Marta Conti

Odor Identification Deficit Predicts Clinical Conversion from Mild Cognitive Impairment to Dementia Due to Alzheimer's Disease

The aim of this study was to analyze the relationship between olfactory and cognitive functions in subjects affected by mild cognitive impairment (MCI) and to investigate whether olfactory deficits might reflect the likelihood of conversion from MCI to dementia. In this longitudinal study conducted on a sample of MCI outpatients, CA-SIT Smell Identification Test was administered to 88 MCI subjects and 46 healthy control subjects. MCI subjects have been divided into two groups, considering smell identification performances: 40% had normal performances (MCI olfactory-normal), whereas 60% had a moderate olfaction deficit (MCI olfactory-impaired). At 2-year follow-up, the 47% of MCI olfactory-impaired subjects and the 11% of MCI olfactory-normal subjects progressed to dementia. In a logistic regression model, a lower score in MMSE (95%, OR 1.9; IC 1.23-3.01; p = .004) and a pathological smell identification at baseline (95%, OR 5.1; IC 1.16-22.6; p = .03) were independently associated with the progression to dementia within 2 years. This study confirms that smell identification testing may be useful in high-risk settings to identify patients at risk for developing dementia.

Differential Impact of Apathy and Depression in the Development of Dementia in Mild Cognitive Impairment Patients

Background and Aims: Neuropsychiatric symptoms may accompany mild cognitive impairment (MCI) and assist in identifying incipient dementia. The aim of this study was to evaluate the role of apathy and depression in the conversion to dementia among MCI subjects. Methods: 124 MCI outpatients were investigated. Diagnosis of apathy and depression was based on clinical criteria. The main endpoint was the development of dementia within 2 years from the enrolment. Results: 50 (40.3%) subjects were classified as MCI normal, 38 (30.7%) as MCI depressed, 21 (16.9%) as MCI depressed-apathetic and 15 (12.1%) as apathetic. The rates of conversion were 24% for MCI normal, 7.9% for MCI depressed, 19% for MCI depressed-apathetic and 60% for MCI apathetic. Diagnosis of apathy was a risk factor for conversion apart from age, functional and cognitive status at baseline (OR = 7.07; 95% CI 1.9–25.1; p = 0.003). In contrast, MCI depressed subjectshad a reduced risk of conversion (OR = 0.10; 95% CI 0.02–0.4; p = 0.001). Conclusion: These findings argue for a differential role of apathy and depression in the development of dementia, and suggest the need of dissecting in MCI patients apathy and depression symptoms in the reading of mood disorders.

Anxiety symptoms in mild cognitive impairment

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.

Neuropsychiatric Symptoms in Amnestic and Nonamnestic Mild Cognitive Impairment

Background: The information regarding neuropsychiatric symptoms in the subtypes of mild cognitive impairment (MCI) is inadequate. Objective: To describe the behavioral neuropsychiatric symptoms of MCI in two subgroups of MCI patients with different neuropsychological characteristics. Methods: MCI patients are classified as amnestic (aMCI) if they have a prominent memory impairment, either alone or with other cognitive impairments (multiple domains with amnesia), or nonamnestic (naMCI) if a single nonmemory domain is impaired alone or in combination with other nonmemory deficits (multiple domains without amnesia). The Neuropsychiatric Inventory (NPI) was administrated to detect behavioral and psychological disturbances observed by the caregiver. Results: 120 subjects were analyzed: 94 were classified as aMCI and 26 as naMCI. Subjects with aMCI were more compromised than those with naMCI on global cognitive functions. About 85% of MCI patients had some neuropsychiatric symptoms evaluated with the NPI and the most prevalent symptom was depression, followed by anxiety. A significantly higher prevalence of hallucinations and sleep disorders has been observed in the naMCI group in comparison with the aMCI group. Conclusion: Neuropsychiatric symptoms occur in the majority of persons with MCI and may be the earliest manifestation of different diseases, each one associated with different clinical profiles at the stage of MCI.

Assessment of the incremental diagnostic value of florbetapir F 18 imaging in patients with cognitive impairment: The incremental diagnostic value of amyloid PET with [18F]-florbetapir (INDIA-FBP) study

Importance Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. Objective To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. Design, Setting, and Participants The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. Main Outcomes and Measures Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. Results Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). Conclusions and Relevance Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

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.

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.