Published in last 50 years
Articles published on Psychobehavioral Symptoms
- New
- Abstract
- 10.1210/jendso/bvaf149.594
- Oct 22, 2025
- Journal of the Endocrine Society
- Kananart Poolpong + 2 more
Disclosure: K. Poolpong: None. S. Siriwong: None. T. Raomanachai: None.DiGeorge syndrome (22q11.2 deletion syndrome) is typically diagnosed in childhood due to congenital cardiac anomalies, hypocalcemia, immune deficiency, or craniofacial features. Adult-onset hypocalcemia as the first clinical manifestation remains exceptionally rare. We report a 43-year-old Thai male with no known childhood developmental concerns who presented with acute carpal spasms. Biochemical evaluation revealed hypocalcemia (serum calcium 6.24 mg/dL), low phosphate, and inappropriately normal PTH (23.1 pg/mL), indicating primary hypoparathyroidism. His past medical history included treated thyrotoxicosis. Physical examination revealed positive Chvostek and Trousseau signs, a harsh pansystolic murmur grade 3/6 at the left mid and lower parasternal border, cleft palate with dental loss, and mild bilateral sensorineural hearing loss. ECG showed QTc prolongation (488 ms), and echocardiography confirmed a small perimembranous ventricular septal defect. Genetic testing via FISH confirmed a 22q11.2 microdeletion, establishing the diagnosis of DiGeorge syndrome. He was treated with intravenous calcium followed by oral calcium carbonate and calcitriol, with resolution of symptoms and normalization of serum calcium. This case is noteworthy for the absence of classical phenotypic clues in childhood and the unusually late onset of hypocalcemia as the first clinical trigger. Compared to other adult DiGeorge cases, our patient had no prior seizures, psychobehavioral symptoms, or neonatal hypocalcemia. Instead, the diagnosis was guided by careful clinical examination and interpretation of subtle features such as cleft palate and congenital murmur. To our knowledge, this case represents one of the latest-age first clinical presentations of DiGeorge syndrome, where isolated hypocalcemia initiated diagnosis. This highlights the importance of considering congenital syndromes such as DiGeorge syndrome in adults with unexplained hypoparathyroidism, especially without history of neck surgery or other causes. Recognition of the 22q11.2 deletion changed the patient's management plan, prompting cardiac surveillance, audiologic support, and genetic counseling. This case underscores the pivotal role of thorough physical examination in uncovering subtle syndromic features that might otherwise go unrecognized. Timely diagnosis not only guides appropriate calcium replacement but also prompts lifelong surveillance and anticipatory care across specialties. Although current guidelines do not recommend routine genetic screening in adult hypocalcemia, this case demonstrates how phenotype-driven clinical judgment can guide appropriate testing and reveal overlooked congenital syndromes.Presentation: Saturday, July 12, 2025
- Research Article
- 10.1016/j.parkreldis.2025.107953
- Sep 1, 2025
- Parkinsonism & related disorders
- Tian Xu + 10 more
Cognitive function, psychobehavioral symptoms, and MRI features in patients with non-demented Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies.
