Roles of specialists in psychogeriatrics

Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP ) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer's disease pathology. To explore the role of mixed Alzheimer's disease and TDP-43 pathologies in clinical Alzheimer's-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer's-type dementia in a large cohort of community-dwelling older subjects. We tested the hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer's-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer's-type dementia. Data came from 946 older adults with ( n = 398) and without dementia ( n = 548) from the Rush Memory and Aging Project and Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present in 496 (52%) subjects, and the pattern of deposition was classified as stage 0 (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43 pathology combined with a pathologic diagnosis of Alzheimer's disease was a common mixed pathology (37% of all participants), and the proportion of subjects with clinical Alzheimer's-type dementia formerly labelled 'pure pathologic diagnosis of Alzheimer's disease' was halved when TDP-43 was considered. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer's disease and TDP-43 pathologies were associated with higher odds of clinical Alzheimer's-type dementia (odds ratio = 6.73, 95% confidence interval = 4.18, 10.85) than pathologic Alzheimer's disease alone (odds ratio = 4.62, 95% confidence interval = 2.84, 7.52). In models examining TDP-43 stage, a dose-response relationship with clinical Alzheimer's-type dementia was observed, and a significant association was observed starting at stage 2, extension beyond the amygdala. In this large sample from almost 1000 community participants, we observed that TDP-43 proteinopathy was very common, frequently mixed with pathological Alzheimer's disease, and associated with a higher likelihood of the clinical expression of clinical Alzheimer's-type dementia but only when extended beyond the amygdala.

THE SOUND OF MUSIC: SHORT-TERM EFFECTS OF LIVE MUSIC PERFORMANCE ON THE COGNITIVE AND EMOTIONAL STATUSES OF RESIDENTIAL PATIENTS WITH MAJOR NEUROCOGNITIVE DISORDER

Network for improving the dementia care system

The American Psychiatric Publishing Textbook of Alzheimer Disease and Other Dementias

Ethical Challenges in Geriatric Psychiatry.

Alzheimer’s disease and other similar dementias are debilitating neurodegenerative disorders whose etiology and pathogenesis remain largely unknown, even after decades of research. With the anticipated increase in prevalence of Alzheimer’s type dementias among the more susceptible aging population, the need for disease-modifying treatments is urgent. While various hypotheses have been put forward over the last few decades, we suggest that Alzheimer’s type dementias are triggered by external environmental factors, co-expressing in individuals with specific genetic susceptibilities. These external stressors are defined in the Iron Dysregulation and Dormant Microbes (IDDM) hypothesis, previously put forward. This hypothesis is consistent with current literature in which serum ferritin levels of individuals diagnosed with Alzheimer’s disease are significantly higher compared those of age- and gender-matched controls. While iron dysregulation contributes to oxidative stress, it also causes microbial reactivation and virulence of the so-called dormant blood (and tissue) microbiome. Dysbiosis (changes in the microbiome) or previous infections can contribute to the dormant blood microbiome (atopobiosis1), and also directly promotes systemic inflammation via the amyloidogenic formation and shedding of potent inflammagens such as lipopolysaccharides. The simultaneous iron dysregulation and microbial aberrations affect the hematological system, promoting fibrin amylodiogenesis, and pathological clotting. Systemic inflammation and oxidative stress can contribute to blood brain barrier permeability and the ensuing neuro-inflammation, characteristic of Alzheimer’s type dementias. While large inter-individual variability exists, especially concerning disease pathogenesis, the IDDM hypothesis acknowledges primary causative factors which can be targeted for early diagnosis and/or for prevention of disease progression.

Evidence-Based Pharmacological Management and Treatment of Behavioral and Psychological Symptoms of Dementia

Background Dementia is a common, disabling disorder of the elderly. With the steady growth in the older population, the rate of dementia is expected to increase two fold by 2030 and three fold by 2050. Dementia of Alzheimer Type (DAT) and vascular dementia (VD) are among the most common types of dementia. Behavioral and psychological symptoms of dementia (BPSD) are associated with increased patient morbidity and carer burden. Aims The objective of this study was to compare symptoms of BPSD in patients with DAT and VD and to explore the correlates of BPSD in patients with DAT and VD. Methods Persons aged over 60 years, attending an outpatient clinic tertiary care centre in Northern India, who met diagnostic criteria for either DAT or VD, were included in the study. Outcomes of interest include socio-demographic details, level of cognitive functioning and the nature and severity of BPSD. Results A total of 64 patients were included in the study, of whom 43 had DAT and 21 suffered from VD. Disturbance of activity levels was the most commonly seen feature of BPSD in both patients with DAT and VAD. There was no significant difference in the levels BPSD or of cognitive functioning between the two groups. Conclusions BPSD is a common feature in patients with dementia. Increased clinician awareness and management of this problem is required to improve patient care and reduce carer burden.

Community-based surveys conducted in Japan investigating the prevalence of dementia and its underlying causes revealed that dementia of Alzheimer's type (DAT) is the most common, followed by vascular dementia (VaD), dementia with Lewy bodies (DLB), mixed dementia, and other conditions including frontotemporal lobar degeneration (FTLD). Accurate differential diagnosis of these disorders requires clarification of their clinical characteristics. The initial symptoms of DAT typically include recent memory loss, episodic memory impairment, and temporal disorientation. Behavioral and psychological symptoms often observed in DAT include delusions of theft, "saving appearance" responses, and head-turning signs. Vascular dementia develops in association with cerebrovascular disease and frequently exhibits a stepwise progression. DLB is characterized by core clinical features such as cognitive fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder. Diagnostic tools such as 123Iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and dopamine transporter (DAT) imaging may aid in diagnosis. In Parkinson's disease with dementia (PDD), cognitive impairment appears more than one year after the onset of parkinsonism. FTLD involves degeneration of the frontal and temporal lobes, leading to prominent changes in personality, behavior, and language function. Several subtypes of FTLD exist depending on the affected brain region, including the behavioral variant of frontotemporal dementia, semantic dementia, and progressive non-fluent aphasia. Idiopathic normal-pressure hydrocephalus (iNPH) is characterized by gait disturbance, urinary incontinence, and dementia, resulting from an abnormal accumulation of cerebrospinal fluid. Pathologically confirmed cases of DLB and progressive supranuclear palsy (PSP) may occasionally present with symptoms resembling iNPH.

