Luca Rozzini

Behavioral Syndromes in Alzheimer’s Disease: Description and Correlates

Introduction: Behavioral disturbances in patients with Alzheimer’s disease (AD) are ill-defined conditions. We hypothesize that the many behavioral disturbances hitherto described and studied might be grouped into few syndromes with separate determinants and correlates. Patients and Methods: 162 consecutive patients with probable AD admitted to a dementia unit were assessed by the UCLA Neuropsychiatric Inventory (NPI). Results: Factor analysis was carried out on NPI subscales, leading to three syndromes: ‘mood’, ‘psychotic’ and ‘frontal’. Patients with the ‘psychotic’ syndrome were older, had older age at dementia onset, had poorer cognition, were more often males, and had faster rate of dementia progression. Patients with the ‘frontal’ syndrome had higher education, longer disease duration, and slower rate of progression. Discussion: Some combinations of behavioral disturbances occur more frequently together and might represent separate behavioral syndromes. Different clinical correlates of the syndromes suggest separate etiologies.

Object and action naming in Alzheimer's disease and frontotemporal dementia

To assess noun and verb processing in different dementia types, we tested object and action naming in three groups of subjects: probable Alzheimers disease (AD) with mild to moderate dementia; age- and education-matched normal subjects; and a group of frontotemporal dementia (FTD) patients. AD and FTD patients were impaired in naming compared with control subjects; action naming was more severely impaired. However, the discrepancy between object and action naming was significantly greater in FTD than in AD patients, independent of the severity of dementia or of overall language impairment. The latter finding is compatible with the hypothesis that the frontal lobe plays a crucial role in action naming. A relatively selective impairment in action naming might be a characteristic neuropsychological feature of FTD.

Amyloid precursor protein in platelets A peripheral marker for the diagnosis of sporadic AD

Background: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD. Objective: To evaluate the sensitivity and the specificity of platelet APP forms’ ratio (APPr) as a marker for AD. Methods: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands. Results: Mean APPr levels were decreased in AD patients (mean OD ± SD = 0.35 ± 0.18) compared with the CON group (mean OD ± SD = 0.92 ± 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05). Conclusion: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.

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

ImportancenCerebral 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.nnnObjectivenTo 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.nnnDesign, Setting, and ParticipantsnThe 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.nnnMain Outcomes and MeasuresnPrimary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment.nnnResultsnOf 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 (Pu2009<u2009.001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (Pu2009<u2009.001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (Pu2009<u2009.001; effect size Cohen du2009=u20091.04) and decreased by 29.9% in amyloid-negative (Pu2009<u2009.001; du2009=u2009-1.19) 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 (Pu2009<u2009.001).nnnConclusions and RelevancenAmyloid 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

BACKGROUNDnThis 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.nnnMETHODSnThe 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).nnnRESULTSnAt 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).nnnCONCLUSIONSnIn AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

Results of a multi-level therapeutic approach for Alzheimer's disease subjects in the "real world" (CRONOS project): a 36-week follow-up study.

Background and aims: Recently, the Italian Ministry of Health started a national project (CRONOS project), aiming at assessing how a multi-level therapeutic approach — including 2-year free-of-charge treatment with cholinesterase inhibitors (ChE-I), pharmacologic and non-pharmacologic management of behavioral disorders, periodic multi-dimensional assessment, and informal caregivers’ counseling — performs in subjects with mild-to-moderate Alzheimer’s disease (AD). Five hundred and three Alzheimer Evaluation Units (AEUs) were instituted for this purpose all over Italy. In this paper we present the results of this approach in a large population of AD subjects followed for 36 weeks by 14 AEUs in Eastern Lombardy, Italy. Methods: The project lasted for two years (September 2000-September 2002). Subjects eligible for the CRONOS project had a diagnosis of probable AD, a Mini Mental State Examination (MMSE) score at baseline ranging from 10 to 26, and onset of cognitive disorders between 40 and 90 years of age. Periodic clinical and multi-dimensional assessments, including MMSE, Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were made at 12 and 36 weeks; ChE-I doses, psychotropic and antidepressant drugs were also re-assessed at all clinical examinations. Caregivers were instructed about dementia and drug-related problems. Results: Of the 808 subjects who completed the 36-week follow-up, 441 were naïves (i.e., never previously treated with ChE-I drugs) and 367 non-naïves. At 12 weeks, both naïves (mean variation from baseline= 0.8 points) and non-naïves (mean variation from base-line= 0.5 points) improved their MMSE scores, while at 36 weeks only naïves improved (mean variation from baseline= 0.1) and non-naïves decreased (mean variation from baseline= −1.2). The IADL and ADL scores progressively and mildly declined from baseline to the 36th week (ADL, mean variation from baseline= −0.5 for naïves, −0.3 for non-naïves; IADL= −0.7 for naïves, mean variation from baseline= −0.4). However, when the MMSE, ADL and IADL variations were controlled for age, sex and education, no significant time effect was found (MMSE, Wilks’ lambda p=0.34; ADL, Wilks’ lambda p=0.25; IADL, Wilks’ lambda p=0.3, respectively). These patterns were apparently unrelated to ChE-I doses. Neuroleptic use doubled in naïves and antidepressants increased in both groups. Conclusions: This multi-level therapeutic approach seems to slow down progression in cognitive and functional performance, in both naïve and non-naïve subjects. The possibility of recurrent examinations by specialized physicians, accurate, close management of psychotropic drugs, and informal counseling to caregivers probably aid in achieving such results in a “real world” population of AD elderly subjects living at home. Future studies are needed to assess whether a multi-level therapeutic approach including higher ChE-I dose may perform better in these subjects.