- Research Article
- 10.1016/j.sger.2025.02.009
- Feb 1, 2025
- Soins. Gerontologie
- Éric Maeker + 1 more
Systemic approach to psychobehavioral symptoms in the elderly with neurocognitive disorders
- Research Article
1
- 10.1186/s12877-024-05562-5
- Dec 19, 2024
- BMC Geriatrics
- Simona Cintoli + 5 more
Backgroundinformal caregivers of people with dementia are at greater risk of developing physical and mental health problems when compared to the general population: they often experience high levels of stress which can lead to a lowered sense of well-being, feelings of being burdened, depression and compromised physical health. The significant beneficial effects of Psychoeducational Interventions on the critical outcomes of caregiver burden and strain were considered sufficient to warrant a recommendation in favour of the intervention. The emergence of the COVID-19 pandemic has significantly increased the use internet-based interventions: this study describes the effectiveness of support program for informal caregivers of people with dementia internet-based and on-site conditions.MethodsA Psychoeducational Interventions program, consisting of 5 meetings every 2 weeks, has been structured. It aims to provide information and strategies for managing cognitive and psycho-behavioral symptoms in neurodegenerative diseases, as well as to develop effective communication skills and understanding of the caregiver's experience. Intervention formats include slides, video, group discussions and are always led by a psychologist. We assessed in 73 caregivers (33 internet-based and 40 on-site conditions) level of Behavioural and Psychological Symptoms of Dementia management, dementia awareness, social support, find leisure time, harmony with relative, stress, with Visual-Analogue Scale at the beginning of PI and at the end. During the pandemic period the protocol was adapted to be available online and subsequently proposed to caregivers belonging to the Cognitive Disorders and Dementia Centre.Resultsin both modalities, internet-based and on-site condition, a statistically significant improvement was highlighted in all aspects (p < 0.05, for all p-value). Questionnaire on basic dementia knowledge was successfully completed at 100%. Also, participants reported a medium to high level of satisfaction with very limited dropouts (< 3%).ConclusionsThe evidence from this pilot study indicated that caregiver support interventions in both conditions significantly improved several and important outcomes: they showed a significant effect in reducing caregiver strain and improving ability and knowledge. Indeed, Psychoeducational Interventions contribute to effective coping strategies to mitigate caregiver burden so they can continue to provide care for loved ones.
- Research Article
- 10.3390/geriatrics9060162
- Dec 14, 2024
- Geriatrics (Basel, Switzerland)
- Akihiko Asao + 11 more
Background/Objectives: Maintaining functional independence and minimizing disability among older adults living in the community is paramount for mitigating rising care demands. Our study focused on shopping as a critical instrumental activity of daily living (ADL) to explore the association between shopping assistance and functional decline among older individuals receiving support through long-term care insurance (LTCI). Methods: This retrospective, cross-sectional study included 6202 participants aged >65 years living in a Japanese regional town receiving LTCI support, suggesting that they required assistance with local community life. Logistic regression analysis identified several factors associated with shopping assistance among the participants, including physical and cognitive functions, functional ADL, and psychobehavioral symptoms. Results: In male participants, walking dysfunction, short-term memory decline, decreased frequency of going outdoors, and decreased engagement in personal grooming were significantly associated with requiring shopping assistance. Conversely, in female participants, reduced physical function and walking performance were significantly associated with requiring shopping assistance, whereas dependence on personal grooming was less pronounced than in male participants. Conclusions: These findings suggest that, in addition to direct shopping assistance, tailored interventions targeting physical, cognitive, and ADL functions-while considering gender-specific needs-may help older adults maintain independence in shopping activities as part of their daily community life.
- Research Article
- 10.1007/s11064-024-04270-1
- Nov 19, 2024
- Neurochemical Research
- Dayuan Lao + 4 more
The clinical manifestations of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis may be closely related to the integrity of the blood–brain barrier (BBB). The P38 mitogen-activated protein kinase (P38MAPK) pathway plays a protective role in neurodegenerative diseases. However, whether the P38MAPK pathway is involved in the underlying mechanism of tight junction (TJ) protein disruption and neuronal damage has not been elucidated. Therefore, in this study, a mouse model of anti-NMDAR encephalitis was established by active immunization with NMDAR NR1356-385 peptides. The critical pathways of P38MAPK were screened by interaction network and co-enrichment analysis. The role of P38MAPK pathways was investigated by the injection of P38MAPK inhibitor SB203580 (10 mg/kg, i.p.). Compared with the control group, the expression of occludin and zonula occludens (ZO)-1 in NMDAR NR1356-385 group mice was downregulated, and the structure and function of BBB were damaged. However, after the intervention of SB203580, the activation of the P38MAPK was inhibited, the expression of matrix metalloproteinase 9 (MMP9) was reduced, and the function of BBB was improved. Meanwhile, inhibiting the P38MAPK pathway reversed the degradation of NMDAR NR1, while reducing the expression of the glial fibrillary acidic protein (GFAP) and pro-inflammatory factor tumor necrosis factor (TNF-α). It also relieved the damage of neuron-specific nucleus (NeuN), thus alleviating psychobehavioral symptoms. In conclusion, our results suggested that the P38MAPK pathway is involved in BBB destruction and neurobehavioral change in mice with anti-NMDAR encephalitis. Targeting the P38MAPK pathway may be a promising option for the treatment of anti-NMDAR encephalitis.