Soluble oligomers of amyloid beta (Abeta), rather than amyloid fibrils, have been proposed to initiate synaptic and cognitive dysfunction in Alzheimer's disease (AD). However, there is no direct evidence in humans that this mechanism can cause AD. Here, we report a novel amyloid precursor protein (APP) mutation that may provide evidence to address this question. A Japanese pedigree showing Alzheimer's-type dementia was examined for mutations in APP, PSEN1, and PSEN2. In addition, 5,310 Japanese people, including 2,121 patients with AD, were screened for the novel APP mutation. The pathogenic effects of this mutation on Abeta production, degradation, aggregation, and synaptotoxicity were also investigated. We identified a novel APP mutation (E693Delta) producing variant Abeta lacking gulutamate-22 (E22Delta) in Japanese pedigrees showing Alzheimer's-type dementia and AD. Although the secretion of total Abeta was markedly reduced by this mutation, the variant Abeta was more resistant to proteolytic degradation. The mutant peptides showed the unique aggregation property of enhanced oligomerization but no fibrillization, and inhibited hippocampal long-term potentiation more potently than wild-type peptide in rats in vivo. Consistent with the nonfibrillogenic property of the variant Abeta, a very low amyloid signal was observed in the patient's brain on positron emission tomography using Pittsburgh compound-B. The E693Delta mutation has been suggested as a cause of dementia because of enhanced formation of synaptotoxic Abeta oligomers. Our findings may provide genetic validation in humans for the emerging hypothesis that the synaptic and cognitive impairment in AD is primarily caused by soluble Abeta oligomers.

Background Currently, 5 million seniors who reside in the community or assisted living or nursing facilities are affected by Alzheimer's disease and other neurocognitive disorders. They experience various psychiatric symptoms. Also, their family members are stressed from caregiving, and may feel guilty for not doing more. Methods We created an innovative nonpharmacological intervention, AlzhaTV to decrease behavioral and psychological symptoms associated with neurocognitive disorders. We offered AlzhaTV to 9 nursing home patients. Results In our retrospective examination of this case series, we found AlzhaTV was effective in reducing behavioral and psychological symptoms in patients with neurocognitive disorders. We achieved either dose reductions, discontinuation, or avoided initiating the use of antipsychotic medications and benzodiazepines in nearly all patients. Conclusions AlzhaTV may help decrease behavioral and psychological symptoms of dementia and decrease or avoid the use of antipsychotic medications or benzodiazepines. It may help in reducing the overall cost of health care in patients with dementia or neurocognitive disorders. AlzhaTV helps patients stay connected to their families, friends, and their past while bringing them joy in the present. It also helps families and caregivers feel more connected and less helpless.

A systematic review and meta‐analysis encompassing 66 studies has found limited evidence of benefits from medication treatments for clinical Alzheimer's‐type dementia. There was some evidence supporting cholinesterase inhibitors over placebo for cognitive and functional outcomes, but little evidence supporting any treatment for behavioral and psychological symptoms of dementia.

Although much is known about the relationship between neuropsychiatric problems and the severity of cognitive impairments, relatively little is known about the association with specific cognitive impairments. The aim of this study was to determine whether specific cognitive impairments are predictive of neuropsychiatric problems. One hundred twenty-six patients were evaluated every 6 months for 2 years. In particular, a low level of language expression was related to higher levels of overall neuropsychiatric problems and to psychosis. Impairment of abstract reasoning was related to psychosis and aberrant motor behavior.

Essential oil from Rosmarinus officinalis (Rosemary essential oil, EORO) may improve cognitive function by activating the central nervous system. However, no scientific basis for the effect of EORO has been described. Therefore, we investigated the effect of EORO on Alzheimer's type dementia using model mice. Mice were administered EORO by inhalation. Then, scopolamine was used to prepare Alzheimer's type dementia model mice. To evaluate cognitive function, the Y‐maze test was used for assessment of short‐term memory. EORO produced a significant improvement in the rate of spontaneous alternation behavior. Furthermore, 1,8‐cineole, α‐pinene, and β‐pinene, the main components of EORO, were detected in the brain in a concentration‐dependent manner following inhalation of EORO. Thus, inhalation of EORO may improve cognitive function in a model of Alzheimer's type dementia. Components such as 1,8‐cineole and others are likely involved in the effects on the brain. Examination of the detailed mechanism of action of EORO is necessary for future clinical application.

Two psychometric tests designed to evaluate "verbal fluency" and "naming" as a measure of semantic memory were presented to 18 patients with Alzheimer's-type dementia, 16 other patients with multi-infarct dementia, and 14 age-matched control subjects. The diagnosis of multi-infarct dementia and Alzheimer's-type dementia was based on the commonly accepted criteria of the Diagnostic and Statistical Manual of Mental Disorders, ed 3. Although the patients with Alzheimer and multi-infarct dementias, respectively, suffered from a comparable degree of dementia (as determined by the Mini-Mental State examination), semantic memory was not specifically impaired in Alzheimer's-type dementia as opposed to multi-infarct dementia. In contrast semantic memory was correlated with the degree of dementia in both disease entities.