Cognitive disorders in migrants: retrospective analysis in a Center for Cognitive Disorders and Dementia in Milan.

BACKGROUND: The number of migrants with dementia in Italy might increase considerably over the coming years due to the increasing flow of immigration and the aging of the population. AIMS: We retrospectively registered rate and characteristics of demented migrant outpatients referred to one hospital in Milan from 2001 to 2017. METHODS: Information about country of origin of migrants attending general neurology and memory clinics was obtained from their Italian tax code. Socio-demographic, cultural, and clinical characteristics were derived from their medical records. RESULTS: Migrants with cognitive decline represented a minimal fraction (3.1%) of demented outpatients, but a grow rate of 400% was registered within the period of observation. A linguistic barrier resulted as the main obstacle for the application of available diagnostic tools for dementia. DISCUSSION/CONCLUSION: Given the above-reported data, the implementation of strategies (such as transcultural diagnostic instruments) and policies dedicated to this growing health problem appears a priority for our health systems.

Estimating dementia cases amongst migrants living in Europe.

BACKGROUND AND PURPOSE: The phenomenon of dementia amongst migrants and ethnic minorities represents an emerging concern for European healthcare systems, posing additional challenges in terms of clinical approach, access to care and resource utilization. The aim of the present study was to estimate the cases of dementia amongst immigrant older subjects living in Europe and in each European country. METHODS: The estimated cases of dementia amongst older (i.e. 65+) migrants living in the European Union (EU-28) and European Free Trade Association member states were calculated by multiplying the number of migrants (obtained through the data provided by Eurostat) with the age- and sex-specific prevalence rates (derived by a recent meta-analysis). RESULTS: Overall, 6 507 360 older migrants lived in Europe in 2017. In addition, 1 204 671 migrants were registered in Germany in 2010. Nearly 475 000 dementia cases (329 028 women, 147 410 men) were estimated in this population by applying age- and sex-specific prevalence rates. When considering each European country, the number of estimated cases ranged from 108 (Iceland) to 119 161 (France). In parallel, the proportion of dementia cases occurring in migrants ranged from 0.9% (Czech Republic) to 51.2% (Liechtenstein). CONCLUSIONS: The issue of dementia in migrants and ethnic minorities is emerging but already relevant for European healthcare systems. The magnitude of this phenomenon and its complexities reinforce the need for coordinated initiatives both at a national and continental level. These epidemiological data should ideally be integrated with those coming from 'real world' services in order to better calibrate these actions.

Resolution of unilateral upper limb action tremor after surgical treatment of a contralateral frontoparietal arachnoid cyst.

PURPOSE: Arachnoid cysts (ACs) are cerebrospinal fluid-filled sacs. Although ACs are a frequent finding on neuroimaging, most remain asymptomatic during lifetime. CASE REPORT: We report a very rare case of a 62-year-old female patient presenting with a tremor due to a giant arachnoid cyst, which completely resolved after cyst-peritoneal shunting.

What are the caregivers' needs on dementia care? An integrated qualitative and quantitative assessment.

Dementia is one of the main causes of disability later in life. Interventions in support of patients with dementia aim at granting the highest level of independence in activities of daily living and at delivering the required facilities; formal and informal caregivers represent the interface between patients and health services. The aims of our study were to assess caregivers' perceived needs and to relate them to their own socio-cultural features and to patients' clinical characteristics. During three consecutive months, 50 caregivers of patients with dementia were interviewed about their needs in the assistance of subjects with dementia by means of three structured questionnaires (Caregiver Needs Assessment [CNA], Zarit Burden Inventory [ZBI], Neuropsychiatric Inventory-Questionnaire [NPI-Q]) and of two open-ended questions. Higher scores of CNA (suggestive of more needs) were associated with a major burden in caregiving and were related to a more severe behavioral and psychological profile of patients with dementia. ZBI was highly correlated with NPI distress score. Among caregivers, the children of patients reported more needs, particularly about information on disease and how to cope with it. CNA emerged as a complete and reliable instrument, with need for safety being the only item missing from the questionnaire and identified by means of the open-ended questions. Our results showed how the use of simple and brief instruments can increase the communication between health operators and caregivers and could thus improve the quality of formal and informal assistance.

Use of benzodiazepines and cognitive performance in primary care patients with first cognitive complaints.

