Geriatric Depression and Cognitive Impairment: A Follow up Study

Introduction: Depression in older adults has become a major problem for public health. A high percentage of this population is under-diagnosed in primary care. The objectives of this work were firstly, to investigate the causes, risk factors, cognitive profile, functional status and quality of life of patients with geriatric depression, and secondly, to make a follow up of these patients. Materials and methods: Patients who consulted for memory problems associated with depression were recruited during the years 2005-2007. A semi-structured neuropsychiatric interview, an extensive neuropsychological battery, and complementary studies were performed. Results: One hundred and one depressive patients and 25 normal controls were evaluated. There was a significant prevalence and incidence of depression in the geriatric population. Significant differences (p<0.05) were found between depressive patients and controls in dyslipidemia, heart disease, cerebrovascular disease, inadequate family support, family history of depression and inactivity (OR 6.5). A global cognitive impairment was frequently associated with depression. Depression caused an alteration in functional status. Follow up results: From the 101 patients evaluated only 61 attended to the follow up visit (61.4%). All patients were indicated antidepressant treatment. Of these, only 36 patients continue with the treatment indicated in the baseline visit. Of the patients who were in antidepressant treatment (n=36) 46.6% had an excellent to good response, and 13.3% had a response from fair to poor. The main causes of poor response were adverse effects, low-dose and treatment neglect. Of the reevaluated patients, 56.6% improved in cognition or mood. The greatest improvement was observed in depression and anxiety affective symptoms. Within the cognitive profile, memory and attention trend to improve with medical treatment. Conclusion: Depression is a prevalent disease in the elderly population. It is important to implement health policies to inform the community, prevent associated risk factors, and promote appropriate treatments and rehabilitation. This condition not only affects the patient but also their environment.


Introduction
More than 350 million people are affected by depression making it one of the most common disorders in the world. It is the biggest cause of disability, and as many as two-thirds of those who commit suicide have the condition. But although depression is common, it is often ignored [1].
Depression in older adults is a very common condition that creates a major problem for public health [2]. A high percentage of this population is under-diagnosed in primary care [3].
It has been demonstrated that depression is associated with cognitive impairment due to vascular factors [4], degenerative process [5], or emotional compromise. Moreover, it could be also related with social and psychological distress situations [6,7], or co-morbid clinical diseases (chronic diseases, cancer, neurological diseases, etc.) [8,9].
It is frequently under-diagnosed in clinical practice, mostly in those patients with late onset geriatric depression that develop subsyndromal depressive symptoms where memory and other cognitive functions are mildly impaired [10,11]. These patients minimize their symptoms thinking that it is normal to have them due to their social problems or their co-morbid diseases. These factors attempt against an effective treatment for depressive syndromes and probably these symptoms will last for months or even years without a proper treatment.
The objectives of this work were firstly, to investigate the causes, risk factors, cognitive profile, functional status and quality of life of patients with geriatric depression, and secondly, to make a follow up of these patients.

Materials and Methods
Patients who consulted for memory problems associated with depression to a memory clinic from a public (Memory Research Center, Zubizarreta Hospital) and a private Hospital (SIREN-CEMIC University Hospital) were recruited during the years 2005-2007. A semi-structured neuropsychiatric interview and an extensive neuropsychological battery with complementary studies were performed.

Inclusion criteria
Patients who present depressive symptoms due to psychiatric causes or are related to dementia (clinical dementia rating scale 1-CDR). Patients more than 55 years and less than 80 years old. Patients with Hamilton depression scale more than 9 points and Beck depression inventory more than 9 points.

