Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies.

OBJECTIVE: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. METHODS: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. RESULTS: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. CONCLUSIONS: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

High specificity of MMSE pentagon scoring for diagnosis of prodromal dementia with Lewy bodies.

BACKGROUND: Patients with dementia with Lewy bodies (DLB) may display a different cognitive pattern from Alzheimer's disease (AD) with more severe impairment performing visuospatial/visuoconstructive tasks. The aim of this study was to investigate whether the analysis of the MMSE pentagon copy could be a useful diagnostic screening tool in prodromal DLB. METHODS: Fifty-three patients with Mild Cognitive Impairment (MCI) were followed over 3-years until a diagnosis of DLB (MCI-DLB: n = 30) and AD (MCI-AD: n = 23) were made according to standard criteria. At the first assessment patients underwent a thorough cognitive assessment including the Qualitative Scoring MMSE Pentagon Test (QSPT), the NPI, the UPDRS as well as questionnaires to determine fluctuations and sleep disorders. RESULTS: The percentage of subjects who were unable to determine the correct number of angles in the pentagon copy test was 45.1% of MCI-DLB and 8.3% of MCI-AD patients (sensitivity 41.1%; specificity 91%). Attentive/executive functions and visual-spatial abilities were worse in the MCI-DLB group, while episodic memory impairment was greater in MCI-AD. Subtle extrapyramidal signs (63%) and RBD symptoms (56%) were the most frequent clinical features supporting the diagnosis of MCI-DLB. CONCLUSIONS: We suggest that a poor performance in determining the number of angles when performing the pentagon copying test, together with the presence of subtle extrapyramidal signs and symptoms of RBD may serve as a predictive tool for early DLB.

Feasibility and efficacy of cognitive telerehabilitation in early Alzheimer's disease: a pilot study.

BACKGROUND: This pilot study compared the effects of lexical-semantic stimulation through telecommunication technology (LSS-tele) with in-person LSS (LSS-direct) and unstructured cognitive treatment (UCS) in patients with early Alzheimer's disease. METHODS: Twenty-seven patients with Alzheimer's disease in the very early stage (Mini-Mental State Examination [MMSE] >26/30) were divided into three groups: seven patients received LSS-tele treatment, ten received standard LSS-direct intervention, and ten participants underwent UCS as control condition. Intervention treatments consisted of two weekly sessions of LSS (through teleconference or face to face depending on group assignment) or UCS exercises administered to small groups throughout a 3-month period. The main outcome measures were changes of global cognitive performance, language abilities, and memory function. Secondary outcome measures were changes in attention, working memory, executive functions, and visual-spatial abilities tests. RESULTS: The mean MMSE score improved significantly in LSS-tele and LSS-direct treatments; LSS-tele improved language abilities, both phonemic and semantic, and stabilized delayed verbal episodic memory with respect to an improved performance after the LSS-direct intervention and to a memory decline observed in the control group. Improvement was not achieved in any neuropsychological test score after UCS. CONCLUSION: Clinical application of telecommunication technology to cognitive rehabilitation of elderly patients with neurodegenerative cognitive impairment is feasible and may improve global cognitive performance. Technical aspects to ameliorate efficacy of delivery may further improve its impact on domain-specific cognitive abilities.

Impulse control disorders in frontotemporal dementia: spectrum of symptoms and response to treatment.

OBJECTIVE: To describe a patient with behavioral variant frontotemporal dementia (bvFTD) presenting with impulse control disorders (ICDs) which responded to fluvoxamine and topiramate. CASE REPORT: A 64-year-old woman was affected by several ICDs. At disease onset, she suffered from impulsive smoking and overeating which caused a body weight increase of 20 kg in 6 months. Later on she manifested binge-eating behavior and skin-picking compulsion. Presence of progressive frontal cognitive impairment (Mini Mental State Examination 24/30) and evidence of hypoperfusion of the anterior cingulate and dorsolateral frontal cortex with brain single-photon emission computed tomography scan contributed to the diagnosis of bvFTD. Use of combination treatment with selective serotonin reuptake inhibitor drugs and topiramate improved all these symptoms. CONCLUSION: This case extends the clinical phenotype of repetitive and compulsive habits in bvFTD to encompass symptoms suggestive of ICDs. It is proposed that fluvoxamine and topiramate may be considered as treatment options in these conditions.

Case series evidence for improvement of executive functions after late cranioplasty.

OBJECTIVE: Craniectomy, used to relieve refractory intracranial pressure in traumatic brain injury (TBI), may cause cognitive deficits which could be improved by skull breach repair. This paper studied whether late cranioplasty improves a specific pattern of cognitive functions. DESIGN: A case series of five TBI patients with craniectomy undergoing late cranioplasty (median interval time: 14 months, range: 12-36). METHODS: Longitudinal neuropsychological and brain MRI assessments 1 week before cranioplasty and 3 months later. RESULTS: After cranioplasty, mean score of the verbal fluency test improved compared to pre-cranioplasty (p = 0.02). Similarly, significant improvements after cranioplasty were observed in other tests scores exploring executive functions, such as working memory (p = 0.03) and speed of attention (p = 0.04), independently from the size and site of cranioplasty. CONCLUSIONS: The cognitive improvement induced by cranioplasty, even when performed after a long interval from craniectomy, may be due to the restoration of physiological cerebrospinal fluid circulation which, in turn, allows an efficient brain volume transmission signal circulation. The restoration of this essential way of signal communication seems to affect large-scale neuronal networks responsible for the executive functions.