ABSTRACTThe aim of the present study is to investigate the impact of benzodiazepine use on cognitive performance in primary care patients with first cognitive complaints. The association between the exposition to benzodiazepines (short and long half-life) and cognitive performance, evaluated through the Mini Mental State Examination (MMSE), was tested through analysis of the covariance and logistic regression models. Within the 4,249 participants (mean age 77.0 ± 8.2, 66.4% women), 732 (17%) were on benzodiazepines. When compared with non-users, short- and long-acting benzodiazepine users presented overlapping adjusted MMSE mean scores (respectively, mean MMSE score: 25.3, 95%CI 25.2-25.5; 25.4, 95%CI 25.1-25.7, and 25.9, 95%CI 25.3-26.4; p = 0.156). When tested according to the logistical regression model, after adjusting for potential confounders, no association was found between short and long acting benzodiazepine use and a MMSE < 24 (respectively, OR 0.9, 95%CI 0.7-1.2; OR 0.8, 95%CI 0.7-1.3) as compared with non-users. In conclusion, according to the results of our study, benzodiazepine use seems not to impact on cognitive performance- as assessed with the MMSE- of primary care patients referring to GPs for first cognitive complaints.

Role of anticholinergic burden in primary care patients with first cognitive complaints.

BACKGROUND AND PURPOSE: Drugs with anticholinergic properties might have a negative impact on cognition, but findings are still conflicting. The association was evaluated between anticholinergic drugs and cognitive performance in primary care patients with first cognitive complaints. METHODS: From April 2013 to March 2014, 353 general practitioners administered the Mini-Mental State Examination (MMSE) to patients presenting with first cognitive complaints. Drug history was collected and the anticholinergic cognitive burden (ACB) was scored and categorized as ACB 0, ACB 1 and ACB 2+. A mixed effect linear regression model was used to assess the association between ACB and MMSE score. RESULTS: Of 4249 subjects entering the study (mean age 77 ± 8.2 years, 66.4% women and mean years of schooling 8.9 ± 4.5), 25.8% received at least one drug with anticholinergic action. According to multivariate analysis, and after adjustment for several confounders, subjects with ACB 2+ had a statistically significant lower MMSE score compared with those with ACB 0 (ß -0.63; 95% confidence interval -1.19; -0.07). Subjects with ACB 1 had a non-statistically significant lower MMSE score than those with ACB 0 (ß -0.11; 95% confidence interval -0.37; 0.15). CONCLUSIONS: Anticholinergic medication might affect cognitive function in people with first cognitive complaints. Alternatives should be taken into account when possible, balancing the benefits and harms of these medications.

Adaptation and psychometric properties of the Italian version of the Non-Motor Symptoms Questionnaire for Parkinson's disease.

Although non-motor symptoms (NMS) of Parkinson's disease (PD) are very common also in early stages of the disease, they are still under-recognized. Screening tools for non-motor symptoms, such as non-motor symptoms questionnaire (NMSQuest), help clinicians to recognize NMS and to evaluate if patients could require further assessment or specific treatments. To validate an adapted Italian version of NMSQuest and study its psychometric properties, Italian PD patients self-completed Italian NMSQuest, and then underwent a standard clinical evaluation including motor assessment (by Hoehn and Yahr staging, unified Parkinson's disease rating scale part III) and non-motor assessment (by Montreal cognitive assessment, Beck depression inventory, neuropsychiatric inventory, Epworth sleepiness scale, scale for outcomes in Parkinson's disease-Autonomic and movement disorder society-sponsored revision of the unified Parkinson's disease rating scale part I). Somatic comorbidities were quantified using the modified cumulative illness rating scale (CIRS). Seventy-one subjects were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean duration of disease 6.3 ± 4.6 years; H&Y median 2). Italian NMSQuest showed adequate satisfactory clinimetrics in terms of data quality, precision, acceptability, internal consistency and reliability. A significant correlation was found between NMSQuest and most of non-motor assessment scales, while no significant correlation appeared with motor severity as well as with age of patients, disease duration, levodopa equivalent daily dose, L-DOPA/dopamine agonists assumption and CIRS total score. The Italian version of the NMSQuest resulted as a reliable instrument for screening NMS in Italian PD patients.

The Luigi Sacco Hospital VAS-COG stroke care pathway: A five-year experience.

