Irreversible Dementia Research Articles

Development of SPECT Probes for In Vivo Imaging of β-Amyloid and Tau Aggregates in the Alzheimer's Disease Brain

Alzheimer's disease (AD) is the most common form of irreversible dementia among elderly people. In the postmortem brains of AD patients, the deposition of senile plaques composed of β-amyloid (Aβ) peptides and neurofibrillary tangles composed of highly phosphorylated tau proteins are two neuropathological hallmarks. Therefore, the in vivo imaging of Aβ and tau aggregates with positron-emission tomography (PET) or single-photon emission computed tomography (SPECT) would promote drug development, early diagnosis, and monitoring of the disease status in AD patients. In this study, we designed and synthesized novel Aβ and tau imaging probes for SPECT. [125I]PBOX-3, developed as an Aβ imaging probe, showed high affinity for Aβ aggregates in vitro. A SPECT/CT study with [123I]PBOX-3 revealed a higher level of radioactivity in a Tg2576 mouse, which is the AD model mouse, than in a wild-type mouse. In addition, ex vivo autoradiograms of brain sections from a Tg2576 mouse after the injection of [123I]PBOX-3 showed the selective binding of Aβ plaques. BIP-NMe2, developed as a tau imaging probe, showed high and selective affinity for tau aggregates in AD brain sections. In addition, [125I]BIP-NMe2 displayed high initial uptake into, and fast washout from, the normal mouse brain, suggesting that [125I]BIP-NMe2 has favorable pharmacokinetics for the in vivo imaging of tau aggregates. Taken together, we successfully developed an Aβ imaging probe, PBOX-3, and a tau imaging probe, BIP-NMe2. These probes may be used to develop novel methods for the diagnosis, treatment and monitoring of AD progression.

Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

Early Signs of Pathological Cognitive Aging in Mice Lacking High-Affinity Nicotinic Receptors.

In order to address pathological cognitive decline effectively, it is critical to adopt early preventive measures in individuals considered at risk. It is therefore essential to develop approaches that identify such individuals before the onset of irreversible dementia. A deficient cholinergic system has been consistently implicated as one of the main factors associated with a heightened vulnerability to the aging process. In the present study we used mice lacking high affinity nicotinic receptors (β2-/-), which have been proposed as an animal model of accelerated/premature cognitive aging. Our aim was to identify behavioral signs that could serve as indicators or predictors of impending cognitive decline. We used test batteries in order to assess cognitive functions and additional tasks to investigate spontaneous behaviors, such as species-specific activities and exploration/locomotion in a novel environment. Our data confirm the hypothesis that β2-/- animals exhibit age-related cognitive impairments in spatial learning. In addition, they document age-related deficits in other areas, such as recognition memory, burrowing and nesting building, thereby extending the validity of this animal model for the study of pathological aging. Finally, our data reveal deficits in spontaneous behavior and habituation processes that precede the onset of cognitive decline and could therefore be useful as a non-invasive behavioral screen for identifying animals at risk. To our knowledge, this is the first study to perform an extensive behavioral assessment of an animal model of premature cognitive aging, and our results suggest that β2-nAChR dependent cognitive deterioration progressively evolves from initial subtle behavioral changes to global dementia due to the combined effect of the neuropathology and aging.

Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease.

Adenosine to inosine (A-to-I) RNA editing, catalyzed by the ADAR enzyme family, acts on dsRNA structures within pre-mRNA molecules. Editing of the coding part of the mRNA may lead to recoding, amino acid substitution in the resulting protein, possibly modifying its biochemical and biophysical properties. Altered RNA editing patterns have been observed in various neurological pathologies. Here, we present a comprehensive study of recoding by RNA editing in Alzheimer's disease (AD), the most common cause of irreversible dementia. We have used a targeted resequencing approach supplemented by a microfluidic-based high-throughput PCR coupled with next-generation sequencing to accurately quantify A-to-I RNA editing levels in a preselected set of target sites, mostly located within the coding sequence of synaptic genes. Overall, editing levels decreased in AD patients’ brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. Differential RNA editing levels were observed in 35 target sites within 22 genes. These results may shed light on a possible association between the neurodegenerative processes typical for AD and deficient RNA editing.

