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Background Caring for a partner or family member with Parkinson’s disease (PD) negatively affects the caregiver’s own physical and emotional well-being, especially those caring for people with advanced PD (APD). This study was designed to examine the impact of APD on caregiver perceived burden, quality of life (QoL), and health status. Methods Dyads of people with PD and their primary caregivers were identified from the Adelphi Parkinson’s Disease Specific Program (DSP™) using real-world data from the United States, Japan and five European countries. Questionnaires were used to capture measures of clinical burden (people with PD) and caregiver burden (caregivers). Results Data from 721 patient-caregiver dyads in seven countries were captured. Caregivers had a mean age 62.6 years, 71.6% were female, and 70.4% were a spouse. Caregivers for people with APD had a greater perceived burden, were more likely to take medication and had lower caregiver treatment satisfaction than those caring for people with early or intermediate PD; similar findings were observed for caregivers of people with intermediate versus early PD. Caregivers for people with intermediate PD were also less likely to be employed than those with early PD (25.3% vs 42.4%) and spent more time caring (6.6 vs 3.2 h/day). Conclusions This real-world study demonstrates that caregivers of people with APD experience a greater burden than those caring for people with early PD. This highlights the importance of including caregiver-centric measures in future studies, and emphasizes the need for implementing treatments that reduce caregiver burden in APD. Trial registration: N/A.

In order to assess the risk of hypertension development, we performed a retrospective analysis of the clinical records of consecutive transgender patients who began gender-affirming hormonal therapy in our Outpatient Gender Identity Clinic with30 years of age and had a follow-up5 years. 149 transgender women treated with estradiol and 153 transgender men treated with testosterone were included; 129 of the transgender women received also androgen blockers (54 spironolactone, 49 cyproterone acetate and 26 LHRH agonists). The annual incidence of hypertension in young transgender men (1.18%) seemed comparable to that of the general population. In young transgender women, it seemed higher (2.14%); we found that the choice of androgen blocker had a remarkable effect, with a highly significant increase in patients treated with cyproterone acetate (4.90%) vs. the rest (0.80%); the adjusted hazard-ratio was 0.227 (p = 0.001). Correlation, logistic regression and mediation analyses were performed for the associations of the available clinical variables with the increase in systolic blood pressure and the onset of hypertension, but besides the use of cyproterone acetate, only the ponderal gain was found significant (Spearman's r: 0.361, p 0.001); with a 36.7% mediation effect (31.2-42.3%). Cyproterone acetate has additional known risks, such as meningioma; although we cannot conclusively prove that it has a role in the development of hypertension, we conclude that the use of cyproterone acetate for this indication should be reconsidered.

This paper presents an augmented reality application to assist with myoelectric prostheses control for people with limb amputations. For that, we use the low-cost Myo armband coupled with low-level signal processing methods specifically built to control filters’ levels and processing chain. In particular, we use deep learning techniques to process the signals and to accurately identify seven different hand gestures. From that, we have built an augmented reality projection of a hand based on AprilTag markers that displays the gesture identified by the deep learning techniques. With the aim to properly train the gesture recognition system, we have built our own dataset with nine subjects. This dataset was combined with one publicly available to work with the data of 24 subjects in total. Finally, three different deep learning architectures have been comparatively studied, achieving high accuracy values (being 95.56% the best one). This validates our hypothesis that it is possible to have an adaptive platform able to fast learn personalized hand/arm gestures while projecting a virtual hand in real-time. This can reduce the adaptation time to myoelectric prostheses and improve the acceptance levels. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work has been partly supported by Grant PID2019-104818RB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”; and by Generalitat Valenciana (CIGE/2021/136).

Dementia have substantial negative impact on the affected individual, their care partners and society. Persons living with Parkinson’s disease (PwP) are also to a large extent living with dementia. The aim of this study is to estimate time to dementia in PD using data from a large quality register with access to baseline clinical and patient reported data merged with Swedish national health registries. Persons with Parkinson’s disease in the Swedish Neuro Registries/Parkinson’s Disease Swedish PD Registry (PARKreg) in Sweden were included and linked to national health registries and matched by sex and age to controls without PD. Time to dementia was analysed with Cox regression models assuming proportional hazards, with time since diagnosis as the underlying time variable. In this large prospective cohort study, PwP had approximately four times higher risk of developing dementia as compared to age and sex-matched controls, a finding which remained after adjusting for potential confounders. The present results underline the high risk of dementia in PD and further emphasize the importance of developing symptomatic and ultimately disease modifying strategies to counteract this part of the non-motor symptomatology in PD.

