Faculty Bibliography

The term 'mirror sign' refers to the inability to recognize the reflection of oneself in a mirror, while the ability to recognize others' faces often remains intact. In this article, we present a case of an 85-year-old woman, with probable Lewy body dementia, who stably exhibited a delusional 'mirror sign' for a period of 9 months. Following a straightforward, ecological, non-pharmacological intervention, her 'mirror sign' delusion was no longer present.

Background: In hypertension (HTN), cerebral blood flow (CBF) regulation limits are changed and the blood pressure (BP) threshold at which CBF is safely maintained is higher. This shift may increase the brain's vulnerability to hypoperfusion at lower BP. Despite growing recognition of the link between hypoperfusion and neurodegeneration little is known about whether blood pressure reductions can induce deficient perfusion and promote expression of cerebrospinal fluid (CSF) biomarkers of amyloid and neurofibrillary pathology. We investigated the relationship between longitudinal changes in mean arterial pressure (MAP) and CSF biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with and without HTN. Methods: Longitudinal assessments of blood pressure (MAP), CSF ptau181 (phosphorylated tau), total tau, amyloid beta 1-42 (Abeta42), cognition and whole brain volume were conducted on average 2.060.6 years apart in a group of 77 cognitively healthy elderly (age 63.469.4, range 44-86 years; education 16.962.1, range 10-22 years; 60% women). MAP was calculated as: 1/3 systolic blood pressure + 2/3 of diastolic blood pressure. Results: At baseline HTN was found in 23 individuals (30%). When longitudinal change (y) in p-tau181 was predicted with theyMAP, HTN, and the HTNxyMAP interaction, both the total model (F 3,73=3.9, p=.01), and the interaction term (p=.01) were significant. These data indicate that the relationship between yMAP and yp-tau181 was strongly dependent on the presence or absence of HTN. Only in the HTN group was a decrease in MAP from baseline to follow-up related to an increase in p-tau181 (r=-0.5 p=.01). In addition, only among subjects with HTN, was a reduction in MAP related to the worsening of verbal episodic memory (r=0.46 p=.03). Finally in the entire group the increase in p-tau181 was associated with reduction in the verbal episodic memory score (beta=-.223, p=.048). No relationship was observed between changes in MAP and whole brain volume. Conclusions: In subjects with HTN, MAP reduction is associated with increased CSF p-tau181 and deterioration of episodic memory, possibly resulting from suboptimal perfusion and subsequent accumulation of neurofibrillary tangles. Prior experimental work has demonstrated a relationship between perfusion, energetic reductions and tauopathy

Background: The regulation of CSF Abeta42 is poorly understood. Recent studies show Abeta42 levels affected by sleep, stress, diet, depression, ApoE genotype, white matter lesions (WML), and Abeta plaques. The purpose of this study was to examine the heterogeneity of Abeta42 as related to ApoE genotype when interacting with known AD risk factors in healthy, cognitively normal subjects. Methods: In cross-section, we examined the Abeta42, T-Tau and P-tau levels as predicted by ApoE4 status in its interaction with depressive symptoms (HAM-D), MRI white-matter hyperintensity volume (WMH V), and memory (Wechsler Logical-Memory). We studied 41 ApoE4+ and 71 ApoE4- subjects (mean age 62.0 6 11.9). All participants were non-depressed (HAM-D-10), cognitively normal (CDR = 0) and free of MRI brain pathology. Results: ApoE4+ subjects compared to the ApoE4- had lower levels of Abeta42 (442 6 27 vs. 603 6 22 ng/L; P <0.01), higher levels of T-Tau (289617 vs. 229613 ng/L; P <0.01), higher p-Tau (2861.6 vs. 17 6 21.9ng/L; P <0.01) and higher WMHv (3.77 6 0.41 vs. 2.67 6 0.32 cm 3, P<0.05). Predicting CSF Abeta42 levels, controlling for age, we observed three significant 2-way interactions: ApoE genotype X mood, ApoE genotype X memory, ApoE genotype X WMH V (F-values range = 4.03-12.35, P<0.05). No interactions were seen for T-tau or P-Tau. Among ApoE4-, mood symptoms, and to a lesser extent worse memory, had a negative correlation with Abeta42 (r = .-44, n = 71, P <0.01 and r = -.22, n = 71, P = 0.07). Among ApoE4+ there was a negative correlation between Abeta42 and WMH V (r = -0.45, n = 26, P<0.05). Conclusions: This is the first study to report the effect of multiple risk factor interactions on CSFAbeta42 levels in cognitively normal subjects with different ApoE4 alleles. Our results indicate that the relationship between risk factors and CSF Abeta42 is dependent on the presence/absence of ApoE4. E4 carriers show reduced CSF Abeta42, and lower Abeta42 was associated with more MRI-WML whereas a more typical clinical AD-type phenotype (poor memory, minor depressive symptoms), was associated with decreased CSF Abeta42 levels in the ApoE4-non-carriers. These data suggest that Apoe4 carriers and noncarriers may offer divergent trajectories of brain and symptom changes. A better knowledge of the presymptomatic early stages of AD and the interactions with the ApoE4 allele may help us understand the variability of our CSF biomarker measures

