Erik Bertoletti

Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors

BACKGROUND This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimers disease (AD) living at home. METHODS The study was conducted in two different outpatient neurological clinics. 338 patients with probable AD were treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinicians judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs). RESULTS At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change -0.8 +/- 2.3 vs 0.04 +/- 2.9; p = 0.02) and patients depressed and treated with SSRI (mean change -0.8 +/- 2.3 vs 0.1 +/- 2.5; p = 0.03). CONCLUSIONS In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

The Importance of Alzheimer Disease Assessment Scale-cognitive Part in Predicting Progress for Amnestic Mild Cognitive Impairment to Alzheimer Disease

The aim of this study was to verify the usefulness of Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog), in screening participants at risk of developing Alzheimer disease (AD) among populations with amnestic mild cognitive impairment(aMCI). 98 outpatients with aMCI were recruited. Participants were revaluated after 1 year: 44 (44.9%) were progressed to AD (progressors), while 54 (55.1%) did not convert (nonprogressors MCI). At baseline, cognitive performances were more impaired in progressors assessed by MMSE and by a neuropsychological battery. When tested with the ADAS-Cog subscale, the 2 groups of participants at baseline, progressors, and nonprogressors MCI, were significantly different regarding total score, memory, and nonmemory subitems. Considering a cutoff of 9.5 total score, adjusted for education, ADAS-Cog subscale showed a good performance (area under the curve = 0.67; sensitivity = 0.62%; specificity = 0.73%) in predicting conversion from aMCI to AD. Progressors aMCI were characterized at baseline by a greater cognitive impairment. ADAS-Cog subscale is a useful and brief cognitive assessment tool to screen aMCI participants converting to AD within 1 year.

Cognitive and Psychopathologic Response to Rivastigmine in Dementia With Lewy Bodies Compared to Alzheimer’s Disease: A Case Control Study

Cholinesterase inhibitors (ChEIs) are effective in improving cognition and behavior in patients affected by Alzheimer’s disease (AD) as well as by Lewy bodies dementia (DLB). The authors compared the effect of rivastigmine in the treatment of cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) in 30 AD and in 30 DLB patients. At baseline, DLB compared to AD patients showed a greater number of extrapyramidal symptoms (P < .005) and were similar regarding cognitive symptoms and BPSD. After treatment, both groups showed a comparable cognitive and psycho-behavioral improvement. A significant difference between AD and DLB patients was found for hallucinations (P < .002). Rivastigmine produces comparable cognitive benefits in patients with DLB and AD and also a significant improvement of behavioral disorders. These findings support the view that ChEIs should be considered a first-line treatment of the cognitive and psycho-behavioral symptoms of both AD and DLB.

Mild parkinsonian signs and psycho-behavioral symptoms in subjects with mild cognitive impairment

BACKGROUND Mild cognitive impairment (MCI) may be accompanied by extra pyramidal signs (EPS), which are related to the severity and type of cognitive impairment. We aimed to elucidate further the relationship between MCI and EPS, analyzing the correlation between the severity of EPS and cognitive functions, and the presence of EPS and neuro-psychiatric features. METHODS Data were obtained from a longitudinal study of 150 MCI outpatients. Participants underwent a clinical assessment including the Unified Parkinson Disease Rating Scale, the Neuropsychiatric Inventory, the Tinetti Scale, and a standardized neuropsychological battery. Mild EPS could be defined as being present (MCI with mild EPS) using a subscale of UPDRS, based on three specific symptoms: bradykinesia, rigidity and tremor. RESULTS The two groups, one with mild EPS (24%) and one without EPS (76%), differed in gait abnormalities and presence of extrapyramidal symptoms. Groups did not differ in terms of general cognitive functions evaluated using the Mini-mental State Examination, while subjects with MCI with mild EPS performed significantly worse than those with MCI without EPS in total global score and in non-memory items of the Alzheimers Disease Assessment Scale. Moreover, severity of EPS was significantly correlated with low performance on executive functions and with high performance on episodic memory. The group with MCI with mild EPS were observed to have a greater prevalence of patients with anxiety, depression, apathy and sleep disturbances than in MCI without EPS. CONCLUSION MCI may be associated with mild parkinsonian signs, the severity of which are related to the severity of cognitive impairment, in particular of non-memory functions, and to a differential pattern of psycho-behavioral symptoms.