Background The aim of this study was to analyze the shoulder functional profile (rotation range of motion [ROM] and strength), upper and lower body performance, and throwing speed of U13 versus U15 male handball players, and to establish the relationship between these measures of physical fitness and throwing speed. Methods One-hundred and nineteen young male handball players (under (U)-13 (U13) [n = 85]) and U15 [n = 34]) volunteered to participate in this study. The participating athletes had a mean background of sytematic handball training of 5.5 ± 2.8 years and they exercised on average 540 ± 10.1 min per week including sport-specific team handball training and strength and conditioning programs. Players were tested for passive shoulder range-of-motion (ROM) for both internal (IR) and external rotation (ER) and isometric strength (i.e., IR and ER) of the dominant/non-dominant shoulders, overhead medicine ball throw (OMB), hip isometric abductor (ABD) and adductor (ADD) strength, hip ROM, jumps (countermovement jump [CMJ] and triple leg-hop [3H] for distance), linear sprint test, modified 505 change-of-direction (COD) test and handball throwing speed (7 m [HT7] and 9 m [HT9]). Results U15 players outperformed U13 in upper (i.e., HT7 and HT9 speed, OMB, absolute IR and ER strength of the dominant and non-dominant sides; Cohen’s d: 0.76–2.13) and lower body (i.e., CMJ, 3H, 20-m sprint and COD, hip ABD and ADD; d: 0.70–2.33) performance measures. Regarding shoulder ROM outcomes, a lower IR ROM was found of the dominant side in the U15 group compared to the U13 and a higher ER ROM on both sides in U15 (d: 0.76–1.04). It seems that primarily anthropometric characteristics (i.e., body height, body mass) and upper body strength/power (OMB distance) are the most important factors that explain the throw speed variance in male handball players, particularly in U13. Conclusions Findings from this study imply that regular performance monitoring is important for performance development and for minimizing injury risk of the shoulder in both age categories of young male handball players. Besides measures of physical fitness, anthropometric data should be recorded because handball throwing performance is related to these measures., Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe; 803

Sialorrhoea in Parkinson’s disease (PD) is an often neglected yet key non-motor symptom with impact on patient quality of life. However, previous studies have shown a broad range of prevalence figures. To assess prevalence of drooling in PD and its relationship to quality of life, we performed a retrospective analysis of 728 consecutive PD patients who had a baseline and follow-up assessment as part of the Non-motor International Longitudinal Study (NILS), and for whom drooling presence and severity were available, assessed through the Non-Motor Symptoms Scale (NMSS). In addition, we analysed the prevalence of associated dysphagia through self-reported outcomes. Quality of life was assessed through the PDQ-8 scale. Baseline (disease duration 5.6 years) prevalence of drooling was 37.2% (score ≥ 1 NMSS question 19), and after 3.27 ± 1.74 years follow-up, this was 40.1% (p = 0.17). The prevalence of drooling increased with age (p p = 0.12). While in 456 patients without drooling at baseline, only 16% (n = 73) had dysphagia (question 20 of the NMSS), in those with drooling this was 34.3% (p r = 0.199; p