Brain Capillaries in Alzheimer’s Disease

Alzheimer's disease is the most common cause of irreversible dementia, affecting mostly the presenile and senile age, shaping a tragic profile in the epilogue of the life of the suffering people. Due to the severity and the social impact of the disease an ongoing research activity is in climax nowadays, associated with many legal, social, ethical, humanitarian, philosophical and economic considerations. From the neuropathological point of view the disease is characterized by dendritic pathology, loss of synapses and dendritic spines, affecting mostly selective neuronal networks of critical importance for memory and cognition, such as the basal forebrain cholinergic system, the medial temporal regions, the hippocampus and many neocortical association areas. Tau pathology consisted of intracellular accumulation of neurofibrillary tangles of hyperphosphorilated tau protein and accumulation of Aβ-peptide's deposits, defined as neuritic plaques, are the principal neuropathological diagnostic criteria of the disease. The neurotoxic properties of the oligomerics of the Aβ-peptide and tau mediated neurodegeneration are among the main causative factors of impaired synaptic plasticity, neuronal loss, dendritic alterations and tremendous synaptic loss. The gradual degeneration of the organelles, particularly mitochondria, smooth endoplasmic reticulum and Golgi apparatus, visualized clearly by electron microscopy (EM), emphasize the importance of the oxidative stress and amyloid toxicity in the pathogenetic cascade of the disease. The vascular factor may be an important component of the whole spectrum of the pathogenesis of AD. It is of substantial importance the concept that the structural alterations of the brain capillaries, may contribute in the pathology of AD, given that the disruption of the BBB may induce exacerbation of AD pathology, by promoting inflammation around the blood capillaries and in the neuropile space diffusely. From the morphological point of view, silver impregnation techniques revealed a marked tortuosity of the capillaries in early cases of AD. In addition, the distance between two branch points is longer in capillaries of AD brains, whereas the branch point density as well as the ratio of the branch point density to astrocytic density is substantially decreased in AD in comparison with age matched normal controls. EM revealed, that the most frequent morphological alterations of the brain capillaries in AD consist of thickness, splitting and duplication of the basement membrane, reduction of the length of tight junctions, decrease of the number of tight junctions per vessel length, associated as a rule, with morphological alterations of the mitochondria of the endothelial cells, the pericytes and the perivascular astrocytic processes. The number of the pinocytotic vesicles is substantially increase in the endothelium of the brain capillaries in AD in comparison with age matched normal controls. Endothelial cells play a very important role in the transport systems in the brain. Subsequently, the dysfunction of the endothelial cells and the disruption of the BBB may induce serious impairment in the transport system. The dysfunction of the brain capillaries may result in releasing neurotoxic factors, such as thrombin, pro-inflammatory cytokines, nitric oxide and leukocyte adhesion molecules, and in abnormal regulation of Aβ-peptide homeostasis in the brain. The impairment of the brain capillaries in structures of the brain, which are crucial for the homeostatic equilibrium, such as the hypothalamic nuclei, may induce autonomic dysfunction, which usually occur in the advanced stages of AD, affecting dramatically the viability of the patients. Degeneration of the pericytes is also observed emphasizing even more the importance of the vascular factor in AD. Pericytes may serve as integrators, coordinators and effectors of blood-brain barrier structure and maintenance, and play a key role in microvascular stability, capillary density and angiogenesis. The correlation between AD pathology and vascular pathology, at the level of brain capillaries and BBB, raises the rational question, whether the efficient treatment of the vascular factor might be beneficial for the patients who suffer from AD. It is reasonable that any protection of the brain capillaries at the initial stages of the disease might contribute in the abbreviation of the long chain of pathological alteration, which occur following the disruption of the BBB, which serves as the essential interface between the vascular system and the brain.

Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level.

Role of neuroimaging in multidisciplinary approach towards Non-Alzheimer's dementia.