- Research Article
- 10.1016/j.jamda.2024.105363
- Nov 17, 2024
- Journal of the American Medical Directors Association
- Jonathan D Winter + 11 more
A Nursing Home Clinician Survey to Explain Gabapentinoid Increases
- Research Article
- 10.3389/fneur.2024.1436030
- Oct 2, 2024
- Frontiers in neurology
- Yuan Chen + 6 more
Patients with Alzheimer's disease (AD) often exhibit characteristic clinical manifestations, particularly neuropsychiatric symptoms. Previous studies have shown that white matter hyperintensity (WMH) is strongly associated with AD progression, as well as neuropsychiatric symptoms. The purpose of this study was to investigate the clinical and neuropsychological characteristics of AD patients with WMH. This retrospective study involved 104 18-fluorodeoxyglucose-positron emission computed tomography (18FDG-PET-CT)-defined AD patients treated at Tianjin Huanhu Hospital from January 2010 to December 2022. Cranial magnetic resonance imaging (MRI) provided semi-quantitative data on brain structure and WMH. Collect and analyze patient clinical data. Neuropsychological assessments were used to evaluate cognitive function and psychobehavioral traits. Among the 104 patients, 66 were in the WMH group (63.5%) and 38 in the non-white matter hyperintensity (non-WMH) group (36.5%). There were no significant differences in gender, age, age of onset, education, BMI, smoking, drinking, diabetes, coronary heart disease, dementia family history, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) between the two groups. The WMH group showed higher rates of hypertension, homocysteine (Hcy) levels, NPI, and CDR scores as compared to the non-WMH group (p < 0.05). MMSE and MoCA scores were significantly lower in the WMH group (p < 0.05). In the MMSE subitem analysis, patients in the WMH group showed a decrease in attention, recall, and language scores. In the MOCA subitem analysis, WMH patients had lower scores in executive function, naming, attention, language, abstraction, and orientation (p < 0.05). Furthermore, subgroup analysis of NPI showed a higher incidence of delusions, depression, and apathy in the WMH group (p < 0.05). According to the hierarchical analysis of mild, moderate and severe dementia groups, the hypertension, leukoencephalopathy, Hcy level, Fazekas total score, PWMH and DWMH scores in the severe dementia group were significantly higher than those in the mild and moderate dementia groups (p < 0.05). As the disease progresses, more and more patients show increased white matter hyperintensity. White matter lesions are closely correlated with cognitive decline and psychobehavioral symptoms in AD patients, and may be used as an indicator of disease progression. Priority should be given to early screening and prevention of WMH-related risk factors.
