The neurocognitive disorder cohort RIFADE: Aims, methods, first results showing cognitive improvement in a subgroup.

BACKGROUND: The NCD cohort study RIFADE (RIsk FActors of DEmentia) investigates the interaction of risk factors and neurocognitive disorders (NCDs) due to Alzheimer's disease (NCD-AD) and NCD of vascular type (NCD-vascular). Retrospective recruitment referred to a period from 2007 to 2018 in a single centre. In addition to the baseline visit, follow-up visits took place at 3, 6, 12 months followed by yearly visits. Visit times varied in part depending on adherence. The study also comprises an EEG bank and a bank with cerebral MRI (c-MRI). METHODS: Inclusion criteria were broad in order to cover a wide range of patterns of NCD. At baseline, patients underwent a large panel of assessments, e.g. including clinical history, diagnostic evaluation for NCD according to DSM-IV and NINDS AIREN criteria, a cognitive test battery including the DemTect, the clock drawing test and the Instrumental-Activities-of-Daily-Living-scale of Lawton and Brodie, EEG and c-MRI. At each follow-up visit, cognitive tests were repeated, in most cases also EEGs and in some cases c-MRIs. Numerous risk factors (RF) including vascular RF, atrial fibrillation, heart failure, sleep apnoea and lifestyle factors such as sedentary lifestyle, low cognitive style and smoking were evaluated for presence and for correction status at each visit, and modulation of uncorrected RF was initiated. RESULTS: Overall, 126 subjects with a clinical diagnosis of NCD were included (52% female, mean age 71 ± 10.6 years (range 35e86)), number of follow-up visits per subject 2.9 ± 2.4, observation time per subject 3.4 ± 2.8 years). Of these, 55/28/17% presented with the clinical stages subjective cognitive decline (SCD)/mild cognitive impairment (MCI)/dementia (major NCD). Clinical diagnoses, retrospectively re-evaluated according to DSM-5, were 5/21/68/6% Alzheimer´s disease (NCD-AD)/vascular NCD (NCD-vascular) / mixed NCD (NCD-AD + NCD-vascular)/unspecified NCD. First longitudinal results revealed a mean DemTect score at baseline 12.6 ± 4.2 vs last visit 12.0 ± 4.8 (p = 0.08) and a clock drawing test score at baseline 1.9 ± 1.3 vs last visit 2.3 ± 1.5 (p < 0.0001). Of all subjects with MCI or major NCD (n = 57), 19 improved in the clinical stage from baseline to last visit (33.3%). Sixteen subjects progressed from SCD or MCI (n = 104) to major NCD (15.4%). CONCLUSION: The German NCD cohort RIFADE comprises patients with all clinical stages of NCD. A considerable subgroup improved in clinical stage. Further analysis is needed to answer the question of whether modulation of multiple risk factors provides a favourable effect on cognitive outcome in NCD.

Normal Pressure Hydrocephalus Associated with Alzheimer's Disease.

OBJECTIVE: The aim was to investigate whether neurodegenerative biomarkers in cerebrospinal fluid (CSF) differentiate patients with suspected normal pressure hydrocephalus (NPH) who respond to CSF drainage from patients who do not respond. METHODS: Data from 62 consecutive patients who presented with magnetic resonance imaging changes indicative of NPH were studied with regard to cognitive and gait functions before and after drainage of 40-50ml of CSF. Additionally, S100 protein, neuron-specific enolase, ß-amyloid protein, tau protein and phospho-tau were determined in CSF. Statistical analyses were carried out with ANOVA and multiple linear regression. RESULTS: Patients with CSF constellations typical for Alzheimer's disease (n = 28) improved significantly in cognitive and gait-related functions after CSF drainage. In contrast, those patients without a CSF constellation typical for Alzheimer's disease (n = 34) did not improve in cognitive and gait-related functions after CSF drainage. In addition, positive CSF biomarkers for Alzheimer's disease predicted these improvements. INTERPRETATION: Our data suggest an association between Alzheimer's disease and NPH changes, supporting the recently suggested dichotomy of a neurodegenerative NPH and a true idiopathic NPH, with the latter appearing to be rare. ANN NEUROL 2020;88:703-711.

Treatment of hypertension and obstructive sleep apnea counteracts cognitive decline in common neurocognitive disorders in diagnosis-related patterns.

The aim of this study was to investigate the effect of arterial hypertension (AH) and of obstructive sleep apnea (OSA) on cognitive course in the neurocognitive disorder (NCD) cohort RIFADE which enrolled patients with NCD due to Alzheimer's disease (AD), vascular NCD (vNCD), and mixed NCD (AD + vNCD = mNCD). Multiple risk factors (RF), including AH and OSA, that contribute to the development of various kinds of dementia have been identified in previous studies. Studies that observed AH lacked investigation of long-term effects and did not isolate it from other RF. Studies involving OSA as a risk factor did not include participants with all stages of NCD. 126 subjects were screened for AH and OSA. Repeated cognitive measurements were performed with the DemTect as primary outcome and the clock drawing test as secondary outcome measure. 90 patients had AH (71.4%) and 40 patients had OSA (31.7%). RF-status had a significant effect on cognitive outcome in models with RF as single factors (AH p = 0.027, OSA p < 0.001), a 2-factor analysis with AH × OSA (AH as main factor p = 0.027) as well as a model including the 3 factors AH × OSA × diagnosis (p = 0.038). Similarly, a 3-factor model was significant for the clock-drawing test, whereas single factor-models remained insignificant. AH and OSA appear to be risk factors in common NCD and cognitive decline can be mitigated by treatment of these RF.