Accelerated long-term forgetting: from subjective memory decline to a defined clinical entity.

Subjective memory decline (SMD) might represent the preclinical phase of Alzheimer's disease (AD), and has been reported in epileptic amnesia associated with accelerated long-term forgetting (ALF). We investigated ALF in SMD subjects by means of RAVLT recall and recognition and ROCF recall after 1-week retention and compared with a control group. Two-way ANOVAs for RAVLT and ROCF were conducted, and stepwise regression analysis was administered considering EMQ and DASS-21 as factors. SMD subjects performed significantly worse than controls at 1-week delay on RAVLT recall and recognition, but not on ROCF, and not associated with depression or memory complaints. SMD patients showed ALF, which is usually associated with temporomesial dysfunctions, representing a cognitive marker to assess objectively memory problems in SMD, and to undisclose initial neurodegenerative disease involving temporal structures usually compromised in AD. Therefore, SMD might no longer be "subjective," but rather a specific and defined clinical entity.

Psychometric properties of the Caregiver's inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia.

OBJECTIVES: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D). DESIGN, SETTING AND PARTICIPANTS: The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales. The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach's alpha (α), Pearson's correlation and ROC analysis, respectively. RESULTS: The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α= 0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57). CONCLUSION: The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor caregiver-reported ecological data in both clinical and research settings.

Improving Amnesia Diagnostic Accuracy with RAVLT Single Scores and Composite Indices: Italian Normative Data.

OBJECTIVE: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used verbal memory measure that provides scores for different aspects of memory. It involves repeated auditory presentation and recall of a 15-item word list (List A) followed by presentation and recall of a distractor list (List B) and then un-cued immediate and delayed recalls (at 15 min and 1 week) of List A as well as recognition testing. Aims of this study are to provide Italian normative data for certain RAVLT Scores and Composite Indices to improve the diagnostic accuracy of the test in clinical settings and to provide further evidence on how RAVLT can differentiate different amnesia profiles due to focal lesions. METHODS: We enrolled 440 healthy participants and RAVLT Single Scores and Composite Indices have been analyzed by means of multiple regression to verify the influence of age, education, and gender. RESULTS: We computed the best linear models with RAVLT Single Scores and Composite Indices, as dependent variables, and the most suitable transformation of independent variables. By reversing the signs of the regression coefficients, the adjustment factors for each level of age and, if needed, education and gender have been computed and the adjusted scores have been standardized into Equivalent Scores. CONCLUSION: Using these standardized measures, we differentiate three profiles of amnesia due to selective hippocampal sclerosis with severe encoding deficit, fornix lesions with source memory problems, and temporal lobe epilepsy with consolidation failure.

Late-onset obsessive-compulsive disorder as the initial manifestation of possible behavioural variant Alzheimer's disease.

INTRODUCTION: A late-onset obsessive-compulsive disorder (OCD) might be a challenging diagnostic issue because of the overlapping with the dementia conditions more related to frontal lobe pathology. We aim to describe and investigate how this condition might represent the isolated long-lasting symptomatology of a frontal Alzheimer's disease (AD). METHODS: An elderly woman with normal cognitive status showed a subacute onset of OCD with contamination obsession and washing compulsion. We conducted neuropsychological assessments and neuroimaging examinations at the onset and at 3-years follow-up. RESULTS: At 3-years follow-up, the patient developed cognitive deterioration, frontal behavioural disorders and improvement of OCD. Cognitive assessment showed impairments of executive functions, episodic memory, and constructional apraxia, according to the involvement of fronto-mesial, temporal and parietal regions at neuroimaging. A clinical diagnosis of possible behavioural variant AD was assigned. CONCLUSION: A typical OCD might be the long-lasting initial manifestation of a possible behavioural variant AD due to dysfunctions of the anterior cingulate network.

Progressive aphasia, apraxia of speech and agraphia in corticobasal degeneration: A 12-case series clinical and neuropsychological descriptive study.