Dementia is defined as chronic deterioration of intellectual function and cognitive skills significant enough to interfere with the ability to perform daily activities. Recent advances in the treatment of dementia have renewed interest in the use of various neuroimaging techniques that can assist in the diagnosis and differentiation of various subtypes. Neuroimaging and computational techniques have helped the radiological community to monitor disease progression of various neurodegenerative conditions presenting with dementia, such as Alzheimer disease, frontotemporal lobe dementia (FTLD), progressive supranuclear palsy (PSP) and multisystem atrophy-cerebellar variant (MSA-C), and their response to newer therapies. Prompt identification of treatable or reversible forms of dementia, such as tumours, subdural haemorrhage and intracranial dAVF, is crucial for the effective management of these conditions. It is also prudent to recognize the imaging spectrum of metabolic, infective and autoimmune diseases with rapidly progressing dementia, such as methanol toxicity, central pontine myelinolysis (CPM), delayed post hypoxic leukoencephalopathy (DPHL), HIV, Creutzfeldt-Jakob Disease (CJD), Sjogren's syndrome, multiple sclerosis (MS), radiation necrosis and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), which are difficult to treat and often require palliative care. This pictorial review emphasizes various non-Alzheimer’s dementia entities and discusses their imaging highlights.Teaching Points• Non Alzheimer’s dementia constitutes a broad spectrum of conditions.• Neuroimaging plays an important role in differentiating treatable from irreversible dementia.• Neuroimaging is often non-specific in early stages of neurodegenerative conditions with dementia.• Neuroimaging plays an important role in the multimodal approach towards management of dementia.

Case Report: Psychotic Depression with Pseudodementia Misdiagnosed as Dementia Remitted with TCA

Epidemiological research has indicated that elderly patients with depression are at increased risk of subsequent dementia including Alzheimer’s disease. In addition, several studies have also shown that depressive pseudodementia may well develop into irreversible dementia. It is a matter of course, however, that all depressive patients with pseudodementia do not progress to irreversible dementia. The present case is an elderly woman with psychotic depression who was misdiagnosed with dementia because of poor response to serotonin selective reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) as well as a manifestation of moderate cognitive impairment. She was remitted with pharmacotherapy by tricyclic antidepressant (TCA), with no cognitive problems. Psychiatrists should take care not to give too much weight to certain evidence that pseudodementia is a strong predictor of dementia, and should observe individual depressive patients carefully and treat them in any possible way including with TCA or electroconvulsive therapy.

Palliative care and quality of life for people with dementia: medical and psychosocial interventions.

Despite mounting evidence that principles of palliative care are appropriate in care for individuals with dementia they are often not applied. As a result, patients with dementia are often exposed to burdensome interventions that have little or no benefit and are not provided with psychosocial treatments. Recommendations for applying palliative care principles in caring for people with dementia are provided, based on the WHO definition of palliative care, our clinical experience and some key literature reports. People with a diagnosis of an irreversible dementia such as Alzheimer's disease (AD) and their families are rarely informed that this is a terminal disease and palliative care principles are not discussed with them. They are applicable early in the course of illness when the person can still make end-of-life decisions. Palliative care can be used in conjunction with other therapies and services, such as hospice care that provide relief from pain and other distressing symptoms. The care should include keeping people with dementia involved in meaningful activities which decrease or eliminate behavioral symptoms of dementia. Educating families and professionals about palliative care is important as many professionals and non-professionals believe that this approach intends to hasten death, instead of affirming life and regarding dying as a normal process. Living, not just existing, with a dementing illness involves encouraging the person to continue to be involved in meaningful activities. Medical interventions should be compatible with goals of care and balance benefits and burdens for each intervention taking into consideration severity of dementia.

Alzheimer's disease and CADASIL are heritable, adult-onset dementias that both involve damaged small blood vessels.