The production of synthesis gas via the conversion of the two greenhouse gases CO2 and CH4 is an efficient process due to its dual industrial and environmental interest. The catalysts based on Ni–SiO2 and Ni–Al2O3 are typical and suitable for this reaction due to their mechanical strength, their good chemical and thermal stability in addition to their low cost and good availability. In this work, we have compared the catalytic performances of these two types of catalysts prepared by two different synthesis methods in dry reforming of methane (DRM).The results indicate that the catalytic performances are much more dependent on the support properties and that they are deeply influenced by the catalyst synthesis method. The textural properties as shown by N2-physisorption analysis are strongly dependent on the support nature in the case of the catalysts prepared by the microemulsion (ME) method and the alumina-based Ni catalyst has a higher specific surface area and a higher pore volume compared to the SiO2 based one. The XRD, H2-TPR and XPS results indicate that the preparation method has a significant influence on the state of NiO species. A Ni particle in the two Ni–SiO2–ME and Ni–Al2O3–ME catalysts prepared by microemulsion is much smaller. The strong metal support interaction promotes the formation of NiAl2O4 and Ni2SiO4 species respectively during the catalyst preparation process and makes the reduction of corresponding catalysts very difficult which may lead to a decrease in the content of active Ni species and give the Ni–Al2O3–ME catalyst a relatively low catalytic activity in DRM, especially when it is reduced under unfavorable conditions as is the case in this work. However, the strong metal support interaction between Ni and the support is also of beneficial to the formation and stabilization of small Ni particles well dispersed on the support after reduction of the Ni–SiO2–ME catalyst. In this system, the sintering and the carbon deposition are inhibited and the catalyst presents both better activity and stability. The Ni/Al2O3 catalyst exhibits a synergistic effect between the various phases NiO and NiAl2O4 formed during the synthesis process due to the different interactions strength between metal and support, which are in favor of the dispersion and stabilization of NiO species. As a result, Ni/Al2O3 provided with both proper textural properties and this synergistic effect, exhibits superior catalytic performances in term of activity, selectivity and stability in DRM. Despite the formation of carbon over this catalyst, it maintains its stability during a long-term test of more than 66 hours. This is due to the formation of active type of carbon and the delocalization of the Ni active sites on the latter to maintain their activity.

Sexual dysfunction is a major non-motor feature of Parkinson’s disease (PD) that may affect the quality of life of many patients. In a Dutch survey, we demonstrated that neurologists often fail to discuss sexuality with their patients. Our objective was to determine to which extent neurologists in Spain and Germany address sexuality with their patients and whether cross-cultural differences exist. A 30-item questionnaire was sent out to 1650 German and 460 Spanish neurologists. The questionnaire addressed attitudes, knowledge, barriers, and feelings of responsibility regarding sexuality in PD. 160 German and 32 Spanish respondents completed and returned the questionnaire. The majority of German and Spanish participants discuss sexual dysfunction ‘regularly’ with male patients (61.7% and 78.9%, respectively), but ‘seldom’ with female patients (68.8% and 78.1%, respectively). Important barriers for German and Spanish respondents to discuss sexual dysfunction were patients not expressing sexual complaints spontaneously (52.9% and 75.0%, respectively) and insufficient consultation time (32.2% and 71.9%, respectively). Sexual dysfunction in PD was considered important by 68.3% of German and 96.9% of Spanish participants. German and Spanish neurologists do not routinely discuss sexual dysfunction with their patients, although many of them consider it important to address this topic. It is unclear why this lack of discussing sexual dysfunction is especially found for female patients and whether cultural aspects are involved. We recommend a self-assessment tool for patients to track their symptoms prior to consultation visits and advocate local guidelines that formulate who is responsible for discussing sexual dysfunction. Electronic supplementary material The online version of this article (10.1007/s00702-019-02053-5) contains supplementary material, which is available to authorized users.

While several studies have investigated the clinical progression of cognitive decline in Parkinson’s disease (PD) patients, there has been a paucity of data on specifically evaluating PD patients with a disease duration of over 20 years. This study retrospectively investigated the frequency of dementia in PD (PDD) patients with a disease duration of over 20 years assessed in research clinics across the UK and Australia. Data from 2327 PD patients meeting the United Kingdom Parkinson’s Disease Society Brain Bank Criteria was pooled. A diagnosis of probable PDD was made according to the Movement Disorder Society Level 1 criteria. Thirty-six participants had a disease duration of at least 20 years. Of the 36 patients, only 7 (19%) were classified as probable PDD. Compared to PD patients without dementia, those with dementia had lower levels of educational attainment and exhibited more severe motor features. Additionally, 34 out of the 36 patients (94%) exhibited a non-tremor dominant phenotype. No significant differences in age, age onset, disease duration, dopaminergic medication use, and sex distribution were observed between PD patients with and without dementia. Findings from the present study suggest that the prevalence of dementia in long-term PD patients may be lower than anticipated and suggest that the trajectory of cognitive decline in PD patients can be different. These findings highlight the need to investigate factors that might affect the outcome of cognitive decline in long-term PD patients, which may lead to the determination of potential modulating factors in the development of dementia in these patients.