- Research Article
- 10.46235/1028-7221-16669-nbp
- Aug 12, 2024
- Russian Journal of Immunology
- S L Pashnin + 2 more
The formation of post-stress disorders in veterans of modern military conflicts is due to the peculiarities of the mutual influence of mental and immuno-endocrine processes aimed at maintaining the stability of the body in conditions of chronic activation of physiological systems through a process known as allostasis. The purpose of the study was to study the levels of stress mediators of hypothalamic-pituitary and adrenal origin, the cytokine profile of blood of veterans of modern wars with PTSD. 38 veterans of a special military operation in Ukraine with a diagnosis according to ICD 10: PTSD (F43.1) took part in the study. The diagnosis was verified on the basis of neuropsychological and pathopsychological examination. The comparison group included 30 veterans of the Chechen military campaign of the same age. The levels of stress hormones in the blood were determined by ELISA using the following method: ACTH (IBL, Germany); norepinephrine (Cloud-Clone, China); cortisol (HemaMedica, Russia); dihydroepiandrosterone (DBC, Canada). The blood cytokine profile was determined using a multiplex analysis using the Bio-Plex test system (MERZ, Germany). Evidence of the accumulation of “allostatic load” during the formation of PTSD in SVO veterans was an increase in the blood concentrations of ACTH, norepinephrine, and cortisol, which are plastic constants of the catatoxic strategy of adaptation to the effects of prolonged combat stress. Allostatic reactions in PTSD included changes in the cytokine profile of the blood in the form of increased levels of pro-inflammatory cytokines (IL- 1β, IL-6, IL-12 TNFα) and decreased anti-inflammatory and regulatory cytokines (IL-4, IL-10, TGF-β, IL-2). This neuroinflammatory status may be associated with the development of psycho-behavioral symptoms of PTSD. The formation of maladaptive changes with the accumulation of “allostatic load” was clinically expressed in the form of PTSD and was accompanied by changes in the neurocytokine blood profile in the form of increased levels of ACTH, norepinephrine, cortisol, IL-lβ, IL-6, IL-12 TNFα, against the background of a decrease in the concentration of dehydroepiandrosterone, TGF-β, IL-4, IL-10, IL-2, which generally reflects the prevalence of the catatoxic adaptation strategy in combatants.
- Research Article
11
- 10.1097/md.0000000000037799
- Apr 19, 2024
- Medicine
- Yan Chen + 2 more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial. The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis. We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results. All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs. ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
- Research Article
- 10.1016/j.bbii.2024.100060
- Apr 1, 2024
- Brain Behavior and Immunity Integrative
- Lindsey Garfield + 3 more
Protocol for a pilot study assessing a virtual mindfulness intervention for postpartum African American women
- Research Article
1
- 10.3389/fnagi.2023.1302281
- Dec 18, 2023
- Frontiers in aging neuroscience
- Shouzi Zhang + 7 more
Patients with COVID-19 may experience various neurological conditions, including cognitive impairment, encephalitis, and stroke. This is particularly significant in individuals who already have Alzheimer's disease (AD), as the cognitive impairments can be more pronounced in these cases. However, the extent and underlying mechanisms of cognitive impairments in COVID-19-infected AD patients have yet to be fully investigated through clinical and neurophysiological approaches. This study included a total of 77 AD patients. Cognitive functions were assessed using neuropsychiatric scales for all participants, and plasma biomarkers of amyloid protein and tau protein were measured in a subset of 25 participants. To investigate the changes in functional brain connectivity induced by COVID-19 infection, a cross-sectional neuroimaging design was conducted involving a subset of 37 AD patients, including a control group of 18 AD participants without COVID-19 infection and a COVID-19 group consisting of 19 AD participants. For the 77 AD patients between the stages of pre and post COVID-19 infection, there were significant differences in cognitive function and psychobehavioral symptoms on the Montreal Scale (MoCA), the neuropsychiatric inventory (NPI), the clinician's global impression of change (CIBIC-Plus), and the activity of daily living scale (ADL). The COVID-19 infection significantly decreased the plasma biomarker level of Aβ42 and increased the plasma p-tau181 level in AD patients. The COVID-19-infected AD patients show decreased local coherence (LCOR) in the anterior middle temporal gyrus and decreased global correlation (GCOR) in the precuneus and the medial prefrontal cortex. The findings suggest clinical, cognitive, and neural alterations following COVID-19 infection in AD patients and emphasize the need for close monitoring of symptoms in AD patients who have had COVID-19 and further exploration of the underlying mechanisms.
