Aristides Kazis

The validation of the short form of the Geriatric Depression Scale (GDS) in Greece

The Geriatric Depression Scale-15 (GDS-15) is a short, 15-item instrument specifically designed to assess depression in geriatric populations. Its items require a yes/no response. The Geriatric Depression Scale was first introduced by Yesavage et al. in 1983, and the short form (GDS-15) was developed by Sheikh and Yesavage in 1986. The aim of the current study was the standardization of the GDS-15 for use in Greece. Subjects were divided into Group A: 168 control subjects, and Group B: 103 patients suffering from clinically diagnosed depression. All were over 65 years of age. A score of 6/7 on the GDS-15 was found to be the best cut-off point for diagnosing depression in an elderly Greek population, with Sensitivity=92.23 and Specificity=95.24. GDS-15 manifests high internal consistency with Cronbach’s alpha=0.94, and all items seem to be equivalent. Factor Analysis of the GDS-15 revealed 4 factors: a cognitive (thought content), an affective, a functional, and a factor that reflects helplessness and fear for the future. The two diagnostic groups differed on all 4 factors scores at p-value <0.001.

Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of a Greek population.

Many efforts have been made to trace the causes of Alzheimers disease (AD). There are, however, many points of controversy among reports from the same country as well as among reports from different countries. The current study is a case-control study to determine the risk factors in the development of AD in Greece. Sixty-five patients with AD and 69 age-matched controls were examined. All patients with AD fulfilled the DSM-IV criteria for AD and NINCDS-ADRDA criteria for probable AD. Demographic characteristics such as gender, current marital status, who he/she is living with, education, main place of residence in childhood, adulthood, and late life, occupational hazards, patients medical history (history of diabetes mellitus and hypertension), life habits like alcohol consumption and smoking, and a history of head trauma, heart attack, stroke, parkinsonism, or depression were collected from the subject or from an informant. A family history of selected diseases (hypertension, diabetes mellitus, dementia, Parkinsons disease, Downs syndrome, stroke) was also elicited. Ages of father and mother at birth were also recorded. Chi-square test, Kruskal-Wallis analysis of variance, cluster analysis, and logistic regression analysis were used for statistical analysis. The results (chi-square test) showed a statistically significant difference between patients with dementia of the Alzheimer type and controls as far as marital status (p = .04), the subjects history of major depressive episode (p = .02), and family history of dementia (p = .002) were concerned. Logistic regression analysis results produced a complex model of family aggregation of dementia, with patients with a history of depression and family history of dementia having an up to seven times higher risk of developing AD. These findings, especially a family history of dementia, are consistent with most of the literature.

Extrapyramidal symptoms and signs in Alzheimer's disease: Pravalence and correlation with the first symptom:

