Physical Exercise for Late-Life Major Depression.

(Reprinted with permission from Br J Psychiatry 2005; 207: 235-242).

Physical exercise for late-life major depression.

BACKGROUND: Interventions including physical exercise may help improve the outcomes of late-life major depression, but few studies are available. AIMS: To investigate whether augmenting sertraline therapy with physical exercise leads to better outcomes of late-life major depression. METHOD: Primary care patients (465 years) with major depression were randomised to 24 weeks of higher-intensity, progressive aerobic exercise plus sertraline (S+PAE), lower-intensity, non-progressive exercise plus sertraline (S+NPE) and sertraline alone. The primary outcome was remission (a score of ≤10 on the Hamilton Rating Scale for Depression). RESULTS: A total of 121 patients were included. At study end, 45% of participants in the sertraline group, 73% of those in the S+NPE group and 81% of those in the S+PAE group achieved remission (P = 0.001). A shorter time to remission was observed in the S+PAE group than in the sertraline-only group. CONCLUSIONS: Physical exercise may be a safe and effective augmentation to antidepressant therapy in late-life major depression.

Insulin-like growth factor-1 (IGF-1): relation with cognitive functioning and neuroimaging marker of brain damage in a sample of hypertensive elderly subjects.

IGF-1 decline has been related to age-dependent cognitive impairment and dementia. No study examined IGF-1 levels in subjects with a risk factor for brain damage such as hypertension. We investigated the relationship between IGF-1, cognitive functioning and neuroimaging in a sample of 75 hypertensive elderly subjects aged > 65. Cognitive performance were tested by mini mental state examination (MMSE), Cambridge cognitive examination (CAMDEX-R), and the frontal assessment battery (FAB). Among other indices, free IGF-1 in serum was assayed. The radial width of the temporal horn (rWTH) evaluates medial cerebral temporal lobe atrophy. Significant correlations between IGF-1 levels and both total and sub-domain scores of cognition were found. IGF-1 level was significantly lower in cognitively declined group. The lowest IGF-1 -percentile subgroup was significantly cognitively impaired. A statistically non-significant, but lower IGF-1 level was found in the sub-sample with pathologically wider rWTH. Levels of IGF-1 below 79.4 microg/l are associated with cognitive decline, whereas a level above 118 microg/l seems to be a marker of normal cognitive performance. A decreasing of IGF-1 related to a widening of the rWTH suggests an involvement of this hormone in hippocampus atrophy.

Relations between a novel, reliable, and rapid index of arterial compliance (PP-HDI) and well-established inidices of arterial blood pressure (ABP) in a sample of hypertensive elderly subjects.

Hypertension is a risk factor for a long-lasting arterial wall-remodelling leading to stiffness. The rapid method measuring the pulse pressure (PP) by means of the tool of Hypertension Diagnostic Instruments (HDI) called PP-HDI, overcomes some of the problems arising with more-time consuming methods, like ambulatory blood pressure monitoring (ABPM), and give information about the elasticity of the arterial walls. We studied the relationship between the PP-HDI, the large artery compliance (LA-C) and small artery compliance (SA-C) and few well-established indices of arterial blood pressure (ABP) in a sample of 75 hypertensive subjects, aged 65 years and over. Significant correlations between LA-C and heart rate (HR), PP-ABPM and PP-HDI were found. SA-C relates with HR and systolic blood pressure (SBP) measured in lying and standing positions. Applying a stepwise regression analysis, we found that LA-C variance stems from PP-HDI and HR, while SA-C variance stems from SBP in lying position. Receiver operator characteristic (ROC) curves for thresholds of PP showed that PP-HDI reached levels of sensitivity/specificity similar to PP-ABPM. In conclusion, surveillance of ABP through hemo-dynamic indices, in particular of SBP, is essential, nevertheless the advantage of this control is not known in an elderly population where the organ damage is already evident. PP needs necessarily an instrumental measurement. The PP-HDI result is similar in reliability with respect to PPABPM, but is more rapid and well applicable in an elderly population.

A scale evaluating the emotivity and well-being of elderly (Italian acronym: SVEBA): analysis of psychometric characteristics.