Background: Psycho-cognitive consequences are a frequent cause of disability in stroke survivors but are often underdiagnosed also because of lack of services dedicated to these aspects. We started assessing systematically cognitive and behavioral functions in acute stroke patients and to follow them up. Here, we report a retrospective analysis of the organization of the Sacco VAS-COG stroke care pathway and the refinements implemented during 5 years of activity. Methods: The protocol includes baseline collection of clinical history, general and neurologic examinations, functional, neuropsychological, and neuroimaging assessment. At follow-up, a diagnosis of cognitive decline was made based on best clinical judgment in the first period (January 2018 to May 2019, namely VAS-COG protocol 1.0) and then based on an extensive neuropsychological battery (May 2019 to January 2023, namely VASCOG protocol 2.0); psychiatric and behavioral disturbances are investigated through suitable scales. Results: From January 2018 to December 2022, 834 patients (mean age 76±13.6 years; 46.6 % females) with acute cerebrovascular events were admitted to the stroke unit, mostly (80 %) for ischemic strokes. Pre-event cognitive impairment was not assessable in 78 patients (9.3 %) because no reliable informant was present and was reported in 327/756 (43 %) patients. During follow-up, post-stroke cognitive impairment was detected in 124/217 (57.1 %) patients in VAS-COG protocol 1.0 and in 137/201(68.2 %) patients in VAS-COG protocol 2.0, while 95/218 (43.2 %) patients were found to be depressed and patients presented on average 2.5 neuropsychiatric symptoms on Neuropsychiatric Inventory-questionnaire. Conclusions: The VAS-COG stroke care pathway represents a model for patients and for their families.

Free and Cued Selective Reminding Test: an Italian normative study.

The presence of episodic memory impairment is required for the diagnosis of Alzheimer's dementia by all current diagnostic criteria. The new research criteria proposed by Dubois et al. (Lancet Neurol 6:734-746, 2007) require that the impairment should not improve significantly with cueing, recognition testing nor after the control of effective encoding. This is considered to be the core deficit of "prodromal Alzheimer's disease". The Free and Cued Selective Reminding Test (FCSRT) is a memory test that allows in assessing these specific features of memory impairment. Here, we report normative data for an Italian version of the FCSRT. The test is based on the 12 pictorial stimuli, 6 belonging to the living domain, and 6 to the non-living domain. Six scores were derived from the performance of 227 healthy Italian adults, with age, sex and education homogenously distributed across subgroups: immediate free recall (IFR), immediate total recall (ITR), delayed-free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. In multiple regression analyses, age emerged as an influencing factor for both IFR and DFR, with older people obtaining lower scores. Education and gender appear to influence only IFR, with better performance by more educated subjects and females. Adjusted scores were used to determine inferential cutoff scores and to compute equivalent scores.

Exploring cocoa properties: is theobromine a cognitive modulator?

Nutritional qualities of cocoa have been acknowledged by several authors; a particular focus has been placed on its high content of flavanols, known for their excellent antioxidant properties and subsequent protective effect on cardio- and cerebrovascular systems as well as for neuromodulatory and neuroprotective actions. Other active components of cocoa are methylxanthines (caffeine and theobromine). Whereas the effects of caffeine are extensively researched, the same is not the case for theobromine; this review summarizes evidence on the effect of theobromine on cognitive functions. Considering animal studies, it can be asserted that acute exposition to theobromine has a reduced and delayed nootropic effect with respect to caffeine, whereas both animal and human studies suggested a potential neuroprotective action of long-term assumption of theobromine through a reduction of Aß amyloid pathology, which is commonly observed in Alzheimer's disease patients' brains. Hence, the conceivable action of theobromine alone and associated with caffeine or other cocoa constituents on cognitive modulation is yet underexplored and future studies are needed to shed light on this promising molecule.

Novel exon 1 progranulin gene variant in Alzheimer's disease.

BACKGROUND AND PURPOSE: Progranulin (PGRN) expression is increased in activated microglia in Alzheimer's disease (AD) brain, suggesting a potential role in this pathology. METHODS: A mutation scanning of exons and flanking regions of PGRN was carried out in 120 patients with sporadic frontotemporal lobar degeneration and 145 with sporadic AD. RESULTS: Amongst variants not yet deposited, a novel allelic variant was identified in Exon 1 (g100169G > A). It leads to an amino acidic change (p.Gly35Arg) and was observed in a patient with late onset AD. In silico analysis predicted that this mutation is possibly damaging. A second variant (g.100165C > T), resulting in a silent mutation (pAsp33Asp), was found in a patient with semantic dementia and in another with early onset AD. Both variants were absent in 226 controls. In addition, two rare non-pathogenic variants lying very close to PGRN splice-site regions (IVS2 + 7-->G > A and IVS7 + 7-->G > A) were observed. Transcriptional analysis in peripheral blood mononuclear cells from patients demonstrated they do not affect exon splicing. CONCLUSIONS: A novel putative PGRN mutation leading to an amino acidic substitution was identified in a patient with clinical AD.

Intercepting Parkinson disease non-motor subtypes: A proof-of-principle study in a clinical setting.

