Efficacy of Vitamin C Treatment to Aid the Healing of Foot Ulcers in People With Diabetes: A Randomised, Placebo-Controlled Double-Blind Trial: The FOOT-C Study Protocol.

Diagnosis of memory clinic patients, particularly AD patients, has dramatically improved over the last decades, which is mainly due to biomarker developments. However, disease-defining imaging or liquid biomarkers of disease pathology (e.g., PET or cerebrospinal fluid) are not widely available, and clinical diagnosis alone is often incorrect, even in specialized settings []. Still, when counseling of patients and relatives addresses the prognosis, e.g., estimation of survival duration, this is often based on the clinically assumed diagnosis. Neuropsychological assessment is recommended in dementia diagnostic criteria and is hence standard in memory clinics to aid the diagnostic decision. Scores from neuropsychological tests reflect (regional) brain health and disease severity. Thus, neuropsychological test scores might bear the potential to more directly infer estimates of survival duration/mortality risk than coarse diagnostic categories. A commonly applied test battery is the neuropsychological assessment battery of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-NAB) [], which includes tests of memory, but also semantic fluency. Interestingly, one previous study showed that semantic fluency predicts survival in clinically diagnosed AD []. However, due to a lack of biomarker-confirmation of the clinical AD diagnosis, it is not clear whether the patient sample contained patients with neurodegenerative diseases other than AD, e.g., limbic-predominant age-related TDP-43 encephalopathy (LATE) or frontotemporal lobar degeneration (FTLD). Particularly the presence of FTLD patients in the patient sample might have biased the survival outcome on one side [, ] and assessment of semantic fluency on the other []. Intriguingly, in a very recent study Ghisletta et al. [] demonstrated that semantic fluency predicts survival also in healthy elderly individuals. The previous studies that demonstrated the predictive value of semantic fluency alone [] or semantic fluency combined with phonemic fluency [] used different, large sets of neuropsychological tests covering a wide range of cognitive domains (Cosentino et al.,: verbal fluency, memory, abstract reasoning, visuospatial functioning, and language; Ghisletta et al.: verbal fluency, perceptual speed, episodic memory, verbal knowledge, and general intelligence). Importantly, among all these domains and tasks, both identified semantic fluency alone [] or in a combined score with phonemic fluency [] as the best predictors of survival. Impaired semantic fluency may reflect disruption of frontotemporal networks supporting semantic retrieval and executive search processes []. Frontal lobe dysfunction may, on one end of the spectrum, promote risk-taking behavior and poor medication adherence, or, conversely, lead to apathy and diminished self-initiated activity []. The latter may adversely affect musculoskeletal and cardiovascular health through prolonged immobility or bed rest [, ]. Both behavioral extremes may ultimately contribute to an increased risk of mortality.