Exclusion criteria
Patients with schizophrenia or schizoaffective disorder. Patients with Hamilton depression scale less than 10 points and Beck depression inventory less than 10 points. Patients less than 55 years old. History of drug or alcohol abuse. Moderate or severe dementia (CDR 2, or CDR 3).
All patients were assessed using a semi-structured neuropsychiatric interview (administered by specialized psychiatrists and neurologists). Depressive syndromes were categorized into different diagnoses according to the diagnostic and statistical manual of mental disorders (DSM IV) and international codification of diseases (ICD 10) criteria, using schedules for clinical assessment in neuropsychiatry (SCAN 2.1) [12,13].
Other psychiatric scales were performed including Hamilton depression scale and Beck depression inventory to evaluate level of depression, and Hamilton anxiety scale to determine level of anxiety [14][15][16]. Also, neuropsychiatric inventory (NPI) was administered to the patient's caregivers in order to collect more data from the patientsb ehavior [17].
Patients and normal controls were matched by age, education and overall cognitive status using the mini-mental state examination (MMSE) and the clinical dementia rating (CDR) instrument. CDR was administered as a severity rating scale [18,19].

Laboratory Analysis Were Done Neuroimaging
Computed tomography scan (CT) or magnetic resonance imaging (MRI) were done in patients with neurological symptoms.
Written informed consent was obtained from each subject after they had been given a full explanation of the study. The research was performed in accordance with the International Conference of Harmonization Good Clinical Practice guidelines, the latest revision of the 1964 Helsinki Declaration, and the Buenos Aires Government Health Authorities regulations [29].

Follow up
After recruiting and evaluating the depressive patients and normal controls at baseline, we indicated antidepressant treatment (SSRI´s type: sertraline 25-50 mg per day or escitalopram 10 mg per day). Follow-up visits were performed after at least 6 months of treatment.

Data analysis
Statistical Package SSPS 15.1 was used to analyze data. Demographic variables for both populations (patients and controls) as well as the results of neuropsychiatric and neuropsychological general global tests were expressed as means, standard deviation and medians.
Quantitative variables were compared using Student T test for different groups (independent samples) and Student T test (related samples) for the comparison of the follow up of a group. The relationship between qualitative variables was compared by the chisquared test. Predictive factors for depression were analyzed using the odds ratio (OR) with 95% confidence intervals (95% CI).

Demographic data
A hundred and one depressive patients and 25 normal controls were evaluated. There was a significant prevalence and incidence of depression in the geriatric population. See demographic data in Table  1.

Diagnosis of Depression Mood Disorder
In the study population, 36 patients with mayor depression and 34 patients with dysthymia were diagnosed. From the patients with Major Depressive Disorder, 7 had bipolar disorder. Of the patients with Depression due to Medical Conditions: 10 had Vascular Dementia, 10 Alzheimer's type Dementia and 6 Frontotemporal type Dementia; all of them were CDR 1 (mild dementia) ( Table 2).

Neurological examination
The results of the neurological examination are depicted in Table 3.

Laboratory
Media and standard deviation of the following tests were evaluated: Hematocrit, eritrosedimentation, glycemia, cholesterol, THS, B12 vitamin, folic acid. Findings showed in Table 4.  Neuroimaging results are resumed in Table 5.

Risk Factors
Significant differences (p<0.05) in dyslipidemia, heart disease, cerebrovascular disease, inadequate family support, family history of depression and passive patients were found compared to normal controls. It was demonstrated that inactivity produces a relative risk of 6.5 of developing depression (Tables 6 and 7).

Hypertension
We observed that 48 patients (47.5% of the study population) have diagnosed and treated hypertension. It was also noted that 13 patients had systolic blood pressure greater than 140 and diastolic blood pressure greater than 95; 5 of these patients were not diagnosed as hypertensive (12.8% of the study population).

Diabetes
It was found that 11.1% of patients had DBT type 2. Of these, 5.5% had glycemic control beyond the upper normal limit (greater than 110 mg/dl).

Psychiatric history
53 patients had a depressive episode before 60 years old and 48 patients had depressive episodes after that age. Total population was divided in two groups: late onset depression and early onset depression. The late onset depression patients were defined as those who had a depressive episode after they were 60 years old [30].