Objectives: To determine the prevalence and clinical correlates of extrapyramidal signs (EPS) in outpatients with probable Alzheimers disease (AD); to examine the appearance of EPS in association with the first symptom that led the patient or family to ask for medical help; to examine the association of the prevalence of EPS with gender, age at onset of the disease, duration of the disease, severity of dementia, functional disability, and potential use of neuroleptics; and to address the issue of the possible role of EPS as a predictive factor for the clinical course of the disease. Patients and methods: We examined 126 patients meeting NINCDS-ADRDA* criteria for probable AD and 29 healthy, nondementia controls of comparable age and gender. Thirteen of the patients taking neuroleptics at the time of the examination were excluded from the main study group and formed a separate subgroup of AD/neuroleptics-positive. Twenty-eight of the AD/neuroleptics-free patients were re-examined during an 18-month period in order to determine the possible role of EPS as a predictive factor of the clinical course of the disease. Results: Only 8 percent of the AD/neuroleptics-free patients were free of EPS, while the corresponding percentage in the control group was 61.5 percent. The most common types of EPS presented in the patient group were hypomimia ([facial mask] 60 percent), difficulty in talking (53.66 percent), bradykinesia (51.4 percent), postural instability (47.33 percent), abnormal gait (34.66), and rigidity (26 percent), respectively. No significant differences were found when examining for the presence of resting tremor, other tremors, dystonias, and dyskinesias. With regard to the presence of EPS and the first symptom, no significant difference was found among patients whose first complaint was memory disorder (probable AD) and patients with other symptoms. When examining the association between the prevalence of EPS and gender or age at onset of the disease, no special correlation was detected. However, such a correlation was found between the prevalence of EPS and duration of the disease, as indicated by the fact that EPS appear in 78.9 percent of the patients with a duration of illness less than two years, but in 97 percent of the patients with a corresponding duration of two years or more. The mean duration of the disease in patients appearing with EPS is found to be 2.68 ± 1.98 years. The presence of EPS increases proportionally with the progression of the disease and cognitive and functional decline. Patients with poor results in the MMSE (score of less than 11) appear to present EPS at a greater percentage than those with better performance on the examination (MMSE scores greater than 11). With regard to the association between EPS and functional ability in AD, it seems that the presence of EPS imposes difficulties in daily activities, as seen by the fact that patients with EPS have lower FRSSD scores (mean ± SD: 14.87 ± 10.53) than patients without EPS (5 ± 2.58). After controlling for duration of the disease, the use of neuroleptics is found to influence the appearance of EPS in patients with AD. Almost all of the patients AD/neuroleptics-positive patients presented EPS (100 percent), while 92 percent of the AD/neuroleptics-free patients manifested such symptoms. Finally, we re-evaluated 28 patients, who were part of the initial AD/neuroleptics-free group, in order to determine whether the appearance of EPS could have prognostic value for the clinical course of the disease. Patients who presented EPS at initial examination appeared to deteriorate faster, mainly cognitively, but also functionally. The mean decrease in MMSE scores in patients with EPS was found to be 2.65 ± 3.46; while in patients without EPS at initial visit, MMSE scores were 0.63 ± 3.88. The functional decline seems to be less influenced by the presence of EPS. The corresponding mean decrease in FRSSD scores of the two groups was 2.1 ± 5.55 and 1.8 ± 2.1, respectively.

Correlation of rCBF (SPECT), CSF tau, and congnitive function in patients with dementia of the Alzheimer's type, other types of dementia, and congrol subjects

Background. The diagnosis of Alzheimers disease (AD) during life remains difficult and a definite diagnosis of AD relies on histopathological confirmation at post-mortem or by cerebral biopsy. It is well known that levels of tau proteins are consistently and significantly increased in the cerebrospinal fluid (CSF) of Alzheimers patients versus levels in normal controls. However, the sole use of this biochemical marker as a test for AD is hampered by mediocre specificity, since tau concentrations may also be elevated in certain other neurological disorders (OND). Studies of the regional cerebral blood flow (rCBF) are widely performed because of their convenience and usefulness in a variety of neurological disorders. Most studies have reported high diagnostic accuracy for brain perfusion single-photon emission tomography (SPECT) in Alzheimers disease. Methods. In order to improve specificity, in this study, correlation of 99mTc-HMPAO SPECT scanning and CSF tau protein levels was made in 117 patients with AD, 67 patients with OND (26 of which had other dementias), and 23 age-matched controls. Means and standard deviations of tau protein levels were 297, 42 ± 221, 12 in AD patients and 78,07 ± 98, 51 in patients with OND (p = 0.0006). No correlation was noted between CSF tau protein levels and age, duration of the disease, and neuropsychological scores of mini-mental state examination (MMSE), Cambridge Cognitive Examination (CAMCOG), and Functional Rating Scale for Symptoms of Dementia (FRSSD). Findings. There was a bilateral parietal and temporal hypoperfusion in patients with AD in SPECT in comparison to normal subjects (p < 0.05) and there was a statistical correlation between this hypoperfusion and neuropsychological tests, such as MMSE and CAMCOG (p < 0.01). There was no correlation between tau protein levels and hypoperfusion in SPECT. Interpretation. Conclusively, the correlation between elevated levels of tau proteins and hypoperfusion in SPECT in AD patients therefore cannot improve the specificity of tests in AD and this means that the determination of CSF tau proteins levels is not a specific diagnostic test for AD.