- Research Article
15
- 10.1371/journal.pone.0293977
- Dec 6, 2023
- PLOS ONE
- Lili Zang + 6 more
Although Alzheimer's disease (AD) mainly affects cognitive function, it is often accompanied by sleep disorders and psychobehavioral symptoms. These symptoms, including depression, agitation, and psychotic symptoms, are prominent hospitalization causes among patients with AD. Currently, relatively more research exists on light therapy for sleep disorders, while those on psychobehavioral symptoms are gradually increasing. However, no consensus exists on these results because of the vulnerability of light therapy to multiple factors, including light intensity and duration. Thus, further research investigating this aspect is warranted. To evaluate the efficacy of light therapy in improving sleep disorders and psychobehavioural symptoms in patients with AD. In this meta-analysis, relevant literature was searched in Embase, the Clinical Trials Registry, Web of Science, PubMed, and the Cochrane Library up to December 2022. Furthermore, a fixed-effects model was used for data analysis. Fifteen randomized controlled trials involving 598 patients with AD were included. In the case of sleep disorders, our meta-analysis revealed that light therapy significantly improved sleep efficiency (MD = -2.42, 95% CI = -3.37 to -1.48, p < 0.00001), increased interdaily stability (MD = -0.04, 95% CI = -0.05 to -0.03, p < 0.00001), and reduced intradaily variability (MD = -0.07, 95% CI = -0.10 to -0.05, p < 0.00001). With respect to psychotic behavior, light therapy was found to alleviate depression (MD = -2.55, 95% CI = -2.98 to -2.12, p < 0.00001) as well as reduce agitation (MD = -3.97, 95% CI = -5.09 to -2.84, p < 0.00001) and caregiver burden (MD = -3.57, 95% CI = -5.28 to -1.87, p < 0.00001). Light therapy leads to significant improvement in sleep and psychobehavioral symptoms and is associated with relatively fewer side effects in patients with AD, indicating its potential as a promising treatment option for AD.
- Research Article
- 10.1017/s1041610223003903
- Dec 1, 2023
- International Psychogeriatrics
- Ana Sofia Pozo Vico + 10 more
P7: Institutionalization and Psychotropics
- Abstract
- 10.1016/j.jns.2023.122757
- Dec 1, 2023
- Journal of the Neurological Sciences
- Cristina Polito + 6 more
Beyond motor symptoms: Interaction between clinical-demographic, genetic characteristics and psycho-behavioral symptoms in Huntington’s Disease
- Research Article
1
- 10.1177/10600280231213507
- Nov 24, 2023
- The Annals of pharmacotherapy
- Fuga Habuchi + 4 more
Patients with dementia are prescribed low-dose atypical antipsychotics (AAPs) to treat psycho-behavioral symptoms. Although AAPs are known to cause diabetes mellitus-related adverse events (DMAEs), information regarding AAPs-induced DMAEs experienced by patients with dementia is lacking. To use the Japan Adverse Drug Event Report (JADER) database to assess the onset tendencies and patterns of DMAEs attributable to AAPs prescribed to patients with dementia. We performed an analysis using dementia cases from the JADER database that were registered from April 2004 to December 2022. Data in the JADER database are completely anonymized; thus, we did not require institutional review board approval for using the JADER database in our study. The reporting odds ratio and proportional reporting ratio (PRR) were used to assess the onset tendencies of DMAEs with AAPs. In addition, Weibull shape parameters were used to assess the patterns of DMAEs that occur with the use of AAPs. We identified AAPs associated with DMAEs. In particular, low doses of quetiapine showed the potential to induce DMAEs. An analysis of the onset of DMAEs showed the early failure patterns for AAPs (median onset = 38 days). The AAPs may cause DMAEs in patients with dementia. Low doses of quetiapine may induce DMAEs. Health care workers should focus on the development of DMAEs during the early administration period of AAPs. These results may assist with the safe management of patients with dementia who use AAPs.