Family history
In the depressive group there were 52 patients with family psychiatric history, being the most frequent conditions depression and dementia. On the other hand, there were 11 individuals in the control group with family psychiatric history. When we evaluated the Depressive group there were 33 relatives with depression history and only 3 in the control group.

Activities of daily living
We used an activity of daily living scale (ADL). It was filled by the patient and a relative. The objective was to compare the information provided by both of them. Each item was value in three ways: 0: independent; 1: partial dependence; 2: total dependence. The ADL total mean informed by patients was 1.36 (S.D. 2.4) rank between 0-14; the ADL total mean informed by relatives was 2.04 (S.D. 2.64) rank 0-9 (

Follow-up results
Thirty nine patients (38.6%) were contacted but did not attend the follow-up visits, and sixty one patients were evaluated (61.4%) and followed-up. In this last group, only thirty six patients continue with the antidepressant treatment indicated at the baseline visit.
Of the patients who were in antidepressant treatment (n=36) 46.6% said they had a response from excellent to good to antidepressant treatment, and 13.3% had a response from fair to poor. Of all patients in follow-up (n=61) 41.6% received prior antidepressant treatment. From these, 28% said to have responded well to previous antidepressant treatment, and 72% had a fair to poor response. The main causes of poor response were adverse effects, low-dose and treatment neglect.
Of the reevaluated patients, 56.6% improved in any area either cognitive or mood. Improvement was described in the mood (anxiety and depression) and into cognitive functions (memory, attention, executive functions and language) ( Table 11). The greatest improvement was observed in depression and anxiety affective spheres. Within the cognitive profile, memory was the most improved function, and, secondly, attention (Tables 12 and 13).

Discussion
With the results obtained in this research we arrived to the following conclusions:

Demographic data
There was a significant predominance of female patients, 79.7% of the studied population. Prospective studies reveal more incidence of major depression among women compared to men [31,32], this could be considered as a predisposing factor for the development of the disease. From the observed population, 58.5% is married; the rest is divorced, widowed, single or separate. Widowhood, singleness and separation or divorce are risk factors for developing depression [33][34][35][36]. With regard to educational level average in our patients is about 8.73 (SD 4.4) years, where most of the patients completed primary school. Low education is a risk factor for depression [32].

Diagnosis of depression mood disorder
In this study population, they were found in decreasing order 36.3% of patients with major depression (according to DSM-IV and ICD-10), and 34.3% of patients with dysthymia (according to DSM IV and ICD-10. From the patients with Major Depressive Disorder, 7 of them had bipolar disorder. Of the patients with Depression due to Medical Conditions (n=26, 25.7%): 10 had Vascular Dementia, 10 Alzheimer's type Dementia and 6 Frontotemporal type Dementia. All of them were scored CDR 1 (mild dementia).
In the geriatric population, it could be considered that neurological diseases, such as vascular and degenerative dementia, become important in the development of depression as it has been described in previous work [37].

Risk factors
In the present study we considered medical, psychiatric and sociological risk factors.
There is an assumption of executive dysfunction in late-onset depression [30,38,39]. This hypothesis suggests that a subgroup of elderly people with depression, with fronto-striatal dysfunction caused by cerebrovascular disease or other age-related conditions, would be the main predisposing factor for depression [30].
In previous studies depression was associated with concomitant diseases [34], previous personality, altered functional status [33], alcohol abuse [40], hypothyroidism and lack of family support.
Of the evaluated risk factors (including both vascular and depression themselves) no significant differences (p <0.05) were found compared to normal controls in variables as HTA, DBT, smoking, alcohol consumption, concomitant diseases, and marital status. On the other hand, significant differences were found (p <0.05) in patients with dyslipidemia (OR 3.3, CI 1.16-9.6), heart disease (OR 4.4, CI 1.01-20.6), cerebrovascular disease (OR 8.5, CI 1.1-66.7), currently active or working (OR 6.5, CI 2. 26-18.8), inadequate family support (OR 3.2, CI 1.04-10.35), and family history of depression (OR 3.6, CI 1.01-12.9). Yaka et al. reported that the following variables were risk factors for depression: obstructive pulmonary disease, psychiatric disease, cerebrovascular disease, low income and being dependent [41]. Moreover, a meta-analysis showed that, compared with the elderly without chronic disease, those with chronic disease had higher risk for depression [42]. The lack of activity or work produces a relative risk of 6.5 of developing depression.