BACKGROUND: Despite initial underreporting of language dysfunctions in corticobasal syndrome (CBS), aphasia is now recognized as a frequent feature of this disease. Aphasia in CBS seems clinically overlying to a non-fluent/agrammatic primary progressive aphasia (nfaPPA), which is also a clinical phenotype associated with corticobasal degeneration (CBD) pathology. However, the clinical features of aphasia in CBS still remain poorly delineated, resulting in misjudgements in the differential diagnosis from a PPA presentation of the disease. AIMS: To investigate the language disorders of this syndrome, also through a systematic examination of recoding skills (reading, written spelling and repetition) and articulatory disturbances, which have been rarely examined in previous studies. METHODS & PROCEDURES: We present a clinical and neuropsychological descriptive study of the language impairments in a case series of 12 aphasic patients with a clinical diagnosis of CBS. Language assessment was conducted by means of the Esame NeuroPsicologico dell'Afasia, a comprehensive Italian battery for language functions, the Token Test, and the Apraxia of Speech Rating Scale. OUTCOMES & RESULTS: The language profile of the patients showed a severe expressive language disorder, characterized by non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding and defective sentence repetition. Severe limb apraxia, visual-spatial deficit and alien hand syndrome were also present. Neuroimaging showed bilateral left asymmetric atrophies and hypometabolism in the frontal premotor, parietal posterior and temporal areas. CONCLUSIONS & IMPLICATIONS: These findings suggest that aphasia in CBS might present as a 'mixed PPA', instead of an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA, associated with AoS, stuttering and agraphia, which might be additional important cognitive markers for the clinical diagnosis of CBS and discriminating features of an nfaPPA presentation of a CBD. These results might also suggest specific intervention areas in the rehabilitation of patients with CBS. What this paper adds What is already known on the subject Language disorders in CBS patients usually present clinically overlying to an nfaPPA, which is also a clinical phenotype associated with CBD pathology, according to recent diagnostic criteria. However, the clinical features of aphasia in CBS still remain poorly delineated, and this raises difficulties and misjudgements for clinicians in the differential diagnosis from a PPA presentation of the disease. What this paper adds to existing knowledge This study shows that the language profile of our CBS patients was characterized by severe expressive language disorders, with non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding, and defective sentence repetition. These findings suggest that aphasia in CBS might present as a 'mixed PPA', rather than an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA associated with AoS, stuttering and agraphia. What are the potential or actual clinical implications of this work? These results suggest that AoS, stuttering and agraphia might be important additional cognitive markers for the clinical diagnosis of CBS, and discriminating features of an nfaPPA presentation of a CBD. The language disorders exhibited in the present study might also support speech and language therapists in targeting specific intervention areas in the rehabilitation of patients with CBS.

Spect-neuropsychology correlations in very mild Alzheimer's disease and amnesic mild cognitive impairment.

BACKGROUND: The purpose of this study was to explore the clinical and brain functional abnormalities in patients with mild Alzheimer's Disease (AD) and patients with amnesic Mild Cognitive Impairment (aMCI). METHODS: we used resting spect-neuropsychology correlations method. RESULTS: We found that parieto-temporal associative cortex, mainly involving the inferior parietal lobule, posterior cingulate and middle temporal gyrus, is compromised early in AD. These results suggest that the dysfunction in these areas contributes to cognitive decline in the storage of verbal information, drawing abilities and non-verbal abstract reasoning in AD. The aMCI group showed hypoperfusion primarily involving the frontal areas bilaterally, and this correlated with the impairment in free delayed recall on a verbal memory task. CONCLUSION: Our results underlie the clinical differences between AD and aMCI patients that might reflect the involvement of different degenerative mechanisms in these groups.

Dopamine agonists can improve pure apathy associated with lesions of the prefrontal-basal ganglia functional system.

Apathy is a common neurobehavioral symptom of other syndromes or a syndrome per se which occurs in a variety of neuropsychiatric disorders. Apathy depends on disruption of emotional, cognitive, and behavioral functions. Six brain-damaged patients were assessed, including five patients with unilateral or bilateral focal lesions of the basal ganglia or the thalamus (showing apathy due to an auto-activation deficit) and one patient with bilateral lesions in the limbic temporomesial cortex associated with a form of emotional-affective apathy. A significant and persistent improvement of apathy was observed in all patients after treatment with dopamine agonists such as pramipexole, ropinirole, and rotigotine. These results confirm preliminary reports on the beneficial effects of dopamine agonist agents on apathy and suggest that this syndrome can be treatable in many cases.

Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

Gastrointestinal involvement is a well known complication of Ehlers-Danlos syndromes (EDSs), mainly in form of abdominal emergencies due to intestinal/abdominal vessels rupture in vascular EDS. In the last decade, a growing number of works investigated the relationship between a wide spectrum of chronic gastrointestinal complaints and various EDS forms, among which the hypermobility type (a.k.a. joint hypermobility syndrome; JHS/EDS-HT) was the most studied. The emerging findings depict a major role for gastrointestinal involvement in the health status and, consequently, management of JHS/EDS-HT patients. Nevertheless, fragmentation of knowledge limits its impact on practice within the boundaries of highly specialized clinics. In this paper, literature review on gastrointestinal manifestations in JHS/EDS-HT was carried out and identified papers categorized as (i) case-control/cohort studies associating (apparently non-syndromic) joint hypermobility and gastrointestinal involvement, (ii) case-control/cohort studies associating JHS/EDS-HT and gastrointestinal involvement, (iii) case reports/series on various gastrointestinal complications in (presumed) JHS/EDS-HT, and (iv) studies reporting gastrointestinal features in heterogeneous EDS patients' cohorts. Gastrointestinal manifestations of JHS/EDS-HT were organized and discussed in two categories, including structural anomalies (i.e., abdominal/diaphragmatic hernias, internal organ/pelvic prolapses, intestinal intussusceptions) and functional features (i.e., dysphagia, gastro-esophageal reflux, dyspepsia, recurrent abdominal pain, constipation/diarrhea), with emphasis on practice and future implications. In the second part of this paper, a summary of possible nutritional interventions in JHS/EDS-HT was presented. Supplementation strategies were borrowed from data available for general population with minor modifications in the light of recent discoveries in the pathogenesis of selected JHS/EDS-HT features.

Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping connective tissue disorders characterized by chronic/recurrent pain, joint instability complications, and minor skin changes. Fatigue and headache are also common, although are not yet considered diagnostic criteria. JHS/EDS-HT is a unexpectedly common condition that remains underdiagnosed by most clinicians and pain specialists. This results in interventions limited to symptomatic and non-satisfactory treatments, lacking reasonable pathophysiologic rationale. In this manuscript the fragmented knowledge on pain, fatigue, and headache in JHS/EDS is presented with review of the available published information and a description of the clinical course by symptoms, on the basis of authors' experience. Pathogenic mechanisms are suggested through comparisons with other functional somatic syndromes (e.g., chronic fatigue syndrome, fibromyalgia, and functional gastrointestinal disorders). The re-writing of the natural history of JHS/EDS-HT is aimed to raise awareness among clinical geneticists and specialists treating chronic pain conditions about pain and other complications of JHS/EDS-HT. Symptoms' clustering by disease stage is proposed to investigate both the molecular causes and the symptoms management of JHS/EDS-HT in future studies.

Using the Rey Auditory Verbal Learning Test (RAVLT) to differentiate alzheimer's dementia and behavioural variant fronto-temporal dementia.

In patients with focal lesions, patterns of learning, retrieval, and recognition deficits vary according to site of damage. Because different brain regions are affected by the underlying pathology in Alzheimer's dementia (AD) and behavioral variant fronto-temporal dementia (bvFTD), one might predict that the two disorders would result in different sorts of memory deficits on the Rey Auditory Verbal Learning Test (RAVLT). The aim of this investigation was to find a way to differentiate AD, bvFTD, and normal controls (NC) reliably based on RAVLT scores from retrospective samples of 82 Italian and 43 Australian participants. Results indicated that the groups differed on measures of learning, retroactive interference, delayed recall, and delayed recognition. Although delayed recall distinguished participants in the three groups across both samples, no one set of cut-offs could be obtained with adequate sensitivity and specificity. However, when we created a combined score (the "RAVLT Memory Efficiency Index": {[(delayed recall A/15)/(RAVLT Trials 1-5/75)] + [(delayed recognition hits/15) - (false positive/total number of distractors)]}), we were able to find cut-offs that differentiated the groups with good sensitivity and specificity across variations in RAVLT methodology, participant samples, and languages. This index will increase the usefulness of the RAVLT in differential diagnoses of early dementia.

Anosognosia in mild cognitive impairment and mild Alzheimer's disease: frequency and neuropsychological correlates.

OBJECTIVES: To evaluate severity of anosognosia and to identify its neuropsychological correlates in preclinical and clinical Alzheimer's Disease (AD). METHODS: The Clinical Insight Rating Scale, the Anosognosia Questionnaire for Dementia (AQ-D), and the Mental Deterioration Battery were used to assess anosognosia and cognitive performances in mild AD (N = 38), amnesic mild cognitive impairment (a-MCI; N = 35), and multiple domain MCI (md-MCI; N = 38). RESULTS: Patients with mild AD were more anosognosic than both MCI groups, which, however, did not differ from one other. A categorical diagnosis of anosognosia was made in 42% of patients with mild AD, 3% of md-MCI, but in no subjects with a-MCI. Reduced verbal episodic memory raw score was associated with decreased awareness of cognitive difficulties (AQ-D total and intellectual functioning scores) only in MCI. In mild AD, anosognosia was linked only to increased age and reduced basic activities of daily living performances. CONCLUSIONS: The diagnosis of anosognosia is frequent in patients with mild AD but not in those with MCI. In the latter case, the authors cannot speak of true anosognosia but only of decreased awareness of illness. Furthermore, reduced awareness of cognitive difficulties is linked with verbal memory performances in patients with MCI but not in those with AD, suggesting for the latter the involvement of factors other than neuropsychological. Thus, neuropsychiatric dimensions commonly present in patients with AD should be investigated along with anosognosia.

Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer's disease and mild cognitive impairment subtypes.

BACKGROUND: Neuropsychiatric disorders are common in cognitively impaired older persons, and associated with institutionalization and caregiver stress in Alzheimer's disease (AD). Few studies have compared the occurrence of both psychiatric disorders and neuropsychiatric symptoms in patients with AD and mild cognitive impairment (MCI) subtypes. We aimed to investigate the frequency of psychiatric disorders and neuropsychiatric symptoms in AD and MCI patients, compared to controls. METHODS: We included 245 outpatients of a memory clinic in Rome, Italy (119 AD; 68 multidomain-MCI; 58 amnestic-MCI) and 107 controls. Categorical disorders of depression and apathy were diagnosed with structured interviews. Symptoms were evaluated with the Neuropsychiatric Inventory (NPI). The odds ratios (OR) of patients having neuropsychiatric symptoms compared to controls were calculated with logistic regression, adjusted for sociodemographic and clinical variables. RESULTS: A large proportion of AD (49.6%) and multidomain-MCI (44.1%) patients had depression disorder. Apathy disorder was common in AD (51.3%) but less frequent in amnestic-MCI (6.9%) and multidomain-MCI (14.7%). AD patients were three times more likely to have depression disorders (OR = 3.0, CI = 1.1-7.6) or apathy (OR = 16.9, CI = 4.6-61.8) compared to amnestic-MCI, and seven times more likely to have apathy disorder than multidomain-MCI (OR = 7.5, CI = 3.0-19.2). After apathy and depression, the most prevalent neuropsychiatric symptoms in AD and MCI were anxiety, agitation, irritability, night-time behaviors, and appetite disturbances. There was an increasing prevalence of many neuropsychiatric symptoms with increasing severity of cognitive syndromes. CONCLUSIONS: Clinicians should consider the relevance of neuropsychiatric disorders and symptoms in patients with cognitive disturbances, and incorporate a thorough psychiatric examination in the evaluation of patients.

Clinical findings, functional abilities and caregiver distress in the early stage of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).

Few studies have compared neuropsychiatric disorders and functional abilities in the early stage of DLB and AD and their influence on caregiver distress. The aim of this study is to assess neuropsychiatric disorders, functional abilities and caregiver distress in DLB and in AD subjects. Sixteen subjects affected by probable DLB and 12 subjects affected by probable AD were enrolled. All subjects underwent a wide neuropsychological examination. Caregiver's distress was also assessed. Subjects affected by DLB performed better in long-term memory tests, whereas AD subjects performed better in attentive and executive function tests. The Neuropsychiatric Inventory (NPI) total score was significantly higher in DLB subjects than in AD subjects. Furthermore, DLB subjects scored worse than AD subjects in both Activities of Daily Living scale (ADL) and Instrumental Activities of Daily Living scale (IADL) scales. Overall caregiver distress was higher in DLB than in AD subjects. High distress was observed in DLB caregivers alone and was caused by delusion, hallucinations, anxiety and apathy. DLB subjects have a different neuropsychological profile, more psychiatric symptoms and more serious functional deficits than AD subjects in the early cognitive decline, furthermore DLB caregivers are more stressed than AD caregivers.

Category-specific knowledge deficit for animals in a patient with herpes simplex encephalitis.

A large number of brain-damaged patients with heterogeneous category-specific deficits have been reported in literature. This has given rise to different theories concerning the processing of semantic knowledge. In this paper we report the case of K.C. who, after a bout of herpes simplex encephalitis, displayed a category-specific impairment restricted to the knowledge of animals, irrespective of input modality. K.C.'s magnetic resonance imaging (MRI) showed multiple bilateral antero-mesial and inferior temporal lesions. Although she was impaired for both the perceptual (visual and auditory) and functional/associative attributes of animals, she performed normally in an object-reality decision task involving pictures of animals and nonanimals. The dissociation between K.C.'s intact structural description system and her impaired semantic knowledge is interpreted according to hierarchical interactive theory (HIT), which assumes that conceptual knowledge is hierarchically organized in separate but interactive multiple knowledge substores. K.C.'s results indicate that her access to a presemantic structural description system was intact so that her impairment on animal semantic knowledge arose later at a conceptual stage of the object recognition system. Furthermore, K.C.'s deficits indicate selective disruption of a special class of animate concepts within the broad category of living things, which seems best explained by the "domain-specific knowledge theory" proposed by Caramazza and Shelton.