Having an appropriate tool for assessment of the balance status during the drug off-phase in idiopathic Parkinson’s disease (PD) is relevant for clinical and research settings. Our objective was to assess the clinimetric properties of the Berg balance scale (BBS) during drug off-phase in PD. Balance of 98 PD patients (mean age ± SD, 59.19 ± 10.88 years) was evaluated with the BBS. Other assessments in the study included the Fall Efficacy Scale-International (FES-I), Functional Reach Test (FRT), Section II of the Unified Parkinson’s Disease Rating Scale-3.0, Parkinson’s Disease Questionnaire-39 (PDQ-39), and Schwab and England Activities of Daily Living Scale. All evaluations took place during the drug off-phase. Internal consistency and inter- and intra-rater reliability were evaluated by Cronbach’s alpha coefficient and intraclass correlation coefficient, respectively. Dimensionality was explored by factor analysis. Discriminative validity was tested by comparing BBS score between PD patients with and without a history of falling. Internal consistency was high (α = 0.98), as were intra- and inter-rater reliability (ICC = 0.98 and 0.95, respectively). Factor analysis identified only one dimension for the BBS, whose convergent validity with FES-I, FRT, and domain mobility of the PDQ-39 were moderate or high (rS = |0.60–0.74|). Correlation of BBS with functional scales and PDQ-39 Summary Index was moderate (rS = |0.45–0.62|). Finally, the BBS showed a moderate strength to discriminate between PD patients with and without a history of falling. Our study suggests that BBS has satisfactory internal consistency, reliability, and construct validity for measuring functional balance in people with PD during the drug off-phase.

Impulse control behaviors are a frequent comorbidity for patients with Parkinson’s disease (PD). The objective of the present study was to evaluate the effectiveness levodopa–carbidopa intestinal gel (LCIG) therapy on impulse control disorders (ICDs) in patients with advanced PD. We conducted a multicenter, observational, and prospective (6 months follow-up) study that included consecutive PD patients assigned to LCIG through routine medical practice. Patients completed visits at baseline, 1, 3, and 6 months after percutaneous endoscopic gastrostomy procedure. The following outcomes were evaluated: presence and severity of ICDs and other neuropsychiatric disorders, sleep disturbances, patients’ quality of life, and caregivers’ burden. Sixty-two patients were included at baseline: mean age 72.2 years (SD ± 7.0), 42% women. Median duration of PD symptoms was 13.5 years (IQR 5.5–21.5) and median time with motor fluctuations was 5.0 years (IQR 1.0–9.0). Treatment with LCIG infusion was associated with progressive and significant improvements in ICDs symptoms over the study period (64.4% reduction in the Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s disease—Rating Scale score). Psychotic and other neuropsychiatric symptoms were also significantly reduced, and patients’ sleep quality and psychosocial function improved. Caregivers’ burden remained unchanged. There was a significant improvement in the daily “Off” time [7.4 h (SD ± 4.0) vs 1.5 h (SD ± 1.8); p

Genetic engineering by viral infection of single cells is useful to study complex systems such as the brain. However, available methods for infecting single cells have drawbacks that limit their applications. Here we describe 'virus stamping', in which viruses are reversibly bound to a delivery vehicle - a functionalized glass pipette tip or magnetic nanoparticles in a pipette - that is brought into physical contact with the target cell on a surface or in tissue, using mechanical or magnetic forces. Different single cells in the same tissue can be infected with different viruses and an individual cell can be simultaneously infected with different viruses. We use rabies, lenti, herpes simplex, and adeno-associated viruses to drive expression of fluorescent markers or a calcium indicator in target cells in cell culture, mouse retina, human brain organoid, and the brains of live mice. Virus stamping provides a versatile solution for targeted single-cell infection of diverse cell types, both in vitro and in vivo.

The regulation of size, volume and mass in living cells is physiologically important, and dysregulation of these parameters gives rise to many diseases. Cell mass is largely determined by the amount of water, proteins, lipids, carbohydrates and nucleic acids present in a cell, and is tightly linked to metabolism, proliferation and gene expression. Technologies have emerged in recent years that make it possible to track the masses of single suspended cells and adherent cells. However, it has not been possible to track individual adherent cells in physiological conditions at the mass and time resolutions required to observe fast cellular dynamics. Here we introduce a cell balance (a 'picobalance'), based on an optically excited microresonator, that measures the total mass of single or multiple adherent cells in culture conditions over days with millisecond time resolution and picogram mass sensitivity. Using our technique, we observe that the mass of living mammalian cells fluctuates intrinsically by around one to four per cent over timescales of seconds throughout the cell cycle. Perturbation experiments link these mass fluctuations to the basic cellular processes of ATP synthesis and water transport. Furthermore, we show that growth and cell cycle progression are arrested in cells infected with vaccinia virus, but mass fluctuations continue until cell death. Our measurements suggest that all living cells show fast and subtle mass fluctuations throughout the cell cycle. As our cell balance is easy to handle and compatible with fluorescence microscopy, we anticipate that our approach will contribute to the understanding of cell mass regulation in various cell states and across timescales, which is important in areas including physiology, cancer research, stem-cell differentiation and drug discovery.