Cognitive functions
Depression is a mental illness that affects not only psychologically (mood disorder) but also cognitively (through cognitive impairment) [43,44]. Depression in older patients could be an expression of neuronal degeneration and initial symptom of a dementia [44]. This should be considered in any patient that begins his/her depression after he/she is 60 years old (late-onset depression).

Daily life activities
It was observed that, in general, patients had some degree of dependence (partial dependence) in activities of daily living. This certainly increases the overload (the average overload found in our sample was mild to moderate). It was noted that increase degrees of depression increases the patient's dependence.
Depression causes a reduction in the active life of 4 years [45]. Depression causes an alteration in the functional status of people, damaging both the quality of life of patients and their environment (family overload) [46].
As the degree of depression increases, the dependence of the patient and family overload also increase. All this leads to generate significant health expenditures increasing costs associated with this disease [47]. 47.7% of depressive patients included in this work were without antidepressant treatment at baseline visit. This shows the lack of information received by general population about this disease, and hence the low demand for medical care.

Follow-up
We recruited 101 depressive patients and 25 normal controls at baseline, then proceeded to see the evolution of these depressive patients who spent at least 6 months after their first visit.
We contacted all patients but only 61 of them could be reevaluated, (60.4%). Remaining patients were summoned for missing evaluations (at least cited twice). Of contacted and reassessed patients only 60% receive antidepressant treatment, despite the indication of treatment to all patients enrolled in 2005-2006. Of the patients who are in antidepressant treatment (n=36) 46.6% said they had an excellent to good response to antidepressant, and 13.3% had a response from fair to poor. Of all patients in follow-up (n=61) 41.6% received prior antidepressant treatment. They responded excellent to good to previous antidepressant treatment in 28% of cases, and fair to poor in 72%. The main cause of fair to poor response was adverse effects, low-dose and treatment neglect.
Of the reevaluated patients 56.6% improved in any area, either cognitive or mood. The greatest improvement was observed in depression and anxiety affective spheres. Within the cognitive profile, memory was the most improved function, and, secondly, attention.
Statistically analysis (Student test for related samples) of results obtained in the different neuropsychiatric and neuropsychological scales, informed significant differences (p<0.05) in neuropsychiatric scales between the initial assessment and reassessment (Hamilton anxiety scale, Hamilton depression and Beck depression).
As it had been reported in other studies, the present work shows that there is a predominance of women in the depression patients group [31,48] and a high percentage of depressed patients without any social support [41,49].
An important prevalence and incidence of depression in the elderly population was observed. Nevertheless, a high percentage of patients do not receive or never received antidepressant treatment as it was reported previously [50]. However, after receiving treatment, our patients underwent an improvement in their affective state (anxiety, depression).

Limitations
The following study is an epidemiological and case-control research study with follow-up. It is not a randomized controlled trial. The data obtained is descriptive and shows a trend that cannot be taken in consideration as an specific response to a singular antidepressant treatment. Moreover, the antidepressant treatment indicated had two different medications [sertraline (25-50 mg/day) and escitalopram (10 mg/day)]. No reference to other medications is described in this research, as it is out of the aims of the study. Also, patients at follow-up were not divided in groups, all depressive patients were in a single group; this can lead to certain bias in the results as patients with dementia will not beneficiate as well as major depressive or dysthymia patients. Therefore, when analyzing the results of the improvement of the neuropsychological tests in the follow up visit, this should be taken into consideration.

Conclusions
Depression is a prevalent disease in the elder population. It is important to implement health policies to inform the community, prevent associated risk factors, and promote appropriate treatments and rehabilitation. This condition not only affects the patients but also their environment.