Epidemiological Dementia Index: A Screening Instrument for Alzheimer’s Disease and Other Types of Dementia Suitable for Use in Populations with Low Education Level

Introduction: MMSE and CAMCOG are neuropsychological scales developed for use in everyday clinical practice and epidemiological surveys. Material and Methods: These two instruments were used as part of the assessment during an epidemiological survey in the municipality of Pylaia, Greece. The project was based on the World Health Organization Program for Research on Aging and Age-Associated Dementias (1992). It had two phases. During phase I, nursing students collected demographic data, risk factors, personal and family history data and they applied MMSE, CAMCOG and scales of everyday life functioning. During phase II, 4 physicians examined all subjects that manifested possible cognitive deterioration (MMSE<27), in order to reach a final diagnosis. The final diagnosis was made according to DSM-IV and NINCDS-ADRDA criteria. MMSE and CAMCOG were not taken into consideration in the diagnostic process. Three hundred and eighty subjects were initially screened. All were aged over 70 years. After the exclusion of subjects who were illiterate, blind, etc., the results of 277 subjects were finally analyzed. Subjects with 6 years of education or less accounted for 92.42% of the total study sample. Twelve of them (5.33%) suffered from Alzheimer’s disease, 7 from vascular dementia (2.52%) and 1 suffered from secondary dementia (0.36%). Results: MMSE exceeded 90% sensitivity at the level 22/23 and specificity at 14/15. The levels for CAMCOG were 56/57 and 43/44, respectively. This low performance of both tests is to a large extent due to the functional illiteracy of elderly individuals in Greece, to possible coexistence of mood disorders or simply to lack of cooperation. The analysis of data led to the development of an Epidemiological Dementia Index (EDI), with a scale ranging from 0 to 7. Nondemented subjects had a mean EDI of 5.12 (SD = 1.67) and demented patients had a mean EDI of 1.6 (SD = 1.92). At the level 4/5 sensitivity was 93.33. Specificity was 93.56 at the level 2/3.

Greek validation of the seven-minute screening battery for Alzheimer's disease in the elderly.

The increasing prevalence of Alzheimers disease (AD) suggests that there is an increasing need for accurate and easily administered screening instruments. The Seven-Minute Screen is a neurocognitive screening battery consisting of four brief tests (enhanced cued recall, temporal orientation, verbal fluency, and clock drawing). We studied 55 outpatients with probable AD, 40 healthy volunteers of comparable age, sex, and education and 31 elderly patients with other neuropsychological disorders. The aim of our study was to determine the validity and reliability of this test. Differences on individual tests were evaluated using the Student t test. (Recall: 6.4 ± 5.02/15.38 ± 0.95; Orientation: 48.76 ± 42.74/0.2 ± 0.52; Verbal: 8.2 ± 4.94/18.05 ± 4.63; Clock drawing: 2.07 ± 2.56/6.03 ± 11.25 for AD patients and control subjects, respectively). Mean scores for patients with AD and control subjects on all four individual tests were significantly different (for each, p < 0.001). The mean time to complete the test for healthy control subjects was nine minutes and 18 seconds, for neuropsychological disorders nine minutes and six seconds, and for AD patients 13 minutes and 32 seconds (p < 0,001). Logistic regression analysis was used to determine the degree to which the battery discriminated between control subjects and patients with AD (sensitivity 92.73 percent and specificity 97.50 percent). We then separated the patients with MMSE > 20 and the same model of regression analysis was used. Sensitivity was 81.25 percent and specificity was 96.55 percent using 0.7 as the cutoff probability, and 93.75 and 96.55 percent, respectively, using 0.5 as the cutoff probability. Neither age nor education and gender had an effect on the results. The Seven-Minute Screen appears highly sensitive to AD patients and may be useful in helping to make initial distinctions between patients with early dementia and normal elderly.

The Cambridge Cognitive Examination (CAMCOG): A validation study in outpatients suffering from dementia and non-demented elderly subjects (including Age Associated Cognitive Decline patients) in Greece:

Introduction: The Cambridge Cognitive Examination for the elderly (CAMCOG) was first published in 1986 as a reliable instrument for the study of patients with cognitive function impairment. Objective: To standardize the Greek version of CAMCOG. Setting: Dementia Outpatient Clinic, 3rd Department of Neurology, Aristotle University of Thessaloniki. Participants: 150 nondemented controls and 100 patients suffering from mild to severe dementia of various types took part in the study. Results: CAMCOG manifests Cronbachs alpha=0.93. In the group of patients under 75, sensitivity (Sn) is 90.00 percent at the level of 76/77 and specificity is 91.89 percent at the level of 70/71. The respective scores for the group of patients over 74 are 68/69 (Sn=90.00 percent) and 60/61 (Sp=92.30 percent). It seems that CAMCOG shows an “uncertainty zone” in both groups between the scores of 71 to 76 for the first group and of 61 to 68 for the second. The MMSE cut-off point, for the two groups are 23/24 (Sn=94.28 percent, Sp=90.99 percent) and 22/23 (Sn=96.60 percent, Sp=94.87 percent), respectively. Conclusion: The Greek version of CAMCOG manifests different properties than the original British Version. This is probably due to differences in education and social background (e.g., cultural isolation of rural areas). MMSE performs better than CAMCOG mainly because diagnosis is based on the assessment of fundamental aspects of cognitive function, which is reflected in MMSE in a way that is less affected by the mental or educational status of the subject.