Acetylcholinesterase inhibitors and depressive symptoms in patients with mild to moderate Alzheimer’s Disease

Background and aims: Acetilcholinesterase inhibitor (AChEis) therapy in Alzheimer Disease (AD) has been shown to provide cognitive benefits and to slow progression of the disease. AChEis have also been demonstrated to improve behavioral symptoms, although there seem to be subtle differences in the magnitude of response. The aim of our study was to evaluate the effect of 16 weeks treatment with AChEis on depressive symptoms in a selected sample of AD patients in routine clinical practice. Subjects and methods: A study of 135 patients with Alzheimer’s disease. All subjects were assessed at baseline (upon initiation of AChEis therapy) and re-evaluated after 16 weeks. Results: At baseline, «Depressed» and «Not depressed» patients were categorized according to DSM IV criteria for depression in Alzheimer Disease. After 16 weeks of treatment with AchEis, we observed an improvement of mood in the “Depressed” patients. In this group “Mood symptoms”, measured with GDS, were independently associated with GDS “Mood symptoms” at baseline, but not with improvement on cognition (mean change of MMSE), age or sex. Conclusions: In depressed AD subjects, AChEis treatment improves depressive symptoms evaluated by GDS. This improvement is independent of cognition enhancement.

Serum albumin level interferes with the effect of Donepezil in Alzheimer’s disease

Background and aims: The most successful therapeutic approaches to Alzheimer’s disease (AD) have involved acetylcholinesterase inhibitors (ChEIs). In view of the different response rates to ChEIs therapy, it is important to identify the pharmacokinetic and pharmacodynamic mechanisms which may interfere with this effect. The aim of the study is to evaluate the efficacy on cognition of donepezil, a cholinesterase inhibitor, in a sample of mild to moderate AD patients with various serum albumin levels, a condition modifying drug distribution. Methods: Ninety-eight Alzheimer patients treated with donepezil were analyzed in an outpatient clinic between January 2003 and January 2005. At study entry, participants underwent multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All concomitant illnesses and treatments were recorded. Patients were grouped in three categories (with low, medium and high albumin levels). Results: The total sample of patients showed cognitive improvement from baseline of the ADAS Cog score at three months (ADAS Cog mean change −1.4+5.4; p=0.01), cognitive stabilization at nine (ADAS Cog mean change 0.03+6.7; p=ns), and not statistically significant worsening at fifteen months (ADAS Cog mean change 0.9+7.3; p=ns). The low serum albumin level group was associated with a greater response to donepezil. In fact, cognition, evaluated by the ADAS Cog mean change from baseline, improved during the first 15 months of treatment in the low serum albumin level group, but worsened in the two higher groups. Conclusion: Our preliminary data suggest that serum albumin level should be monitored to evaluate the clinical efficacy of ChEIs therapy.

Does Age at Observation Time Affect the Clinical Presentation of Mild Cognitive Impairment

Background: To date, there are no published data investigating the role of age in the clinical and neuropsychological presentation of mild cognitive impairment (MCI). The aim of the study was to evaluate whether age at the time of evaluation modulates clinical, functional or cognitive profiles in MCI subjects. Methods: A total of 167 outpatients with a clinical diagnosis of MCI were consecutively enrolled and entered in the study. Clinical and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological standardized assessment. Results: MCI subjects were divided into 3 groups according to their age at observation time: 58 MCI patients were classified as young (≤69 years), 89 as old (70–79 years) and 20 as very old (≧80 years). The 3 groups did not differ in demographic characteristics, general cognitive functions and memory impairment. Very old MCI subjects showed a significantly greater impairment than younger MCI patients in cognitive domains involving executive functions. In particular, very old MCI patients were more frequently classified as having multiple-domain amnestic MCI. Conclusion: Present data highlight that the clinical presentation of MCI is affected by age: at presentation, very old MCI subjects show a worse performance than younger MCI subjects on multiple abilities, particularly on executive functions.