe hearing and sight loss, score 100), sphyncterial control (five grades of decreasing control from complete con-

trol, score 0, to double incontinence, score 100), pres- ence of decubits (four grades of increasing sever- ity, from no decubits, score 0, to stage IV decubits, score 100), nutrition (three grades of increasing depen- dence in feeding, from independent, score 0, to fully dependent, score 50), self-care (three grades of increas- ing dependence from independent, score 0, to fully de- pendent, score 50), sleeping habit (four grades of in- creasing severity of sleep disturbances, from regular sleep, score 0, to rhythm inversion, score 50), and gen- eral health status (four grades of increasing severity of the general conditions from good, score 0, to need of daily treatment, score 75). A subtotal score is given to section A. Section B includes five socio-environmental factors on each one of which a score from 0 up to 50 can be given. Socio-environmental factors include need of nurse assistance (five grades of increasing need, from no need, score 0, to daily need, score 50), liv-

558 M.C. Polidori et al. / Dementia, depression and parkinsonism: A frequent association in the elderly

M M

S E

A (n.14) B (n.23) C (n.13)B (n.21)A (n.73)C (n.15)

Hospitalized Institutionalized

Fig. 1. MMSE scores in hospitalized (n = 52) and in institutionalized (n = 107) patients in which cognitive impairment was diagnosed three to six years before the occurrence of depression and parkinsonism (A), in which depression was diagnosed three to six years before the occurrence of cognitive impairment and parkinsonism (B), and in which parkinsonism was diagnosed three to six years before the occurrence of cognitive impairment and depression (C). ∗p = 0.04 A vs. A.

G D

A B C A B C Hospitalized Institutionalized

* §

** ***

Fig. 2. GDS scores in hospitalized (n = 52) and in institutionalized (n = 107) patients in which cognitive impairment was diagnosed three to six years before the occurrence of depression and parkinsonism (A), in which depression was diagnosed three to six years before the occurrence of cognitive impairment and parkinsonism (B), and in which parkinsonism was diagnosed three to six years before the occurrence of cognitive impairment and depression (C). ∗p = 0.001 A vs. A; ∗ ∗ p = 0.026 B vs. B; ∗ ∗ ∗p = 0.022 C vs. C; ßp = 0.007 B vs. A in hospitalized patients.

ing arrangement (three grades of increasing discomfort from idoneous house, score 0, to architectural barriers, score 25), family conditions (four grades of decreasing support by the family, from fully supportive, score 0, to full absence of family’s and friends’ support, score 50), financial conditions (five grades of increasing finan- cial need, from no need, score 0, to extreme poverty, score 25), and social exposure (five grades of decreas- ing exposure, from active and independent contacts, score 0, to isolation, score 50). A subtotal score is given to section B also, and the global score is constituted by the sub of sections A and B subtotals. A total score < 100 is considered independence, 100 to 200 partial independence, and > 200 dependence. A total score of 1000 means complete lost of functional autonomy.

As shown in Figs 1–5, elderly institutionalized pa- tients with cognitive, behavioral, and motor comorbidi- ties show a poorer performance on MMSE (Fig. 1), are significantly more depressed (Fig. 2) and significantly less functionally independent (Fig. 3–5) in comparison to elderly hospitalized patients belonging to the same disease categories, independent of which disease (cog- nitive impairment, depression or extrapyramidalism) is diagnosed first. Although one could argue that this dif- ference might be partly due to age variation between institutionalized and hospitalized patients (Tables 1 and 3), age alone does not explain these findings: group B institutionalized patients, for instance, are significantly more depressed and significantly less functionally in- dependent as compared to hospitalized patients of the

M.C. Polidori et al. / Dementia, depression and parkinsonism: A frequent association in the elderly 559

A D

A B C A B C Hospitalized Institutionalized

* **

§ §§

Fig. 3. ADL scores in hospitalized (n = 52) and in institutionalized (n = 107) patients in which cognitive impairment was diagnosed three to six years before the occurrence of depression and parkinsonism (A), in which depression was diagnosed three to six years before the occurrence of cognitive impairment and parkinsonism (B), and in which parkinsonism was diagnosed three to six years before the occurrence of cognitive impairment and depression (C). ∗p = 0.0001 A vs. A; ∗ ∗ p = 0.006 C vs. C; ßp < 0.05 C vs. B in institutionalized patients; ßßp < 0.0001 A vs. B in institutionalized patients.