Validation of the epidemiological dementia index in geriatric outpatients.

UNLABELLED The aim of the current study was to test the properties of a scale especially developed for use in epidemiological surveys in low sociocultural populations, and to determine whether this scale can be used in a clinical population. MATERIAL AND METHODS Two hundred fifty subjects took part; 150 were controls and 100 had dementia of various types according to DSM-IV and NINCDS-ADRDA criteria. RESULTS Cronbachs alpha was equal to .78. In the group of people under 75 years old, sensitivity did not exceed 90%. Specificity was over 90% at the level 4/5. The respective scores for the group of people over 74 were 6/7 and 3/4. DISCUSSION The Epidemiological Dementia Index seems to be less powerful when used in a clinical population. This provides further evidence that it is not suitable to use the same instruments in both epidemiological studies and clinical practice.

Borjeson-Forssman-Lehmann syndrome: two severely handicapped females in a family

We report on a case of Borjeson-Forssman-Lehmann syndrome (BFS) in which two sisters appear with the clinical picture of severe mental handicap, dysmorphic features and grand mal seizures. Their mother presents the above symptomatology in a milder degree. It is one of the few reports in literature where females develop BFS in its typical clinical form.

Target symptoms for fluvoxamine in old age depression

INTRODUCTION: Old age depression is difficult to treat. It is presumed that the underlying biochemical mechanism differs from that of depression of younger age. Clinical manifestations also differ, as elderly people manifest more irritability, anxiety, conduct and cognitive disorders than pessimism or guilt. Response to treatment is believed to be poorer than in younger patients. METHOD: Fifty patients, with a mean age of 66.65, suffering from major depression or dysthymia according to DSM-IV criteria, took part in the study. Their mean HDRS score was 16.77. They were prescribed 100 mg of fluvoxamine daily. Half of them returned 3 months later for reassessment by GDS, HDRS, MMSE, CAMCOG and FRSSD. RESULTS: Mean changes in scores were: GDS, -3.14 +/- 10.86; MMSE, -0.96 +/- 3.34; CAMCOG, +1.59 +/- 8.95; and FRSSD -3 +/- 4.96; statistically significant differences were found for GDS and FRSSD scores. All patients manifested residual symptoms. CONCLUSION: Fluvoxamine improved elderly patients suffering from g...INTRODUCTION: Old age depression is difficult to treat. It is presumed that the underlying biochemical mechanism differs from that of depression of younger age. Clinical manifestations also differ, as elderly people manifest more irritability, anxiety, conduct and cognitive disorders than pessimism or guilt. Response to treatment is believed to be poorer than in younger patients. METHOD: Fifty patients, with a mean age of 66.65, suffering from major depression or dysthymia according to DSM-IV criteria, took part in the study. Their mean HDRS score was 16.77. They were prescribed 100 mg of fluvoxamine daily. Half of them returned 3 months later for reassessment by GDS, HDRS, MMSE, CAMCOG and FRSSD. RESULTS: Mean changes in scores were: GDS, -3.14 +/- 10.86; MMSE, -0.96 +/- 3.34; CAMCOG, +1.59 +/- 8.95; and FRSSD -3 +/- 4.96; statistically significant differences were found for GDS and FRSSD scores. All patients manifested residual symptoms. CONCLUSION: Fluvoxamine improved elderly patients suffering from geriatric depression, particularly in respect of depressive thought content (GDS) and impairment in everyday activities (FRSSD). When cognitive impairment due to depression was present, response to treatment was greater. Severely depressed patients showed a greater response to treatment, but also more severe residual symptoms. (Int J Psych Clin Pract 2000; 4:127-134) 3.17 +/- 4.06; HDRS,