The construct of non-motor symptoms (NMS) subtyping in Parkinson Disease (PD) is emerging as a line of research in the light of its potential role in etiopathological interpretation of PD heterogeneity. Different approaches of NMS subtyping have been proposed: an anatomical model suggests that NMS aggregate according to the underpinning pathology; other researchers find aggregation of NMS according to the motor phenotype; the contribution of genetic background to NMS has also been assessed, primarily focusing on cognitive impairment. We have analyzed NMS burden assessed through an extensive clinical and neuropsychological battery in 137 consecutive non-demented PD patients genotyped for MAPT haplotypes (H1/H1 vs H2 carriers) in order to explore the applicability of the "anatomo-clinical", "motor" or "genetic" models for subtyping PD in a clinical setting; a subsequent independent analysis was conducted to verify a possible cluster distribution of NMS. No clear-cut NMS profiles according to the previously described models emerged: in our population, the autonomic dysfunctions and depressive symptoms represent the leading determinant of NMS clusters, which seems to better fit with the hypothesis of a "neurotransmitter-based" model. Selective preferential neurotransmitter network dysfunctions may account for heterogeneity of PD and could address translational research.

Validation of the Italian version of the Non Motor Symptoms Scale for Parkinson's disease.

OBJECTIVE: To validate the adapted Italian version of the Non-Motor Symptoms Scale (NMSS), a tool to assess non-motor symptoms (NMS) in Parkinson's disease (PD). METHODS: A cross cultural adaptation of the NMSS into Italian and a psychometric analysis of the translated version of the NMSS was carried out in patients with PD from two university centres-affiliated hospitals. The quality of data and the acceptability, reliability and construct validity of NMSS were analyzed. The following standard scales were also applied: Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale (UPDRS) part III, Montreal Cognitive Assessment, Beck Depression Inventory, Neuropsychiatric Inventory, Epworth Sleepiness Scale, Autonomic Scale for Outcomes in Parkinson's disease-Motor, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part I and Modified Cumulative Illness Rating Scale (CIRS). Levodopa equivalent daily dose (LEDD) was calculated. RESULTS: Seventy-one patients with PD were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean length of disease 6.3 ± 4.6 years; H&Y median: 2). Mean NMSS was 39.76 (SD 31.9; skewness 0.95). The total score of NMSS was free of floor or ceiling effects and showed a satisfactory reliability (Cronbach's alpha coefficient on total score was 0.72 [range for domains: 0.64-0.73], SEM value was 3.88 [½ SD = 31.90]). Significant positive correlations were found among total NMSS and other NMS standard tests, but no significant correlation appeared with UPDRS part III, CIRS and LEDD. CONCLUSIONS: The Italian NMSS is a comprehensive and helpful measure for NMS in native Italian patients with PD.

Clinical presentation and outcome of Guillain-Barré and related syndromes in relation to anti-ganglioside antibodies.

We correlated the clinical features of 78 patients with Guillain-Barré syndrome (GBS) or related variants, with the presence of serum antibodies to the gangliosides GM1, GM2, GD1a, GD1b and GQ1b in order to determine whether these antibodies may influence the clinical presentation or outcome of GBS. Sixty-three patients had typical GBS (81%), nine a pure motor form (11%), three a paraparetic form (4%), and three had Miller Fisher syndrome (MFS). IgG or IgM (or both) anti-ganglioside antibodies were found by ELISA in 37% of patients, including 36% with typical, 33% with pure motor and 100% with MFS. Beside the constant occurrence of anti-GQ1b antibodies in patients with MFS (P<0.00001), the other clinical forms were not associated with a specific anti-ganglioside reactivity. Anti-GM1 and anti-GD1a antibodies tended to be associated with a worse disability at 6 month than other or no reactivity and, similarly to anti-GM2 antibodies, with a more frequent respiratory impairment. Anti-GM2 and anti-GD1b antibodies were always associated with typical GBS and, in all but one patient, with a complete recovery; still they were found in only 13 and 3%, respectively, of the patients with this presentation. Anti-GQ1b antibodies, though always associated with ophthalmoplegia and ataxia in both MFS and GBS, were found in only 36 and 26%, respectively, of patients with these symptoms. Even if different anti-ganglioside antibodies tend to be associated with some clinical features possibly suggesting that they may influence the clinical presentation or outcome, with the exception of anti-GQ1b antibodies for ophthalmoplegia and ataxia, they do not permit to predict the clinical presentation or outcome in individual patients.

Selective uppercase dysgraphia with loss of visual imagery of letter forms: a window on the organization of graphomotor patterns.

