Abnormal pain perception is associated with thalamo-cortico-striatal atrophy in C9orf72 expansion carriers in the GENFI cohort.

OBJECTIVE: Frontotemporal dementia (FTD) is typically associated with changes in behaviour, language and movement. However, recent studies have shown that patients can also develop an abnormal response to pain, either heightened or diminished. We aimed to investigate this symptom in mutation carriers within the Genetic FTD Initiative (GENFI). METHODS: Abnormal responsiveness to pain was measured in 462 GENFI participants: 281 mutation carriers and 181 mutation-negative controls. Changes in responsiveness to pain were scored as absent (0), questionable or very mild (0.5), mild (1), moderate (2) or severe (3). Mutation carriers were classified into C9orf72 (104), GRN (128) and MAPT (49) groups, and into presymptomatic and symptomatic stages. An ordinal logistic regression model was used to compare groups, adjusting for age and sex. Voxel-based morphometry was performed to identify neuroanatomical correlates of abnormal pain perception. RESULTS: Altered responsiveness to pain was present to a significantly greater extent in symptomatic C9orf72 expansion carriers than in controls: mean score 0.40 (SD 0.71) vs 0.00 (0.04), reported in 29% vs 1%. No significant differences were seen between the other symptomatic groups and controls, or any of the presymptomatic mutation carriers and controls. Neural correlates of altered pain perception in C9orf72 expansion carriers were the bilateral thalamus and striatum as well as a predominantly right-sided network of regions involving the orbitofrontal cortex, inferomedial temporal lobe and cerebellum. CONCLUSION: Changes in pain perception are a feature of C9orf72 expansion carriers, likely representing a disruption in somatosensory, homeostatic and semantic processing, underpinned by atrophy in a thalamo-cortico-striatal network.

The Quadruple Helix-Based Innovation Model of Reference Sites for Active and Healthy Ageing in Europe: The Ageing@Coimbra Case Study.

Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources (2,243,934 inhabitants, 530,423 aged 65 or plus live in the Centre Region of Portugal). Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement, across Europe, is inspired by the quadruple helix concept and by the replication of innovative good practices; creating new Reference Sites for the benefit of Citizens.

Do MCI patients with vitamin B12 deficiency have distinctive cognitive deficits?

BACKGROUND: Vitamin B12 deficiency is common in older people, and may be responsible for reversible dementia. Low serum vitamin B12 levels were also observed in patients with Mild Cognitive Impairment (MCI). It is not known whether patients with vitamin B12 deficiency have a distinctive profile of cognitive impairment different from the episodic memory deficit usually observed in MCI. RESULTS: From a cohort of 310 patients with MCI followed in a memory clinic in Lisbon, only 10 cases with vitamin B12 deficiency were found. From collaboration with other neurologists, 5 further patients with vitamin B12 deficiency were added. These cases were compared to MCI patients with normal vitamin B12 levels in a ratio 1:3. The duration of subjective cognitive symptoms was significantly shorter in MCI patients with B12 deficiency (1.2±1.0 years) as compared to MCI patients with normal vitamin B12 levels (3.4±3.0 years, p<0.001, Student' t test). There were no statistically significant differences in the neuropsychological tests between MCI patients with and without vitamin B12 deficiency. Vitamin B12 was started in MCI patients with vitamin B12 deficiency, with no noticeable clinical improvement. CONCLUSION: MCI patients with low levels of vitamin B12 had no particular profile of cognitive impairment, however vitamin B12 deficiency might have precipitated the onset of symptoms. The effect of vitamin B12 supplementation in patients with MCI and low vitamin B12 levels should be clarified by future prospective studies.