This essay explores an alternative pathway to Alzheimer's dementia that focuses on damage to small blood vessels rather than late-stage toxic amyloid deposits as the primary pathogenic mechanism that leads to irreversible dementia. While the end-stage pathology of AD is well known, the pathogenic processes that lead to disease are often assumed to be due to toxic amyloid peptides that act on neurons, leading to neuronal dysfunction and eventually neuronal cell death. Speculations as to what initiates the pathogenic cascade have included toxic abeta peptide aggregates, oxidative damage, and inflammation, but none explain why neurons die. Recent high-resolution NMR studies of living patients show that lesions in white matter regions of the brain precede the appearance of amyloid deposits and are correlated with damaged small blood vessels. To appreciate the pathogenic potential of damaged small blood vessels in the brain, it is useful to consider the clinical course and the pathogenesis of CADASIL, a heritable arteriopathy that leads to damaged small blood vessels and irreversible dementia. CADASIL is strikingly similar to early onset AD in that it is caused by germ line mutations in NOTCH 3 that generate toxic protein aggregates similar to those attributed to mutant forms of the amyloid precursor protein and presenilin genes. Since NOTCH 3 mutants clearly damage small blood vessels of white matter regions of the brain that lead to dementia, we speculate that both forms of dementia may have a similar pathogenesis, which is to cause ischemic damage by blocking blood flow or by impeding the removal of toxic protein aggregates by retrograde vascular clearance mechanisms.

Genetic Testing and Alzheimer’s Disease: Implications for Psychiatric-Mental Health Nursing

Alzheimer's disease (AD), the most common cause of irreversible dementia, continues to grow in prevalence as well as public health impact. Extensive research into the genetic etiology of AD has yielded knowledge of some genetic factors that are causative and other genetic factors that increase risk for disease. Consequently, the possibility of genetic testing in individuals with or at risk for AD is a question that nurses may be asked. Psychiatric-mental health (PMH) professionals are in key positions to influence the care of individuals who are considering the effect of genetic information on their health care decisions. Whether by working within interdisciplinary genetic counseling teams to provide direct specialty services or by developing skills to identify and refer individuals at risk for or concerned about their risk for AD, PMH nurses can play an important role in the health care of individuals and families experiencing AD.

Sporadic Alzheimer’s Disease Begins as Episodes of Brain Ischemia and Ischemically Dysregulated Alzheimer’s Disease Genes

The study of sporadic Alzheimer’s disease etiology, now more than ever, needs an infusion of new concepts. Despite ongoing interest in Alzheimer’s disease, the basis of this entity is not yet clear. At present, the best-established and accepted “culprit” in Alzheimer’s disease pathology by most scientists is the amyloid, as the main molecular factor responsible for neurodegeneration in this disease. Abnormal upregulation of amyloid production or a disturbed clearance mechanism may lead to pathological accumulation of amyloid in brain according to the “amyloid hypothesis.” We will critically review these observations and highlight inconsistencies between the predictions of the “amyloid hypothesis” and the published data. There is still controversy over the role of amyloid in the pathological process. A question arises whether amyloid is responsible for the neurodegeneration or if it accumulates because of the neurodegeneration. Recent evidence suggests that the pathophysiology and neuropathology of Alzheimer’s disease comprises more than amyloid accumulation, tau protein pathology and finally brain atrophy with dementia. Nowadays, a handful of researchers share a newly emerged view that the ischemic episodes of brain best describe the pathogenic cascade, which eventually leads to neuronal loss, especially in hippocampus, with amyloid accumulation, tau protein pathology and irreversible dementia of Alzheimer type. The most persuasive evidences come from investigations of ischemically damaged brains of patients and from experimental ischemic brain studies that mimic Alzheimer-type dementia. This review attempts to depict what we know and do not know about the triggering factor of the Alzheimer’s disease, focusing on the possibility that the initial pathological trigger involves ischemic episodes and ischemia-induced gene dysregulation. The resulting brain ischemia dysregulates additionally expression of amyloid precursor protein and amyloid-processing enzyme genes that, in addition, ultimately compromise brain functions, leading over time to the complex alterations that characterize advanced sporadic Alzheimer’s disease. The identification of the genes involved in Alzheimer’s disease induced by ischemia will enable to further define the events leading to sporadic Alzheimer’s disease-related abnormalities. Additionally, knowledge gained from the above investigations should facilitate the elaboration of the effective treatment and/or prevention of Alzheimer’s disease.