The psychopathology in the aged is an increasing burden for the last decades of the life and a large source of expenditure. An early recognition and treatment could lead to reduce personal distress and improve prognosis. For the use in the general practitioner (GP) office and ward settings most of the short check-lists available are focused on depression symptoms. For this reason a 15 items check-list, oriented to cover a wider array of symptoms, has been designed for the Italian population in the '90 (called SVEBA abbreviated from its Italian name). This work intended to investigate the presence of symptomatological clusters in order to detect different profiles of symptoms in populations with different comorbidities, in 214 home-dwelling elderly, with a mean age 80.2 years, referred to the geriatric memory clinic. We used the Keiser-Meyer-Olkin and Bartlett tests to check for applicability of factorial analysis, then a principal axis factoring extraction method was applied. The analysis identified the following factors: the first, collected items related to lack of motivation and initiative The second is related to the perceived "locus of control". The third, collected items related to sleep disturbance. The fourth, included items related to somatic complaints and anxiety. In the structure of SVEBA index is possible to identify three main symptom profiles related to motivation, anxiety and somatic symptoms and sleep disturbances.

Behavioral and psychological symptoms of dementia (BPSD) in elderly demented subjects: is the long lasting use of atypical antipsychotic drugs useful and safe?

The use of atypical antipsychotics (AA) is suggested in the treatment of BPSD, although controversial data are available on their safety and efficacy. The aim of this study was to assess the efficacy and safety of AA and whether this therapy could modify cognitive and functional domains in parallel with BPSD modifications. Out of 1,100 patients followed by the psychogeriatric ambulatory of our hospital, 69 patients (6.2%) were in therapy with AA and only 32 of them fulfilled the inclusion criteria of this study. Namely, the availability was required of a complete geriatric assessment, including the evaluation of cognitive (mini mental state examination=MMSE), emotional (the Italian "scala di valutazione del benessere emotivo nell'anziano"=SVEBA), functional (basic and instrumental activities of daily living=ADL and IADL), as well as behavioral (neuropsychological inventory=NPI) status, at the beginning (T(0)) and after a 6 month therapy (T(1)). The AA prescribed were risperidone (42.8%), olanzapine (31.3%), quetiapine (25.9%). The mean age was 80.1 years; 34.4% male; 65.6% female. Educational level was elementary in 90.6% of cases. Only 21.9% were institutionalized. 15.6% had 1 cardiovascular risk factor (CVRF), 50% more than 1, and the remaining with no CVRF. More than the half of them were diagnosed with degenerative dementia (D) (40.6% Alzheimer D=AD; 15.6% fronto-temporal dementia (FTD); 34.4% with vascular dementia (VD) (9.4%) or combined D (25%); 3,1 % with mild cognitive impairment (MCI), classified as F06.7 by the ICD-10 (International Classification of Diseases) and 6.2% with psychiatric disturbances. The most common BPSD were hallucinations, delusions, agitation, verbal and physical aggression. A paired t-test was applied to analyze data. There was a significant improvement with all 3 AA on NPI (mean NPI T(0)=27.50 vs. T(1)=12.13; t=7.49). An improvement was also observed on SVEBA (t=1.97), close to significance. Most people did not have any adverse effects; 5 patients (15.6%) had extrapyramidal symptoms and 1 (3.1%) showed ginecomasty, clinically so relevant to cause the interruption of the treatment. The profile of safety and efficacy described on the whole sample was confirmed when it was subdivided according to kind of drug, illness severity and presence/absence of CVRF. In a large sample of the "real" subjects attending a geriatric service for dementia, the accurate selection of patients treatable with AA leads to identification of a population with a negligible rate of adverse effects in presence of a high rate of efficacy with respect not only to BPSD but also to cognitive and functional domains.

Relation of neurocardiovascular instability to cognitive, emotional and functional domains.

