Objectives
To study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia.
Methods
Risk of dementia in ...men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer‐free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non‐Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW.
Results
A total of 25 967 men with prostate cancer and 121 018 prostate cancer‐free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin‐releasing hormone agonist treatment ( HR 1.15, 95% confidence interval CI 1.07–1.23) and orchiectomy (HR 1.60, 95% CI 1.32–1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer‐free men; however, this increase in risk was only observed for non‐Alzheimer's dementia and occurred from year 1–4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW.
Conclusion
This population‐based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non‐Alzheimer's dementia.
•Structural brain imaging using CT or MRI should be included in a dementia investigation.•There are differences between CT and MRI in price, availability and comfort for the patient.•CT is ...diagnostically equivalent and more cost effective than MRI.•The diagnostic added value of MRI does not justify the recommendation of MRI rather than CT.
The demands for more people to be investigated due to cognitive failure and suspected dementia are increasing as increasing numbers of us get older and the incidence of dementia increases. An important part of a dementia study includes the structural imaging of the brain. Two imaging techniques, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), are used in this context. They differ in many ways and one question is which of the methods should be used in the first instance. Considering the large number of investigations to be expected in the future it is vital that they be cost-effective. Structural imaging aims partly to find secondary causes of cognitive failure and partly to provide support in the differential diagnostic reasoning. The methods differ; CT is significantly cheaper but exposes the patient to radiation, MRI is expensive but does not use X-rays. MRI provides better imaging of cerebrovascular lesions than CT as well as better imaging of structures near the skull base. The difference in diagnostic accuracy is small and it is doubtful whether that difference justifies the large difference in cost.
Atrophy patterns on MRI can reliably predict three neuropathological subtypes of Alzheimer's disease (AD): typical, limbic-predominant, or hippocampal-sparing. A method to enable their investigation ...in the clinical routine is still lacking. We aimed to (1) validate the combined use of visual rating scales for identification of AD subtypes; (2) characterise these subtypes at baseline and over two years; and (3) investigate how atrophy patterns and non-memory cognitive domains contribute to memory impairment. AD patients were classified as either typical AD (n = 100), limbic-predominant (n = 33), or hippocampal-sparing (n = 35) by using the Scheltens' scale for medial temporal lobe atrophy (MTA), the Koedam's scale for posterior atrophy (PA), and the Pasquier's global cortical atrophy scale for frontal atrophy (GCA-F). A fourth group with no atrophy was also identified (n = 30). 230 healthy controls were also included. There was great overlap among subtypes in demographic, clinical, and cognitive variables. Memory performance was more dependent on non-memory cognitive functions in hippocampal-sparing and the no atrophy group. Hippocampal-sparing and the no atrophy group showed less aggressive disease progression. Visual rating scales can be used to identify distinct AD subtypes. Recognizing AD heterogeneity is important and visual rating scales may facilitate investigation of AD heterogeneity in clinical routine.
The human resting-state is characterized by spatially coherent brain activity at a low temporal frequency. The default mode network (DMN), one of so-called resting-state networks, has been associated ...with cognitive processes that are directed toward the self, such as introspection and autobiographic memory. The DMN's integrity appears to be crucial for mental health. For example, patients with Alzheimer's disease or other psychiatric conditions show disruptions of functional connectivity within the brain regions of the DMN. However, in prodromal or early stages of Alzheimer's disease, physiological alterations are sometimes elusive, despite manifested cognitive impairment. While functional connectivity assesses the signal correlation between brain areas, multi-scale entropy (MSE) measures the complexity of the blood-oxygen level dependent signal within an area and thus might show local changes before connectivity is affected. Hence, we investigated alterations of functional connectivity and MSE within the DMN in fifteen mild Alzheimer's disease patients as compared to fourteen controls. Potential associations of MSE with functional connectivity and cognitive abilities i.e., mini-mental state examination (MMSE) were assessed. A moderate decrease of DMN functional connectivity between posterior cingulate cortex and right hippocampus in Alzheimer's disease was found, whereas no differences were evident for whole-network functional connectivity. In contrast, the Alzheimer's disease group yielded lower global DMN-MSE than the control group. The most pronounced regional effects were localized in left and right hippocampi, and this was true for most scales. Moreover, MSE significantly correlated with functional connectivity, and DMN-MSE correlated positively with the MMSE in Alzheimer's disease. Most interestingly, the right hippocampal MSE was positively associated with semantic memory performance. Thus, our results suggested that cognitive decline in Alzheimer's disease is reflected by decreased signal complexity in DMN nodes, which might further lead to disrupted DMN functional connectivity. Additionally, altered entropy in Alzheimer's disease found in the majority of the scales indicated a disturbance of both local information processing and information transfer between distal areas. Conclusively, a loss of nodal signal complexity potentially impairs synchronization across nodes and thus preempts functional connectivity changes. MSE presents a putative functional marker for cognitive decline that might be more sensitive than functional connectivity alone.