MOCA is an integrator of the neuronal death signals that are activated by familial Alzheimer's disease-related mutants of amyloid β precursor protein and presenilins

The death of cholinergic neurons in the cerebral cortex and certain subcortical regions is linked to irreversible dementia relevant to AD (Alzheimer's disease). Although multiple studies have shown that expression of a FAD (familial AD)-linked APP (amyloid β precursor protein) or a PS (presenilin) mutant, but not that of wild-type APP or PS, induced neuronal death by activating intracellular death signals, it remains to be addressed how these signals are interrelated and what the key molecule involved in this process is. In the present study, we show that the PS1-mediated (or possibly the PS2-mediated) signal is essential for the APP-mediated death in a γ-secretase-independent manner and vice versa. MOCA (modifier of cell adhesion), which was originally identified as being a PS- and Rac1-binding protein, is a common downstream constituent of these neuronal death signals. Detailed molecular analysis indicates that MOCA is a key molecule of the AD-relevant neuronal death signals that links the PS-mediated death signal with the APP-mediated death signal at a point between Rac1 [or Cdc42 (cell division cycle 42)] and ASK1 (apoptosis signal-regulating kinase 1).

Prevalence of depressive disorders in the elderly

Community-based mental health studies have revealed that the point prevalence of depressive disorders in the elderly population of the world varies between 10% and 20%, depending on cultural situations. A retrospective study based on analysis of various study reports was conducted, to determine the median prevalence rates of depressive disorders in the elderly population of India and various other countries in the world. All the studies that constituted the sample were conducted between 1955 and 2005. Included are only community-based, cross-sectional surveys and some prospective studies that had not excluded depression at baseline. These studies were conducted on a homogenous community of the elderly population in the world, who were selected by a simple random sampling technique. After applying the inclusion and exclusion criteria on published and indexed articles, 74 original research studies that surveyed a total of 487 275 elderly individuals, in the age group of 60 years and above, residing in various parts of the world, were included for the final analysis. The median prevalence rate and its corresponding interquartile range were calculated. The chi-square test and chi-square for linear trend were applied. A P value of <.05 was considered as statistically significant. The median prevalence rate of depressive disorders in the world for the elderly population was determined to be 10.3% (interquartile range [IQR], 4.7%-16.0%). The median prevalence rate of depression among the elderly Indian population was determined to be 21.9% (IQR, 11.6%–31.1%). Although there was a significant decrease in the trend of world prevalence of geriatric depression, it was significantly higher among Indians, in recent years, than the rest of the world.

Prevalence of treatable and reversible dementias: A study in a dementia outpatient clinic.

Dementia is a syndrome characterized by the development of multiple cognitive deficits and behavioral changes that leads to impairment of functional activities. There are primary degenerative, progressive and irreversible dementias, and other dementias resulting from a progressive but potentially reversible dementia of secondary origin.ObjectiveTo assess the prevalence of cases with a diagnosis of potentially reversible dementia at a Behavioral Neurology Outpatient Unit.MethodsA retrospective study based on a review of 340 medical records of patients seen from 1999 to 2009 was conducted. All patients received a thorough diagnostic assessment to verify the etiological hypothesis proposed.ResultsOf the 340 patients seen in the study period, 172 (50.5%) were females and 168 (49.5%) males, 90 patients (26.4%) were under 60 years of age, and 250 (73.6%) were over 60 years of age. Alzheimer’s disease, with 89 cases (26%), followed by vascular dementia with 39 cases (11.47%), were the leading etiological diagnoses. A total of 193 patients had dementia and 37 of these (19.17%) were found to have potentially reversible dementias, distributed as follows: head injury: 15 patients; alcohol-related dementias: 11 patients; meningoencephalitis: 2 patients; hypothyroidism: 2 patients; neurosyphilis: 2 patients; normal pressure hydrocephalus: 2 patients; AIDS: 1 patient; Korsakoff’s syndrome: 1 patient, and Post-anoxic dementia: 1 patient.ConclusionsA significant number of patients were found to have potentially reversible dementias (19.17%). These data show an urgent need for more extensive diagnostic investigation, and indicate the possibility of reversing some dementias, especially cases detected early.

