Mild Cognitive Impairment is not a Valid Concept and Should be Replaced by a More Restrictive, Biologically Validated Class, Named Mild Cognitive Dysfunctions (MCD): A Nomothetic Network Approach

Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD.Conclusions: Petersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.

Mild cognitive impairment is not a valid concept and should be replaced by a more restrictive, biologically validated class, named Mild Cognitive Dysfunctions (MCD): a nomothetic network approach.

Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2 % of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD. Conclusions: Petersen s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.

Is a One Welfare Approach the Key to Addressing Unintended Harms and Maximising Benefits Associated with Animal Shelters?

Animal shelters, pounds and rescue organisations have evolved over time. Today they serve three purposes: to reduce animal welfare harms, to reduce harms to the community associated with free-roaming, stray or unwanted companion animals, and to reduce their associated environmental harms. This discussion explores the evolution of animal shelters, and argues that they are justified on utilitarian grounds. It explores unintended harms of shelters on animal welfare, including humane killing for the purposes of population control and shelter population management, as well as risks associated with confinement including behavioural deterioration and infectious diseases. It also explores harms to non-human animals, including moral distress and compassion fatigue. Finally, it explores potential environmental harms of shelters. The One Welfare concept, utilised in the World Animal Health Organisation (OIE) Global Animal Welfare Strategy, acknowledges the interplay between animal welfare, human well-being and environmental sustainability. It is argued that the One Welfare framework is critical in minimising harms and maximising benefits associated with animal shelters.

Correlates of Positive and Negative Schizophrenic Syndromes in Nigerian Patients

The two-syndrome concept of schizophrenia was investigated in a sample of 70 Nigerian schizophrenic patients. The positive and negative syndromes were studied in relation to demographic, historical, neurological and psychometric measures. The negative syndrome was associated with cognitive impairment, behavioural deterioration and left eye dominance, and also with poor pre-morbid educational achievement and longer length of current stay in hospital. The positive syndrome was unrelated to any of the independent variables. The two syndromes were not significantly related, supporting the view that they represent relatively independent dimensions of pathology. This provides further support for the validity of the Type I–Type II subtyping of schizophrenia in populations of patients from different cultural backgrounds, and suggests that the negative syndrome is related to the presence of neurodevelopmental deficits that possibly antedate the schizophrenic illness.

Correlates of Positive and Negative Schizophrenic Syndromes in Nigerian Patients

The two-syndrome concept of schizophrenia was investigated in a sample of 70 Nigerian schizophrenic patients. The positive and negative syndromes were studied in relation to demographic, historical, neurological and psychometric measures. The negative syndrome was associated with cognitive impairment, behavioural deterioration and left eye dominance, and also with poor pre-morbid educational achievement and longer length of current stay in hospital. The positive syndrome was unrelated to any of the independent variables. The two syndromes were not significantly related, supporting the view that they represent relatively independent dimensions of pathology. This provides further support for the validity of the Type I–Type II subtyping of schizophrenia in populations of patients from different cultural backgrounds, and suggests that the negative syndrome is related to the presence of neurodevelopmental deficits that possibly antedate the schizophrenic illness.

Major Depression in Down's Syndrome

Five patients with trisomy 21 (Down's syndrome (DS)), referred to us for evaluation of dementia, were instead found to have major depression. All had shown cognitive and behavioural deterioration and this had led to a mistaken diagnosis of Alzheimer's disease in two. We outline and contrast the features of major depression and Alzheimer's disease in DS, and suggest that electroconvulsive therapy is an effective treatment for major depression in DS.