There is bulk of evidence suggesting that blood pressure dysregulation, as low blood pressure (LBP) or hypotension, orthostatic hypotension (OH) and high blood pressure (HPB) or hypertension are associated with alterations in cognitive and emotional domains. Some studies suggest that LBP, neurocardiovascular instability, like the OH, and atherosclerosis resulting from long standing HBP, reduces cerebral blood flow, increasing the risk of cognitive impairment, morbidity and mortality. This study aims to evaluate whether patients with cognitive impairment and cardiovascular disease would show any differences in some anamnestic indicators and/or psychometric measures of cognitive performance and affective symptoms. We recruited 36 patients over 65 years of age admitted to both psycho- and cardio-geriatric ambulatories of our hospital during the last year. The population (mean age of 80.5 years, 72.2% females, 27.8% males) was divided in 2 groups, with OH (25%), and without OH (75%). The first group was subdivided in subgroups: patients with HBP, normal BP and LBP, respectively. Cognitive and depressive domains were assessed with the mini mental state examination (MMSE) and the Italian "scala di valutazione del benessere emotivo nell' anziano" (SVEBA). Information about the present status, comorbidities (cumulative illness rating scale=CIRS), functional ability (activities of daily living=ADL, instrumental ADL=IADL) and drugs were collected during clinical examination. BP was measured 4 times, at the beginning of examination, then with the patient in clinostatic and orthostatic position (1st and 3rd minute). Data were analyzed by MANCOVA, considering age and gender as covariates, MMSE, SVEBA, CIRS, ADL, IADL and drugs as dependent variables, and presence/absence of OH as factor. Covariates were not significant sources of variance, as well as overall factor. Due to the heuristic aim of the study, we considered of interest the results of subsequent ANOVAs showing significant differences in SVEBA and ADL with respect to the factor. These data give us the basis to develop a longitudinal study to confirm the detrimental effect of OH on a wide range of health domains.

Multidimensional evaluation of home-dwelling elderly: the impact of medical and social factors on health status indices.

Since 1980 the WHO has proposed at least tree indices to characterize health status (impairment, disease, disability). Their relationships have been examined in some chronic diseases, but little is known about elderly at risk of frailty. We studied the influence of gender, age and living conditions on these indices and on their relationships. A sample of 100 home-dwelling elderly subjects underwent a multidimensional assessment at home to collect biological, symptomatic and functional measures. The sample consists of 48 males and 47 females, their mean age was 80.2 years, the mean schooling was 4.7 years. Living at home alone 14%, with spouse 60%, other 26%. Applying a MANOVA that considered the above mentioned items as factors and the biological, symptomatic and functional measures as dependent variables, no significant difference was found in biological measures, whereas the interaction of (i) gender and living conditions, (ii) gender and age classes showed differences in affective symptoms. Moreover, gender alone resulted a significant source of differences in instrumental activities of daily living (IADL). To assay the impact of biological, symptomatic scores on disability, a backward linear regression was applied. The principal index of postural control, Tinetti scale score, alone explained 50% of variance in activities of daily living (ADL), this index together with the measures, respectively, of cognitive functioning (Camcog score) and behavioral profile neuro-psychological inventory (NPI) score resulted to be the main sources of the IADL variance. These preliminary data allow us to identify both medical and social factors able to enhance the risk of frailty; is worth wile to stress that prevention programs could be targeted on possible modification of these factors.

Evaluation of the slopes of cognitive impairment and disability in Alzheimer's disease (AD) patients treated with acetylcholinesterase inhibitors (AChEl).

AD is characterized by a widespread cognitive impairment and deficit in functional competency to perform activities of daily living (ADL). The longitudinal reliability of cognitive and functional performance indices and the strength of relationship between patients cognitive impairment and their functional competence are still open issues. The aim of this study has been to evaluate, in a selected sample of patients with AD treated with AChEl, the slopes of cognitive impairment and disability. Among 249 AD patients, according to DSM-IV criteria, with presence/absence of associated vascular lesions (AD+VD), eligible for AChEl treatment, we selected subjects with mild to moderate cognitive impairment, without high comorbidity and severe psychiatric disease, with caregiver who resided with, or had frequent contact with the patient. Patients that changed treatment shifting from one AChEl to another, that didn't tolerate inhibitors (drop-out), and that presented behavioral and psychological symptoms of dementia (BPSD) requiring neuroleptic treatment during the study period were excluded from the final analysis. A sample of 99 subjects (30 males, 69 females; mean age of 79.4+/-5.0 years), completing a 15 months follow-up was considered. Cognitive performance remained stable after 15 months of treatment, but disability increased. No difference was found due to the AChEl compound used. The same hold true for the subgroups with presence/absence of a vascular components, whereas subgroup with mild cognitive performance showed a cognitive decline, parallel to the functional one. Our data underline the efficacy of AChEl in the treatment of AD with presence/absence of vascular component. Nevertheless, the judgement on the level of efficacy of AChEl could be biased by the level of reliability of the indices considered.