We report a patient who, after a left parieto-occipital lesion, showed alexia and selective dysgraphia for uppercase letters. He showed preserved oral spelling, associated with handwriting impairment in all written production; spontaneous writing, writing to dictation, real words, pseudowords, and single letters were affected. The great majority of errors were well-formed letter substitutions: most of them were located on the first position of each word, which the patient always wrote in uppercase (as he used to do before his illness). The patient also showed a complete inability to access the visual representation of letters. As demonstrated by a stroke segmentation analysis, letter substitutions followed a rule of graphomotor similarity. We propose that the patient's impairment was at the stage where selection of the specific graphomotor pattern for each letter is made and that the apparent selective disruption of capital case was due to a greater stroke similarity among letters belonging to the same case. We conclude that a visual format is necessary neither for spelling nor for handwriting.

Differences in hippocampal metabolism between amnestic and non-amnestic MCI subjects: automated FDG-PET image analysis.

AIM: The aim of this study was to assess whether 18F-fluorodeoxyglucose positron emission tomography differentiates amnestic (aMCI) from single-non-amnestic mild cognitive impairment (snaMCI) with executive dysfunction. METHODS: Sixteen aMCI subjects (62% females, age 75+/-8 years) and 14 snaMCI subjects (71% females, age 74+/-6 years) underwent [18F]FDG-PET and clinical follow-up. Comparisons between MCI subgroups and with seven cognitively normal elderly subjects were performed using SPM2. RESULTS: At baseline aMCI and snaMCI exhibited a similar pattern of hypometabolism, mostly in the posterior cingulate gyrus, as compared with controls. In the comparison between the MCI subtypes, the aMCI subjects showed reduced metabolism in the medial temporal lobes (MTL) (hippocampus, fusiform gyrus and amygdala). At follow-up 12 aMCI developed Alzheimer's disease (AD), while snaMCI had a heterogeneous course, including five subjects who developed Lewy body dementia. CONCLUSIONS: The patterns of altered brain metabolism in aMCI and snaMCI subjects compared to controls are similar and do not provide evidence for making clinical distinctions between them. Comparison between the two MCI subtypes showed MTL hypometabolism in aMCI subjects, possibly reflecting the fact that most had prodromal AD.

Cholinergic balance in dementia with Lewy bodies: reversible worsening of Parkinsonism at rivastigmine dosage modulation.

We describe a patient with probable dementia with Lewy bodies (DLB) whose Parkinsonism worsened after administration of rivastigmine within the therapeutic dose range. Some extrapyramidal signs (EPS) then reversed to pre-treatment level after rivastigmine dose reduction. We draw attention to the need of EPS monitoring during titration of cholinesterase inhibitors in patients with DLB. This is the first report to our knowledge of iatrogenic worsening of Parkinsonism which was successfully managed by dose reduction.

Allodynia in different forms of migraine.

About 60% of patients complain of cutaneous allodynia during migraine episodes, often in the periorbitary region of the pain side. Pre-clinical studies have shown that the underlying mechanism is sensitisation of primary nociceptors and central trigeminovascular neurons and that patients have a lower pain threshold for mechanical stimulation compared to controls. The objective of this study was to determine the prevalence of allodynia during headache attacks in different forms of migraine. The subjects were 221 outpatients consecutively evaluated in the Headache Center of the L. Sacco Hospital in Milan: 114 had only attacks of migraine without aura (MO), 63 had also attacks with aura (MA) and 44 patients with chronic migraine with and without drug overuse (CM). Presence of head allodynia was investigated by a semistructured interview. Statistical analysis was performed by chi square test with Bonferroni correction for multiple comparisons. Forty-seven out of 114 MO patients (41.2%) complained of allodynia during headache episodes, 41 out of 63 MA patients (65.0%), and 29 out of 44 CM patients (65.9%). A higher frequency of allodynia in MA and CM with respect to MO patients was observed (p<0.01 at chi square test). Allodynia was a common complaint in migraineurs, being present in more than 40% patients of each group. A higher frequency was observed in MA and in CM patients. This observation may suggest that both frequency of attacks and presence of aura episodes may contribute to induce changes in neuronal activation threshold thought to sustain allodynia.

Frontotemporal dementia.

Frontotemporal dementia is a clinicopathological syndrome caused by progressive degeneration of the frontal lobes, anterior temporal lobes or both. A wide spectrum of cognitive, psychological and behavioural symptoms has been reported, with early disturbance of personality and social conduct, impairment of executive functions and language, while memory and visuo-spatial skills are usually preserved. Published criteria can lead to a good accuracy in the antemortem diagnosis of frontotemporal dementia with a sensitivity of 85% and a specificity of 99%. Treatment rests on the management of behavioural disturbances.