BACKGROUND: Self-rated health (SRH) is a health measure used in studies of older adults. The objective of this study is to analyze SRH as a predictor of mortality in the institutionalized older population and the characteristics of those who do not provide information about their SRH on health questionnaires. METHODS: This is a 15-year follow-up study of older adult residents in nursing or care homes in of Madrid, Spain. SRH was measured on a 5-point Likert type scale. The association between answering the SRH question and socio-demographic and health characteristics was evaluated through prevalence ratio (PR), estimated by Poisson regression models. Survival rates associated with SRH were studied through a multivariate Cox regression. RESULTS: The sample has a mean age of 83.4 (standard deviation, SD = 7.3), with 75.7% women. Twelve percent did not answer the SRH item. Those who did not answer showed a higher probability of disability (Barthel index, PR = 0.76, 95% confidence interval = 0.67-0.86) and/or dementia (PR = 8.03, 3.38-19.03). A trend for higher mortality was observed in those persons who did not respond (adjusted hazard ratio HR = 1.26, 0.75-2.11). The mortality rate was 32% higher for those who declared poor SRH in comparison with those who reported good SRH (adjusted HR = 1.32, 1.08-1.6). CONCLUSIONS: There is an elevated number of people who do not respond to the SRH item, mainly those with disabilities and cognitive deterioration. Lack of response to SRH is a good indicator of 15-year mortality for persons institutionalized in care or nursing homes. This work was supported by the Institute of Health Carlos III (grant number, PI15CIII00037) and partially supported by the ENCAGE-CM programme (ref: S2015/HUM-3367, co-funded by Madrid Community and FEDER). The funding bodies did not have any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Sí

Digital phenotyping uses smartphone and wearable signals to measure cognition, mood, and behavior. This promising new approach has been developed as an objective, passive assessment tool for the diagnosis and treatment of mental illness. Digital phenotyping is currently used with informed consent in research studies but is expected to expand to broader uses in healthcare and direct-to-consumer applications. Digital phenotyping could involve the collection of massive amounts of individual data and potential creation of new categories of health and risk assessment data. Because existing ethical and regulatory frameworks for the provision of mental healthcare do not clearly apply to digital phenotyping, it is critical to consider its possible ethical, legal, and social implications. This paper addresses four major areas where guidelines and best practices will be helpful: transparency, informed consent, privacy, and accountability. It will be important to consider these issues early in the development of this new approach so that its promise is not limited by harmful effects or unintended consequences.

Data on frequency, severity and correlations of NMS with motor complications are only available for a limited number of NMS. The NMS Scale (NMSS) is a validated tool to assess a broad range of NMS, which has not been used in NMS fluctuations. We assessed fluctuations of a broad range of non-motor symptom (NMS) for a 1-month time period in fluctuating Parkinson's disease (PD) in a multicenter cross-sectional study using the NMSS assessing NMS in motor On (NMSSOn) and Off state (NMSSOff) combined with clinical NMS and motor function scoring in 100 fluctuating PD patients. ΔNMSSOn/Off was defined as the differences of NMSS scores between On and Off. Complete NMSS datasets were available from 73 patients (53 % men; age: 68.2 ± 9.7 years) with mean total NMSS score in On state of 41.5 ± 37.6 and in Off state of 75.6 ± 42.3 (P < 0.001). Scores were higher in Off compared to On state for all domains except for domain "perceptual problems/hallucinations" (P = 0.608). Clinimetric properties of the NMSS were similar to those reported previously for NMS assessments independent of motor oscillations. NMSSOn, NMSSOff and ΔNMSSOn/Off showed weak to moderate correlations with demographics, indicators of motor symptom severity as well as with other measures of NMS, depression and quality of life. Correlations of NMSS items/domains with independent measures of related constructs were weak to moderate. In conclusion, when assessed with the NMSS, a broad range of NMS fluctuate with motor oscillations, but these fluctuations do neither correlate with motor function nor with measures of disease progression.