- Research Article
- 10.5604/01.3001.0054.3324
- Apr 26, 2023
- Archives of Physiotherapy and Global Researches
- Sneha Panchal + 2 more
Background: Global population ageing is contributing to a growing public health crisis of cognitive impairment (CI), depression, anxiety, and stress. Cognitive dysfunction can affect a variety of cognitive processes, including attention, verbal and nonverbal learning, short-term and working memory, visual and auditory processing, problem-solving, processing speed, and motor functioning. The study aimed to compare the benefits of multi-modal exercise training to choreograph-based exercise training on psycho-behavioural symptoms and cognitive performance in the elderly population. Methods: The populations were distributed using a basic random sampling approach. Eight geriatric groups with cognitive impairment and psycho-behavioural alterations were the subjects of a comparative investigation. Training in choreographed exercises was given to Group A (n = 4), whereas training in multi-modal exercises was given to Group B (n = 4). The study's inclusion requirements required one to be 60 years of age or older. Both genders, MMSE scores 18–30, DASS scores 10–13 for depression, 8–9 for anxiety, and 15–18 for stress. Pre- and post-c Outcome indicators were assessed using MMSE and DASS. Results: A statistically significant (p<0.05) effect was indicated by a within-group examination of all the outcome measures following the intervention. A statistically significant (p<0.05) effect was indicated by a between-group examination of all the outcome measures following the intervention. Exercise training focused on choreography had a greater impact than the other group. Conclusion: The study found that in the senior population, choreograph-based exercise training was superior to multi-modal exercise training in terms of enhancing cognitive function and lowering psycho-behavioural symptoms.
- Research Article
- 10.1016/j.revinf.2023.03.005
- Apr 1, 2023
- La Revue de l'Infirmière
- Blandine Laquet + 2 more
Reconnaître un syndrome confusionnel aigu et des troubles neurocognitifs aux urgences
- Research Article
- 10.62581/revgeri.18128
- Feb 23, 2023
- Revue de gériatrie
- Natalia Shpak-Deschamps + 2 more
Introduction: We conducted a study of the management of behavioral and psychological symptoms of dementia by individual external hydrotherapy in 9 people with dementia syndrome. Method: The general immersion of the person was associated with a whirlpool bath, underwater shower, music therapy and light show, 3 times a week for 2 weeks. The duration of each session was 20 minutes. The water temperature was 36-38°C. Results: We observed the positive effect of multisensory hydrotherapy on psycho-behavioral symptoms in elderly people with dementia, regardless of its ethology. This effect was objectified by the NPI-ES scale. Simultaneous assessment using the Algo+ and EVS scales demonstrated a reduction in chronic pain of osteoarticular origin in these patients. The consumption of analgesic and psychotropic drugs in patients who participated in the study was reduced. The care team expressed unanimous satisfaction with the care provided. Conclusion: It is important to respect the choice of the person to receive the treatment or not, as well as a personalized approach during the treatment. We believe that a study on a larger scale would be desirable in order to confirm the results.
- Research Article
2
- 10.1007/s00415-022-11297-3
- Aug 1, 2022
- Journal of neurology
- Sonia Di Tella + 8 more
Huntington's disease (HD) is a genetic neurodegenerative disease characterized by cognitive, motor, and psychiatric dysfunction. It is caused by an expansion of the trinucleotide repeat sequence cytosine-adenine-guanine (CAG) in the Huntingtin gene on chromosome 4. Onset typically occurs in the fourth or fifth decade, ranging from childhood to late adulthood. The CAG triplet number is generally inversely proportional to the age of onset (AOO), but the repeat number only accounts for ∼70% of the variability in AOO. Several studies demonstrated the impact of genetic modifiers on age of disease onset. In addition to genetics, we also explored the demographic, anamnestic, and socio-environmental factors that can affect AOO, to help us understand the non-genetic variability of age of onset in HD. We analyzed the retrospective data of the ENROLL-HD global registry study, particularly focusing on the continuum of ages, to include sociodemographic, genetic, and anamnestic psychobehavioral variables in a multivariate regression model aimed at identifying the potential predictors of age of motor onset (n = 5053). We ran the same regression model in the sample of subjects who had the same number of triplets (41 CAG, n = 593) and in the sample whose family history was absent/unknown (n = 630). Patients with delayed onset more frequently have unknown/missing family history, are married or widowed, live in larger urbanized contexts and have a lower educational level. Individuals with earlier onset more frequently develop psychobehavioral symptoms. In the past, the HD gene was considered the epitome of genetic determinism. Our results are consistent with recent evidence that other factors might modulate its impact. These findings allow characterizing the determinants of AOO beyond the CAG expansions and provide valuable information for stratifying patients for future clinical trial designs.