Alzheimer's dementia begins as a disease of small blood vessels, damaged by oxidative‐induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy

There is a widely shared view among Alzheimer's disease (AD) investigators that the amyloid hypothesis best describes the pathogenic cascade that leads, ultimately, to neuronal degeneration and irreversible dementia. The most persuasive evidence comes from studies of damaged brains of patients in the late stages of AD and from animal studies that attempt to mimic the hereditary forms of early-onset dementia. Despite this impressive body of knowledge, we still lack the means to either arrest or prevent this horrible contagion. This essay attempts to describe what we know, and do not know, about the earliest stages of the disease, focusing on the possibility that the initial pathological changes involve oxidative-induced inflammatory damage to small blood vessels. The resulting ischemia activates amyloid-processing enzymes and other proinflammatory factors that eventually compromise neuronal functions, leading, over time, to the complex lesions that characterize advanced disease. The idea that blood vessel damage is primary has a long history and many prior advocates. The novel addition offered here is the speculation that low-abundance, gain-of-function somatic mutations of the amyloid precursor protein may be part of the triggering mechanism.

Severe dementia: A review about diagnoses, therapeutic management and ethical issues.

North American data show that in the year 2000 around 4.5 million people had a diagnosis of dementia and more than a half were at moderate or severe stages of the disease. There is inevitable cognitive and functional decline caused by all etiologies of irreversible dementia as well as many behavioral symptoms that compromise the quality of life of both patients and caregivers. Few published studies have investigated issues concerning severe dementia such as predictors of mortality and life expectancy, nutrition, end of life issues and palliative care in terminal dementia, as well as best pharmacological and non-pharmacological treatments. Due to the complexity that characterizes advanced dementia, it is important that this discussion starts as early as possible allowing some decisions to be taken, preferably when the patients can still express their opinion.

Distinguishing clinical depression from early Alzheimer's disease in elderly people: Can narrative analysis help?

Background: Differentiating the reversible cognitive symptoms associated with depression (DEP) from the irreversible dementia associated with early or mild Alzheimer's disease (AD) has proven to be challenging, particularly in elderly individuals. Most previous studies have focused on contrasting the cognitive profiles associated with these disorders, often yielding unreliable clinical differences. Although a limited set of studies have identified significant differences between DEP and early AD groups on both basic and high-level language production and comprehension tasks, none has included spoken discourse measures, and several limitations within these language studies indicate that further research is warranted. Aims: This study examined whether depression is associated with a distinct pattern of discourse changes, and thus whether discourse analyses may help discriminate elderly individuals with DEP from those in the early stages of AD. Methods & Procedures: Groups of elderly participants with DEP, mild AD, or no psychiatric or neurological diagnosis, who were matched for age and education level, completed a spoken narrative task and general cognition and high-level language tests. Quantitative, syntactic, and informativeness aspects of the discourse samples were analysed. Outcomes & Results: Significant group differences were observed on the informativeness discourse measures, with AD participants producing less-informative samples than DEP and control participants. DEP and control groups did not significantly differ on any discourse variable. Conclusions: Including discourse sampling and analyses, with a focus on informativeness, into comprehensive assessment protocols may lead to more accurate discrimination of DEP and early AD in the elderly.

Characteristics and diagnostic profile of patients seeking dementia care in a memory clinic in Hong Kong

Seeking medical advice for dementia involves an understanding of norms, values and attitudes towards care-giving and inter-dependency, which are culturally bounded. We hypothesize that local culture and socioeconomic structure affect our Chinese patients who present with forgetfulness to our memory clinic. A retrospective case notes review was undertaken on 454 consecutive patients referred to the memory clinic at Princess Margaret Hospital, Hong Kong. 385 patients were diagnosed with dementia and 27 had mild cognitive impairment. Reversible dementia was identified in 24 patients and normal cognition in 18. In patients with dementia, 55.8% had Alzheimer's disease, 26.2% had vascular dementia, 6.0% had other irreversible dementia, 5.2% had dementia with Lewy bodies, 4.9% had undetermined dementia and 1.8% had frontotemporal dementia. The median duration from symptom onset to medical consultation was two years; 66.5% had advanced disease with initial Mini-mental State Examination scores < or = 17. On their first visit, 85% of patients were living in the community; after two years this proportion had fallen to 63%. Dementia patients in Hong Kong apparently enjoy a long subclinical period and only seek medical attention at late stages. Local Chinese culture and socioeconomic backgrounds could be the main reasons that underlie these observations.

Oral health of people with dementia

Oral health of people with dementia