IA D

A B C

Hospitalized

A B C

Institutionalized

* ** ***

Fig. 4. IADL scores in hospitalized (n = 52) and in institutionalized (n = 107) patients in which cognitive impairment was diagnosed three to six years before the occurrence of depression and parkinsonism (A), in which depression was diagnosed three to six years before the occurrence of cognitive impairment and parkinsonism (B), and in which parkinsonism was diagnosed three to six years before the occurrence of cognitive impairment and depression (C). ∗p = 0.002 A vs. A; ∗ ∗ p = 0.023 B vs. B; ∗ ∗ ∗p = 0.01 C vs. C; ßp = 0.01 A vs. B in institutionalized patients.

same group, despite not significantly older than the lat- ter (Figs. 2–5). Another interesting finding is that both hospitalized and institutionalized patients of groups A, B and C did not show significant differences of per- formance on MMSE (Fig. 1), despite in group A pa- tients cognitive impairment was diagnosed at least three years before than in group B and C patients. A simi- lar observation could be transposed to GDS scores, not significantly different between groups in institutional- ized patients (Fig. 2). Finally, and in agreement with what expected, Fig. 5 shows that while cognitively im- paired, depressed, and parkinsonian hospitalized pa- tients maintain a satisfactory degree of independence expressed both in term of medico-biological, assisten-

tial and socio-environmental autonomy – GEFI scores being mostly below 200 –, institutionalized patients showed a significantly higher degree of dependence, with mean GEFI scores above 400.

4. Summary

Cognitive impairment, depression and parkinsonism constitute a frequent association in the elderly, either community-dwelling or hospitalized, much more of- ten in the institutionalized elderly. These three comor- bidities are synergistic in deteriorating mental, behav- ioral, and motor performance of subjects affected, but

560 M.C. Polidori et al. / Dementia, depression and parkinsonism: A frequent association in the elderly

100

200

300

400

500

600

700

800

900

G E

F I

A B C A B C

Hospitalized Institutionalized

* * *

Fig. 5. GEFI scores in hospitalized (n = 52) and in institutionalized (n = 107) patients in which cognitive impairment was diagnosed three to six years before the occurrence of depression and parkinsonism (A), in which depression was diagnosed three to six years before the occurrence of cognitive impairment and parkinsonism (B), and in which parkinsonism was diagnosed three to six years before the occurrence of cognitive impairment and depression (C). ∗p < 0.0001 A vs. A; ∗p < 0.0001 B vs. B; ∗p < 0.0001 C vs. C; ßp = 0.01 A vs. B in institutionalized patients.

most importantly influence negatively their indepen- dence and quality of life as well as the quality of life of the family and caregiver. As a consequence, the coexistence of cognitive impairment, depression and parkinsonism is a major cause of institutionalization in older subjects. We observed that one half of in- stitutionalized subjects in two nursing homes of Cen- tral Italy suffer from an associated syndrome demen- tia/parkinsonism/depression, that these subjects are sig- nificantly more dependent than subjects hospitalized for the same reasons, and that their grade of depres- sion or cognitive impairment is not associated with the temporal occurrence of depressive, cognitive, or parkinsonian symptoms (i.e. it is independent of which disease is diagnosed first). Early diagnosis and treat- ment of these pathologies are highly recommended; despite this urgency, depressed mood, memory impair- ment and motor difficulties are often underestimated in the elderly, being considered as “normal” aspects of the aging process. Although many studies have been conducted to improve the understanding of the patho- physiological mechanisms underlying the association of cognitive impairment/dementia with depression and parkinsonism in advanced age, these mechanisms are still poorly understood. The current difficulties in pharmacologically managing the association cogni- tive impairment/dementia-depression-parkinsonism in older patients could take substantial advantage of the identification of a common pathophysiological path- way.

Acknowledgements

M.C. Polidori is an EU Marie Curie Fellow for the Programme “Quality of Life and Management of Liv- ing Resources”, project entitled “Nutritional health- sustaining factors and determinants of healthy aging: oxidative stress-related biomarkers of successful aging and age-related diseases”.

The authors would like to thank G. Balducci, P. Abbatiello, C. Passeri, C. Rizzotto, C. Furiani and F. Germini from the Casa di Ospitalitá per Anziani “Fontenuovo”, Fondazione O.N.L.U.S., Perugia, Italy; S. Picchio, M. Fatichenti, N. Popa, S. Simoncini and A. Sorbino from the Casa di Riposo “Creusa Brizi Bit- toni”, Cittá della Pieve, Perugia, Italy; and the Nurse Staff of the Geriatric In-Patient Unit of the University Hospital of Perugia, Italy, for their kind collaboration.

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