Quality of life (QoL) is a patient-reported outcome frequently included in Parkinson's disease (PD) clinical trials as a secondary or tertiary endpoint. However, QoL is an important variable that reflects the impact of disease and treatment from the patients' perspective. In a chronic, neurodegenerative disease such as PD, with a wide range of complex symptoms, QoL provides valuable and comprehensive information on the patients' health status. This narrative review aims to evaluate the effect of specific PD treatments currently in use on patients' QoL measured with the Parkinson's Disease Questionnaire, 39-item (PDQ-39) or 8-item (PDQ-8) version. A quantification of this effect is provided by calculation of the relative change and effect size. These two parameters allow an intuitive standardized approach to the importance of change based on its magnitude. Some high-quality studies (Level I) were found for levodopa (immediate- or extended-release formulations), levodopa with added-on catechol-O-methyltransferase (COMT) inhibitors, levodopa/carbidopa gel for intestinal infusion, some dopamine agonists (ropinirole, cabergoline, pergolide), and the monoamine oxidase B (MAO-B) inhibitor safinamide. As a whole, these studies found a beneficial effect of variable magnitude, weak to moderate, on patients' QoL. Studies with a lower level of evidence or not providing enough data to estimate relative change and effect size, including those for the apomorphine subcutaneous pump, also reported improvement of QoL, but the evidence was insufficient to confirm the effect. More high-quality studies focused on QoL are needed to determine the real impact of PD drug treatments for this important outcome.

Sleep disorders are very prevalent in Parkinson's disease (PD) and include a diversity of disturbances. Rating scales and questionnaires are widely used to assess the presence and severity of the sleep disorders. The objective is to review rating scales and questionnaires used for assessment of sleep disorders in PD. To this purpose, a description and update of the sleep scales reviewed by the ad hoc Movement Disorder Society task force (MDS-TF) and other sleep disorder assessments was performed. Two specific (Parkinson's Disease Sleep Scale and Scales for Outcomes in PD Sleep) and two generic scales (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale) were "Recommended" by the MDS-TF as they were used in PD patients, by researchers others than their developers and properly validated. Two other generic scales (Inappropriate Sleep Composite Score and Stanford Sleepiness Scale), "Suggested" due to incomplete validation, are also reviewed. Other instruments included in this review are three comprehensive PD-specific instruments for assessing multiple domains in addition to sleep problems (e.g., Non-Motor Symptoms Questionnaire, Non-Motor Symptoms Scale, MDS-UPDRS), and three generic instruments focused on particular disturbances (e.g., International Restless Legs Syndrome Study Group Rating Scale, REM behavioral disorders questionnaires), although these latter lack formal validation in PD populations. The "Recommended" instruments cover satisfactorily the needs for screening and evaluation of the nocturnal sleep disorders and daytime sleepiness in PD patients. It would be convenient to validate or complete the validation in PD populations of those instruments that cannot be recommended due to the lack of information on their clinimetric attributes.

Alzheimer’s disease (AD), the most prevalent disorder causing dementia, is considered a neurodegenerative disease. The cause is unknown for over 95 % of the cases who do not have a genetic disease and the pathogenetic mechanisms are incompletely known. The main hypotheses to explain the lesions and the decline in brain functioning are the amyloid cascade and the abnormal phosphorylation of tau protein, which are the grounds for the typical AD lesions: senile plaques and neurofibrillary tangles. Some observations, however, indicate that the relationship between those mechanisms, structural changes, and cognitive state is not univocal or specific. On the other hand, age at onset and clinical presentation are quite variable, as is the duration of the disease. As a matter of fact, a wide differential diagnosis may be necessary and, in the absence of a reliable diagnostic marker, the adscription to widely accepted criteria is compulsory. Nonetheless, the accuracy of the usually applied diagnostic criteria is around 80–90 %. From a nosologic perspective, the current clinicopathological concept of AD, with unknown etiology, hypothetically variable pathogenesis, and wide clinical variability, justifies considering AD in a comprehensive manner. Therefore, a disorder primarily affecting structures in medial temporal lobe, with accumulation of amyloid β and abnormal tau, neuritic plaques and tangles, progressive loss of memory and/or other cognitive deficits, ultimately resulting in dementia should be classified as AD. Hopefully, scientific advances (in genetics, proteomics, metabolomics, etc.) will allow a more precise definition of the disease in the future.