Combined duloxetine and benzodiazepine-induced visual hallucinations in prodromal dementia with Lewy bodies.

OBJECTIVE: We describe a patient with prodromal dementia with Lewy bodies (DLB) presenting with drug-induced visual hallucinations (VHs). CASE REPORT: A 78-year-old woman complained of daytime recurrent VHs characterized by seeing her face and arms covered in fur and viewing moustaches on her daughter's face. VHs started a few days after the beginning of a combination therapy with duloxetine and lorazepam and ceased within 24 h after their discontinuation. Nonamnestic mild cognitive impairment with profound visual perception deficits and very mild extrapyramidal signs, with abnormal brain DaTscan single photon emission tomography, were present. Three years later, cognitive and neurological follow-up assessments supported the diagnosis of DLB. CONCLUSION: Perturbation of cerebral serotonergic tone induced by duloxetine, associated with reduced attentional control due to benzodiazepine use, may be the physiopathological substrate of transient VHs in prodromal DLB.

Clinical and cognitive correlates of visual hallucinations in dementia with Lewy bodies.

BACKGROUND: The presence of recurrent complex visual hallucinations (VHs) is a core feature of dementia with Lewy bodies (DLB). The aim of this study was to investigate which clinical and neuropsychological characteristics are associated with VHs and their predictive value over a 1 year follow-up. METHODS: 81 DLB patients, 41 with (VH+) and 36 without (VH-) VHs, and 45 patients with Alzheimer's disease (AD), were enrolled. All participants underwent extensive neuropsychological testing. Visual-spatial and perceptual abilities were evaluated with the Visual and Object Space Perception (VOSP) battery. Fluctuations in attention, rapid eye movement sleep behaviour disorder (RBD) symptoms, extrapyramidal signs and behavioural disturbances were studied with dedicated clinical scales. RESULTS: The presence of VHs was associated with older age and later disease onset, but not with disease duration or with fluctuations, RBD or parkinsonism severity. Cognitive correlates of VHs were deficits in visual attention (digit cancellation: p<0.005) and executive functions (clock drawing: p<0.05; digit span forward: p<0.05) on a background of a slightly worse global cognitive performance (Mini-Mental State Examination: p=0.05). Visual-perceptual and visual-spatial deficits were significantly worse in DLB than in AD patients (VOSP subtests scores 1, 6, 7 and 8) but were not different in DLB VH+ and VH-, except for subtest 6. Poor performance in the visual attention task was an independent predictor of VHs. DISCUSSION: Impairment of visual-spatial and perceptual abilities in DLB represents a disease related cognitive signature, independent of the presence of VHs, for which it may represent a predisposing condition. Visual attention, instead, is the main cognitive determinant for the genesis of VHs.

Effects of lexical-semantic treatment on memory in early Alzheimer disease: an observer-blinded randomized controlled trial.

BACKGROUND: Episodic memory and semantic abilities deteriorate early in Alzheimer disease (AD). Since the cognitive system includes interconnected and reciprocally influenced neuronal networks, the authors hypothesized that stimulation of lexical-semantic abilities may benefit semantically structured episodic memory. OBJECTIVE: To investigate the effects of lexical-semantic stimulation (LSS) on verbal communication and episodic memory in early AD. METHODS: Forty AD participants were randomized to LSS or unstructured cognitive stimulation (UCS) as control condition. Treatments lasted 3 months, 2 sections a week. The primary outcome measures were the Mini-Mental State Examination (MMSE), Boston Naming Test (BNT), Verbal Naming Test (VNT), Phonemic and Semantic Fluency, Story Recall, and Rey Auditory Verbal Learning (RAVL). Secondary outcome measures were neuropsychological tests assessing cognitive functions not stimulated by the intervention, such as attention, executive functions, and visual-spatial abilities, and the instrumental activities of daily living scale. A 6-month follow-up assessment was administered to the LSS group. RESULTS: LSS treatment yielded significant improvements of the MMSE, BNT, VNT, Brief Story Recall, and RAVL delayed recall mean scores. Among secondary outcome measures, only working memory and the speed of a task assessing executive functions (Stroop test) improved after LSS. Unstructured cognitive stimulation intervention did not improve any cognitive domain. Six months after LSS discontinuation, the MMSE mean score remains significantly higher than the baseline value. CONCLUSION: LSS treatment may improve episodic memory in AD patients and may be regarded as a clinical option to counteract the cognitive decline typical of the disease.