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Background: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data., Method: The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized., Results: This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau., Conclusions: Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.

Objective: The purpose of this study was to investigate the neuropathological substrates underlying in vivo hippocampal atrophy on magnetic resonance imaging (MRI) in autopsy confirmed neurodegenerative dementia cases., Methods: Thirty-one neuropathologically verified cases (23 with Lewy body dementia (LBD) and eight with Alzheimer's disease (AD)) were included who had undergone an MRI scan close to death (mean 1.5 years). Manual volumetric measurements were undertaken for the hippocampus, entorhinal cortex and amygdala on MRI, along with quantitative neuropathological analysis of plaque, tangle and Lewy body pathology in the same regions. The relationship between neuropathology and MRI volumes was assessed using correlations and linear regression., Results: Hippocampal and amygdala volumes were significantly smaller in cases with AD than with LBD, but there was no difference in entorhinal cortex volume. Analysing all cases together, a significant positive correlation was observed between normalised hippocampal volume and percent area of Lewy bodies in the hippocampus (r=0.449, p=0.017) but not with tangles (r=0.059, p=0.766) or plaques (r=-0.361, p=0.119). There were no other significant correlations between regional MRI volume and measures of neuropathology. Regression analysis showed that overall diagnosis of AD rather than burden of individual pathological changes was the most significant predictor of hippocampal volume loss in autopsy confirmed cases., Conclusion: Our results suggest that (i) hippocampal and amygdala but not entorhinal cortex, volumes differ between AD and LBD and (ii) factors other than current markers of neurodegenerative pathological change are responsible for atrophy of medial temporal lobe structures in AD and LBD., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Acetyl Cholinesterase Inhibitors (AChEIs) have been in clinical use for the past five years in the UK for the symptomatic treatment of Alzheimer's disease (AD). There are few data on the patterns and predictors of response to AChEI therapy in routine clinical practice. We therefore investigated clinical variables that may distinguish between AChEI responders and non-responders., Methods: A retrospective sample of 160 consecutive patients with dementia who were treated on clinical grounds with an AChEI was studied. Treatment response was defined in two ways: (a) A clinical response was achieved when there was no deterioration or there was an improvement on a global clinical assessment (CGI) and (b) a Mini-Mental-State-Examination (MMSE) response when there was an improvement of 2 or more MMSE points., Results: A total of 62 (45%) patients achieved an MMSE response. A diagnosis of dementia with Lewy Bodies (DLB) and Parkinson's disease+Dementia (PDD) was associated with a MMSE response, as were hallucinations, and lower MMSE scores at baseline. 125 (78%) patients achieved a CGI response for which there were no clinical predictors., Conclusions: Severity of illness, a diagnosis of DLB and PDD, and presence of hallucinations at baseline were predictive of a MMSE response. Non-AD dementia and severe dementia responded equally well to AChEI treatment and results of further randomised, placebo-controlled studies are needed to clarify the role of AChEI in the treatment of these disorders., (Copyright 2003 John Wiley & Sons, Ltd.)

The neuropathological staging model proposed by Braak and Braak (1991) implies that the evolution of neurofibrillary pathology follows a predictable sequence and can be ordered in a regular regional hierarchy. A total of 42 cases of an elderly population sample, which had been prospectively clinically assessed, were examined. Clinical diagnosis was made according to the CAMDEX criteria, and the sample reported here did not include cases were vascular dementia according to the criteria proposed by Chui et al. (1991). The neuropathological staging procedure was applied as originally proposed by Braak and Braak (1991). In addition, in all cortical laminae and regions which are essential for the staging model neurofibrillary tangles were quantified. Demented cases had significantly more areas involved and more advanced neuropathological stages. Cases with stages 1-3 tended to be non-demented, and cases with stages 4-6 tended to be demented. However, there was a considerable degree of overlap and no clear-cut threshold could be established. This brings into question the diagnostic value of the staging model.

Objectives: Depression in older people is commonly under diagnosed and is associated with increased morbidity and mortality. Because older people currently occupy 65% of acute hospital beds, it is crucial for them to be properly assessed for depression to optimise their medical care. The aim of this study was to identify potential risk factors for depression in the medically ill in order to improve their inpatient care.Methods: This was a 2-year observational study of consequent referrals to the Newcastle Liaison Team for Older Adults. Out of a total number of 1586 referred patients, 1197 were included in the final analysis of data. Information about their age, main medical history, cognitive impairment and use of antidepressants was collected. All subjects were screened for dementia, depression and delirium. Proportions were compared using the chi-squared test. Clinical depression as a binary variable was modelled using logistic regression.Results: Higher risk for depression was associated with pain (odds ratio (OR) = 1.76; p = 0.033) and a previous history of depression (OR = 2.22; p < 0.001). Cognitive impairment (OR = 0.44, p < 0.001) and delirium (OR = 0.49; p < 0.001) decreased the likelihood for having depression. Subjective feelings of emptiness, being unhappy and depressed alone (R2  = 37.4%) and cognitive impairment (R2  = 39.5%) were the best multivariable model to explain depression in medically ill people.Conclusion: Dysphoric mood results in depression in older people with medical health problems. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors occurring in subjects with dementia. BPSD constitute a major component of the dementia syndrome irrespective of its subtype. They are as clinically relevant as cognitive symptoms as they strongly correlate with the degree of functional and cognitive impairment. BPSD include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite changes. It is estimated that BPSD affect up to 90% of all dementia subjects over the course of their illness, and is independently associated with poor outcomes, including distress among patients and caregivers, long-term hospitalization, misuse of medication, and increased health care costs. Although these symptoms can be present individually it is more common that various psychopathological features co-occur simultaneously in the same patient. Thus, categorization of BPSD in clusters taking into account their natural course, prognosis, and treatment response may be useful in the clinical practice. The pathogenesis of BPSD has not been clearly delineated but it is probably the result of a complex interplay of psychological, social, and biological factors. Recent studies have emphasized the role of neurochemical, neuropathological, and genetic factors underlying the clinical manifestations of BPSD. A high degree of clinical expertise is crucial to appropriately recognize and manage the neuropsychiatric symptoms in a patient with dementia. Combination of non-pharmacological and careful use of pharmacological interventions is the recommended therapeutic for managing BPSD. Given the modest efficacy of current strategies, there is an urgent need to identify novel pharmacological targets and develop new non-pharmacological approaches to improve the adverse outcomes associated with BPSD. [ABSTRACT FROM AUTHOR]