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 Alzheimer's 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 clinician's 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.

Anxiety symptoms in mild cognitive impairment.

INTRODUCTION: Anxiety disorders are less well studied in elderly people than other disorders such as depression. In particular the diagnosis of anxiety is more difficult in patients with Mild Cognitive Impairment (MCI) since the current definition of MCI does not mention neuropsychiatric symptoms. OBJECTIVES: To validate the Italian version of Geriatric Anxiety Inventory (GAI), an instrument that measures dimensional anxiety in elderly people, and assess whether MCI subjects with anxiety symptoms show different neuropsychological profiles in comparison with MCI without anxiety symptoms. METHODS: Fifty-seven outpatients with MCI were consecutively recruited. All patients were assessed using a complete neuropsychological battery to detect the cognitive impairment, and the GAI for the presence of anxiety symptoms. RESULTS: Anxiety + patients (GAI >or= 10) show more behavioral and psychological disturbances than patients with Anxiety- (GAI < 10); in particular they had more agitation, anxiety, depression and more sleep disorders. Moreover, Anxiety + patients are more compromised on instrumental daily functions and on executive functions evaluated with Trail Making B test (TMB). Linear Regression analysis was completed to estimate the coefficients of the linear equation, involving neuropsychological, psychobehavioural and functional characteristics: the executive functions (TMB) are the only variable independently related to the presence of anxiety disturbances. CONCLUSIONS: Executive functions are independently related to anxiety disorders in MCI patients. We hypothesized that the strict interaction between anxiety symptoms and executive functions could depend on specific pathological features at the level of caudate nucleus characterizing early phases of dementia.

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.

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 Alzheimer's 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.

Conversion of amnestic Mild Cognitive Impairment to dementia of Alzheimer type is independent to memory deterioration.

BACKGROUND: Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD. AIM: To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI). METHODS AND MATERIALS: One hundred nineteen subjects consecutively recruited who met the operational criteria for aMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow-up, were defined as Stable. RESULTS: Demented MCI (N = 40; 33.6%) were older (mean age 73.5 +/- 8.5 vs. 69.2 +/- 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (mean score 10.7 +/- 3.9 vs 6.7 +/- 3.4; p = .000) and by MMSE (mean score 26.1 +/- 1.9 vs. 27.3 +/- 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 +/- 0.4 vs 0.1 +/- 0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.7 +/- 0.8 vs. 0.1 +/- 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p =0 .000) respect to Stable. Logistic regression analysis revealed that ADAS-Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD. CONCLUSIONS: In subjects with aMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow-up.

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.

Efficacy of cognitive rehabilitation in patients with mild cognitive impairment treated with cholinesterase inhibitors.

BACKGROUND: Individuals who have Mild Cognitive Impairment (MCI) may be in a transitional stage between aging and Alzheimer's disease (AD). The high rate of conversion from MCI to AD makes early treatment an important clinical issue. Recent evidence suggests that cognitive training intervention may reduce the rate of progression to AD. OBJECTIVES: To evaluate the efficacy of a NeuroPsychological Training (TNP) in patients with MCI who are treated with cholinesterase inhibitors (ChEIs), compared with patients MCI treated only with ChEIs and patients not treated, in a longitudinal, one year follow-up study. METHODS: One year longitudinal and retrospective comparison study of neuropsychological performances in 59 subjects affected by Mild Cognitive Impairment (MCI) according to Petersen's criteria. Fifteen subjects were randomised to receive TNP plus cholinesterase inhibitors; 22 subjects cholinesterase inhibitors alone and 22 subjects no treatment. All the subjects referring memory complaints, corroborated by an informant, underwent a multidimensional assessment concerning neuropsychological, behavioural and functional characteristics, at baseline and after one year follow-up. RESULTS: Subjects without treatment maintained their cognitive, functional and behavioural status after one year; patients treated only with ChEIs improved in depressive symptoms whereas subjects treated with TNP and ChEIs showed significant improvements in different cognitive areas, such as memory, abstract reasoning and in behavioural disturbances, particularly depressive symptoms. CONCLUSIONS: A long-term TNP in ChEIs-treated MCI subjects induces additional cognitive and mood benefits.

Predictors of institutionalization in demented patients discharged from a rehabilitation unit.

BACKGROUND: The decision to place a patient with dementia in long-term care is complex and based on the patient's and the caregiver's characteristics, and on the sociocultural context. Most studies assessing predictors of nursing home placement focused primarily on the characteristics of either the patient, such as dementia severity and difficult behaviors, or the caregiver, such as subjective burden and health status. However, only a few studies comprehensively investigated how both a caregiver's and a patient's characteristics influence nursing home placement. OBJECTIVE: To identify the patient's and the caregiver's characteristics that influence discharge to a nursing home in demented patients consecutively admitted to an intermediate care setting. METHODS: Observational study of 214 patients with dementia consecutively admitted to a Rehabilitation Unit for Dementia in Northern Italy (length of stay 35.1 +/- 14.9 days). The main evaluated outcome was the final destination (home vs nursing home). RESULTS: In a multivariate logistic regression analysis, adjusted for age, gender, cognitive status, and behavioral disturbances, 4 predictors were associated with nursing home placement: living alone (OR 8.79, 95% CI 2.33-33.16; P = .001), degree of dementia severity (CDR, OR 1.69, 95% CI 1.02-2.83; P = .04), compromised functional status (Barthel index admission, OR 3.15, 95% CI 1.05-9.48; P = .04), and caregiver's burden (CBI, OR 2.89, 95% CI 1.15-7.29; P = .02). CONCLUSIONS: Data suggest that living alone, patient's functional impairment, severity of dementia, and caregiver's burden were independent predictors of institutionalization. The interaction between a patient's and a caregiver's characteristics has an important effect on the rate of nursing home placement in demented patients.

Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression of amnestic mild cognitive impairment.

BACKGROUND: Predictors of progression to dementia in individuals with mild cognitive impairment (MCI) define different groups with higher risks of progression. To date, efforts to differentiate those who will progress to dementia from those who will not have proved inconclusive, and while grades of risk have been identified, their generalizability is not clear. AIM: To examine the clinical and socio-demographical risk factors for progression of memory decline in a sample of subjects with referred memory complaints who met criteria for amnestic MCI. METHODS AND MATERIALS: Seventy-four subjects consecutively recruited who met the operational criteria for amnestic MCI. They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after one year. Memory decline was defined using the short story mean score change (at follow-up and at baseline). Subjects showing memory decline, with or without conversion to AD over time, were classified as having progressive MCI; subjects that remained unchanged or improved during follow-up were considered as having stable MCI. RESULTS: Subjects with progressive MCI (n = 39, 53%) were older (p = <0.001) and more educated (p = 0.01) compared to stable MCI (n = 35, 47%) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (p = 0.05). Antihypertensive drug prescription was greater in the stable MCI compared to progressive MCI (p = 0.01) and significant higher levels of plasma total homocysteine were observed in progressive MCI (p = 0.03). When analyzed in a logistic regression model, the prescription of Angiotensin Converting Enzyme Inhibitors (ACE) was found to be independently associated to the stability of cognitive function, whereas older age, higher education, higher levels of plasma total homocysteine and total ADAS-Cog basal score were independently associated with the progression of cognitive decline. CONCLUSIONS: Older age, higher education, poor global cognitive performance, higher levels of plasma total homocysteine are independently associated with the progression of memory decline while the prescription of ACE Inhibitors is a protective factor for cognitive deterioration.