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Background. Alzheimer’s disease (AD) pathology and vascular burden are highly prevalent and often co-occur in elderly, but it remains unclear how both are associated with cognitive decline. We aimed to investigate whether amyloid abnormality and vascular burden synergistically contribute to cognitive decline in a memory clinic population. Methods. In this longitudinal study, 228 participants across the clinical AD spectrum (SCD, MCI, dementia) were included from Maastricht and Aachen university memory clinics. Amyloid abnormality (A) was measured by cerebrospinal fluid (CSF) Aβ-42, using data-driven cut-offs. Vascular burden (V) was defined as having either moderate to severe white matter lesions (Fazekas score ≥ 2), one or more microbleeds, intracranial hemorrhage or infarcts on MRI. Participants were divided into four groups: A-V-, A-V+, A + V-, and A + V+. Outcome measures were global cognition, memory, processing speed, executive functioning, and language z-scores. Linear mixed models were used, adjusted for age, sex, education, with center as random factor. Effects of individual MRI vascular measures and Aβ-42 abnormality on cognitive decline were also assessed. In secondary analyses, presence of vascular risk factors and disease were used as V definitions. Results. At baseline, the A + V + group scored worse on global cognition and language compared to all other groups. The A + V + group also had worse memory scores compared to A-V + and A-V- groups. Over time, with an average follow-up of 2.7 years (SD = 1.5), the A + V + and A + V- groups showed faster decline in global cognition than the A-V + and A-V- groups. Only the A + V- group showed decline on memory and language scores. The A-V + group did not differ from the A-V- group in any domain. Findings were similar in persons without dementia and when vascular risk factors and disease were used as V definitions. When assessing MRI vascular measures individually, no synergistic effects on cognitive decline were shown and only microbleeds were independently associated with executive functioning decline over time. Conclusions. Our study shows that amyloid abnormality predicts cognitive decline in a memory clinic population independent from vascular burden. Vascular burden has a minor contribution to cognitive decline in these patients. This has implications for prognostic procedures in memory clinic patients.

Contains fulltext : 287461.pdf (Publisher’s version ) (Open Access) Clinical and genomic studies have shown an overlap between neuropsychiatric disorders and insulin resistance (IR)-related somatic conditions, including obesity, type 2 diabetes, and cardiovascular diseases. Impaired cognition is often observed among neuropsychiatric disorders, where multiple cognitive domains may be affected. In this review, we aimed to summarise previous evidence on the relationship between IR-related diseases/traits and cognitive performance in the large UK Biobank study cohort. Electronic searches were conducted on PubMed, Scopus, and Web of Science until April 2022. Eighteen articles met the inclusion criteria and were qualitatively reviewed. Overall, there is substantial evidence for an association between IR-related cardio-metabolic diseases/traits and worse performance on various cognitive domains, which is largely independent of possible confoundings. The most consistent findings referred to IR-related associations with poorer verbal and numerical reasoning ability, as well as slower processing speed. The observed associations might be mediated by alterations in immune-inflammation, brain integrity/connectivity, and/or comorbid somatic or psychiatric diseases/traits. Our findings provide impetus for further research into the underlying neurobiology and possible new therapeutic targets.

BACKGROUND: The relation between vascular risk factors (VRFs) and Alzheimer's disease (AD) is important due to possible pathophysiological association.OBJECTIVE: To assess the prevalence of VRFs in biomarker-based AT(N) groups and the associations between VRFs, AD cerebrospinal fluid (CSF) biomarkers, brain magnetic resonance imaging (MRI), and cognition in clinical context.METHODS: We included patients from two memory clinics in University Hospital Aachen (Germany) and Maastricht University Medical Centre (The Netherlands). Subjects were older than 45 years and had available data on demographics, VRFs, CSF AD biomarkers, and MRI. We categorized individuals in normal AD biomarkers, non-AD change, and AD-continuum groups based on amyloid (A), tau (T), and neurodegeneration (N) status in CSF and MRI. Regression models were corrected for age, sex, and site.RESULTS: We included 838 participants (mean age 68.7, 53.2% male, mean MMSE 24.9). The most common VRFs were smoking (60.9%), hypertension (54.6%), and dyslipidemia (37.8%). Alcohol abuse and smoking were most frequent in the non-AD-change group, and coronary heart disease and carotid artery stenosis in the AD continuum group. Higher rates of depression were found in the normal AD biomarkers group. Parietal atrophy and cortical microbleeds were specific for the AD continuum group. Carotid artery stenosis was associated with pathological Aβ 42 and T-tau values, and diabetes and alcohol abuse were associated with worse medial temporal atrophy and atrial fibrillation, with worse cognition.CONCLUSION: VRFs are common in memory clinic patients, showing differences across the AT(N) biomarker groups. This is important for prevention and individualized treatment of dementia.

Background and AimsSleep is important for consolidation of motor learning, but brain injury may affect sleep continuity and therefore rehabilitation outcomes. This study aims to assess the relationship between sleep quality and motor recovery in brain injury patients receiving inpatient rehabilitation.Methods59 patients with brain injury were recruited from two specialist inpatient rehabilitation units. Sleep quality was assessed (up to 3 times) objectively using actigraphy (7 nights) and subjectively using the Sleep Condition Indicator. Motor outcome assessments included: Action Research Arm test (upper limb function), Fugl Meyer assessment (motor impairment) and the Rivermead Mobility Index. The functional independence measure (FIM) was assessed at admission and discharge by the clinical team. 55 age and gender matched healthy controls completed one assessment.ResultsInpatients demonstrated lower self-reported sleep quality (p2adj = 0.12, p = 0.03), whereby more disrupted sleep was associated with slower recovery.ConclusionsInpatients with brain injury demonstrate impaired sleep quality, and this is associated with poorer motor outcomes and slower functional recovery. Further investigation is needed to determine how sleep quality can be improved and whether this affects outcome.