There is an urgent need for Alzheimer's disease (AD) biomarkers—especially in the context of clinical trials. Biomarkers for early diagnosis, disease progression, and prediction are most critical, ...and disease‐modification therapy development may depend on the discovery and validation of such markers. AddNeuroMed is a cross European, public/private consortium developed for AD biomarker discovery. We report here the development and design of AddNeuroMed and the progress toward the development of plasma markers. Despite the obstacles to such markers, we have identified a range of markers including CFH and A2M, both of which have been independently replicated. The experience of AddNeuroMed leads us to three overall conclusions. First, collaboration is essential. Second, design is paramount and combining modalities, such as imaging and proteomics, may be informative. Third, animal models are valuable in biomarker research. Most importantly, we have learned that plasma markers are feasible.
Background
Cognitive impairment is common among older people and is associated with increased morbidity and mortality. The main aim of this study was to evaluate the validity of the Persian version ...of the Abbreviated Mental Test Score (AMTS) as a screening tool for dementia.
Methods
Data were obtained from a cross‐sectional study. One hundred and one older adults who were members of Iranian Alzheimer Association and 101 of their siblings were entered into this study by convenient sampling. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for diagnosing dementia and the Mini‐Mental State Examination were used as the study tools. The gathered data were analyzed by the Mann–Whitney U‐test, the Kruskal–Wallis test, Spearman's rank correlation coefficient, and the receiver–operating characteristic.
Results
The AMTS could successfully differentiate the dementia group from the non‐dementia group. Scores were significantly correlated with Diagnostic and Statistical Manual of Mental Disorders diagnosis for dementia and Mini‐Mental State Examination scores (P < 0.001). Educational level (P < 0.001) and male sex (P = 0.015) were positively associated with AMTS, whereas (P < 0.001) was negatively associated with AMTS. Total Cronbach's α coefficient was 0.90. The scores 6 and 7 showed the optimum balance between sensitivity (99% and 94%, respectively) and specificity (85% and 86%, respectively).
Conclusions
The Persian version of the AMTS is a valid cognitive assessment tool for older Iranian adults and can be used for dementia screening in Iran.
Understanding Alzheimer's disease (AD) heterogeneity is important for understanding the underlying pathophysiological mechanisms of AD. However, AD atrophy subtypes may reflect different disease ...stages or biologically distinct subtypes. Here we use longitudinal magnetic resonance imaging data (891 participants with AD dementia, 305 healthy control participants) from four international cohorts, and longitudinal clustering to estimate differential atrophy trajectories from the age of clinical disease onset. Our findings (in amyloid-β positive AD patients) show five distinct longitudinal patterns of atrophy with different demographical and cognitive characteristics. Some previously reported atrophy subtypes may reflect disease stages rather than distinct subtypes. The heterogeneity in atrophy rates and cognitive decline within the five longitudinal atrophy patterns, potentially expresses a complex combination of protective/risk factors and concomitant non-AD pathologies. By alternating between the cross-sectional and longitudinal understanding of AD subtypes these analyses may allow better understanding of disease heterogeneity.
We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and ...neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß1-42, total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD.
PDF