The Alzheimer Center Reina Sofía Foundation (ACRSF) was envisaged to address the complex and multi-disciplinary research and care needs posed by Alzheimer's disease (AD) and other neurodegenerative dementias. Patients may be admitted at ACRSF either as inpatients (i.e., nursing home) or outpatients (i.e., day-care center). The research program includes clinical, social, biochemical, genetic, and magnetic resonance investigations, as well as brain donation. We present the inception of the clinical research protocol for the ACRSF, the early results, and the amendments to the protocol. Foreseen as distinct populations, inpatient and outpatient results are presented separately. Data were collected from 180 patients (153 inpatients, 27 outpatients) (86% AD), with informed consent for participation in the research program of the ACRSF. Most patients (95%) had moderate to severe dementia. Nursing home patients were older, displayed marked gait dysfunction, and were significantly more dependent in the activities of daily living (ADL), compared to the day-care patients (p < 0.05). Some cognitive, ADL, and quality of life (QoL) scales were eliminated from the protocol due to floor effect or lack of specificity of contents for advanced dementia. New measurements were added for evaluation of cognition, apathy, agitation, depression, ADL, motor function, and QoL. The final assessment is expected to be sensitive to change in all the clinical aspects of advanced degenerative dementia, to promote multidisciplinary and, desirably, inter-center collaborative research and, eventually, to contribute to the improvement of treatment and care for these patients.

OBJECTIVE: To evaluate the prevalence, clinical features, and comorbidities of restless legs syndrome (RLS) among psychogeriatric patients in an out-patient clinical setting. METHODS: Cross-sectional study of a sample of 100 non-demented psychogeriatric outpatients that were assessed for the presence of RLS using the Revised International Restless Legs Syndrome Study Group criteria and other support criteria. Medical and psychiatric illnesses, drug treatments, and other risk factors for RLS were documented. RESULTS: Prevalence of definite RLS in our sample was 11.11% with an additional prevalence of 10.10% of possible RLS. None of these patients had received a diagnosis of RLS previously. RLS was associated with major depressive disorder and with hypertension, but not with other previously described risk factors as female gender, some medical conditions, or psychoactive drug treatments. CONCLUSIONS: RLS is a frequent condition in psychogeriatric patients, especially among those with depression, and is commonly underdiagnosed and undertreated. Clinicians should routinely ask for RLS symptoms when assessing their patients in their regular clinical practice.

Often viewed as a potential tool for preclinical diagnosis in early asymptomatic stages of Alzheimer's disease (AD), the term 'endophenotype' has acquired a recent popularity in the field. In this review, we analyze the construct of endophenotype-originally designed to discover genes, and examine the literature on potential endophenotypes for the late-onset form of AD (LOAD). We focus on the [18F]-fluoro-2-deoxyglucose (FDG) PET technique, which shows a characteristic pattern of hypometabolism in AD-related regions in asymptomatic carriers of the ApoE E4 allele and in children of AD mothers. We discuss the pathophysiological significance and the positive predictive accuracy of an FDG-endophenotype for LOAD in asymptomatic subjects, and discuss several applications of this endophenotype in the identification of both promoting and protective factors. Finally, we suggest that the term 'endophenotype' should be reserved to the study of risk factors, and not to the preclinical diagnosis of LOAD

BACKGROUND: Apathy is an important and distressing behavioural symptom in Alzheimer's disease and in various neuropsychiatric disorders. Recently, diagnostic criteria for apathy have been proposed. OBJECTIVES: In groups of patients suffering from different neuropsychiatric diseases, (i) to estimate the prevalence of patients meeting the proposed diagnostic criteria; (ii) to estimate the concurrent validity of the criteria with the neuropsychiatric inventory (NPI) apathy item; (iii) to identify the most frequently met criteria or sub-criteria in each specific neuropsychiatric disease and (iv) to estimate the inter-observer reliability of the diagnostic criteria for apathy. METHODS: This cross-sectional, multicentric, observational study was performed on 306 patients. Each of the participating centres had to check the presence of apathy according to the diagnostic criteria for apathy in consecutive patients belonging to the following diagnoses list: Alzheimer disease (AD), mixed dementia, mild cognitive impairment (MCI), Parkinson's disease (PD), Schizophrenia (DSM-IV) and major depressive episode. In addition to the clinical interview, the assessment included the Mini Mental Score Examination (MMSE) and the NPI. At the end of the visit, clinicians were required to check the diagnostic criteria for apathy. RESULTS: Using the diagnostic criteria for apathy, the frequency of apathy was of 53% in the whole population, 55% in AD, 70% in mixed dementia, 43% in MCI, 27% in PD, 53% in schizophrenia and 94% in major depressive episode. In AD, mixed dementia, MCI and PD, the NPI apathy score was significantly higher for patient fulfilling the apathy criteria. Goal-directed cognitive activity (criteria B2-Cognition) was the most frequently observed domain followed by goal-directed behaviour (criteria B1-Behaviour) and emotion (criteria B3), respectively. Inter-rater reliability was high for the overall diagnostic (kappa coefficient = 0.93; p = 0.0001) and for each criteria. CONCLUSION: This study is the first one to test the diagnostic criteria for apathy in clinical practice. Results make the diagnostic criteria useful for clinical practice and research