Insight for impairment in independent living skills in Alzheimer's disease and multi-infarct dementia

Abstract

Dementing diseases cause a deterioration in the capacity for independent living skills (ILS). The present study investigated the level of insight in ILS impairment in 12 Alzheimer's diseace (AD) patients, 12 multi-infarct dementia (MID) patients, and 12 normal elderly controls, using two different measurement techniques: informant report and patient self-report. Pairwise comparisons at the .05 level revealed a significantly greater loss of insight for ILS impairment in AD patients as compared to both controls and MID patients. Additional analyses revealed that loss of insight, operationally defined as the discrepancy between informant report and patient self-report, was not significantly related to age, education, mental status, or level of depression, but was significantly related to degree of caregiver burden. These results indicate that intervention strategies are needed that take into consideration the level of patient insight for ILS impairment, as well as the caregiver's perception of the patient's capabilities and the degree of burden experienced by the caregiver.     

Ventromedial‐frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer's disease

Loss in insight is a major feature of frontotemporal dementia (FTD) but has been investigated relatively little. More importantly, the neural basis of insight loss is still poorly understood. The current study investigated insight deficit profiles across a large cohort of neurodegenerative patients (n = 81), including FTD and Alzheimer's disease (AD) patients. We employed a novel insight questionnaire, which tapped into changes across different domains: social interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes varied considerably for insight loss, with the behavioral variant worst and the progressive non‐fluent variant least affected. All other subtypes and AD showed milder but consistent insight loss. Voxel‐based morphometry analysis revealed that overall insight loss correlated with ventromedial and frontopolar prefrontal atrophy, with exception of social interaction and emotion insight loss, which additionally correlated with lateral temporal and amygdala atrophy, respectively. Our results show that patients with neurodegenerative conditions show variable loss of insight, with ventromedial and frontopolar cortex regions appearing to be particularly important for insight. Hum Brain Mapp 35:616–626, 2014. © 2012 Wiley Periodicals, Inc.     

Getting Real

We cannot know how our physical selves affect our patients and the course of an analysis. I tackle this topic through a case study of one patient's responses to my weight loss. For a patient's perspective, I use Margaret Little's accounts of her analyses with Ella Freeman Sharpe and D.W. Winnicott. She describes her struggle to verbalize the reality she sees in their appearance. Little, along with additional readings from Ferenczi and Levenson, helps me consider my relationship with my patient and identify a need for bolder inquiry about my changing body. I embark on an experiment with this patient, and the outcome surprises me. The treatment opens up and my inquiry yields an enactment with fresh historical data and new insight.     

Failure to detect an association between self-reported traumatic brain injury and Alzheimer's disease neuropathology and dementia

IntroductionRecent research with neuropathologic or biomarker evidence of Alzheimer's disease (AD) casts doubt on traumatic brain injury (TBI) as a risk factor for AD. We leveraged the National Alzheimer's Coordinating Center to examine the association between self-reported TBI with loss of consciousness and AD neuropathologic changes, and with baseline and longitudinal clinical status.MethodsThe sample included 4761 autopsy participants (453 with remote TBI with loss of consciousness; 2822 with AD neuropathologic changes) from National Alzheimer's Coordinating Center.ResultsSelf-reported TBI did not predict AD neuropathologic changes (P > .10). Reported TBI was not associated with baseline or change in dementia severity or cognitive function in participants with or without autopsy-confirmed AD.DiscussionSelf-reported TBI with loss of consciousness may not be an independent risk factor for clinical or pathological AD. Research that evaluates number and severity of TBIs is needed to clarify the neuropathological links between TBI and dementia documented in other large clinical databases.     

Le concept d’insight narratif chez les personnes souffrant de schizophrénie : une revue systématique de la littérature

AimThe aim of this systematic revue of literature is to examine articles dealing with the narrative insight (patient's explanatory models of his difficulties) in patients suffering from schizophrenia. In addition to the theoretical interest of this work, it would make it possible to better adjust the clinical practices concerning the stories of patients about their disorders.MethodA study was conducted using the databases ScienceDirect, Medline, PsychInfo and PubPsych using the key words “narrative insight”, “cultural insight”, “subjective insight”, “narrative awareness”, “mental illness”, and “psychiatric disorder”. This search by keywords led to eighty-six results; abstracts of all the articles were consulted. Then the authors selected and studied all articles corresponding to inclusion criteria and compared their results and reached agreement by consensus in case of difference. The theme of the study was to focus on the concept of narrative insight or any other close concept mentioning an explanatory model of mental and/or psychiatric disorders, moving away from the biomedical model. Nine articles were selected based on the inclusion criteria (articles published in peer reviewed journals, where the both the resume and article are accessible; articles dealing with narrative insight of people suffering from schizophrenia).ResultsThe authors of these articles agree that awareness of mental illness, insight, is a narrative act in which people give a personal meaning to their disorder. The most popular biomedical model used has many limitations and is the subject of many controversies. Results of the conducted study suggest considering narrative insight as adaptive strategies to mental illnesses. Indeed the process of narrative insight essentially consists in the patient adapting his life story to his conceptions and his values. To tell the story of one's own troubles with one's own values and beliefs gives meaning that helps protect identity and give back hope. This concept is considered to be dynamic and multidimensional. In addition, studies highlight its positive effects including the simultaneous presence of several models, which would have a greater favorable impact on the prognosis than the medical explanation alone.ConclusionIt seems necessary to take into account the concept of narrative insight in order to evaluate insight of patients suffering from mental illness. This implies that the evaluation methods of insight as well as the clinical practice must evolve to adapt to the culture and subculture of the patient. This could have beneficial effects on the well-being of patients, therapeutic relations, access to treatment as well as psychiatric research, as well as limit controversies around this topic. It would be interesting to confirm this new conception of insight and the therapeutic relations by carrying out new studies as well as by starting to take it into account in patient care.     

Cognitive,neuroimaging, and pathological studies in a patient with Pick's disease

We conducted cognitive, imaging, and neuropathological studies on a patient with Pick's disease. The patient was impaired at interpreting sentences with complex grammatical constructions, differing significantly from control subjects and patients with Alzheimer's disease (AD). Evaluation of regional brain functioning at rest, with positron emission tomography, revealed reduced left frontal activity compared with control subjects and AD patients. Autopsy demonstrated the classic pathology of Pick's disease, including massive neuron loss and gliosis in the frontal and cingulate cortex as well as numerous tau-positive hippocampal Pick bodies. The abnormal tau proteins were phosphorylated at the same amino acid residues as AD paired helical filament tau (PHFtau), but they exhibited a unique migration profile on western blot. Our observations support the hypothesis that a distinct variety of hyperphosphorylated tau in Pick's disease compromises the long-term viability of selectively vulnerable populations of neurons in frontal cortices that contribute to sentence processing.     

Cognitive rehabilitation two and one-half years post right temporal lobectomy

Abstract

A 45-year old radiologist, who underwent a right temporal lobectomy to remove a tumor, sought treatment for difficulties with attention/scanning, sustained concentration, leisure reading, driving, and self-monitoring in social situations. A neuropsychological evaluation conducted 2.5 years postsurgery revealed impaired visual-spatial memory, inefficiency in general visual scanning, a mild left-sided neglect, and diminished social perception. The patient subsequently underwent a 4-month cognitive retraining program, which was tailored to his specific neuropsychological deficits. At the termination of treatment, improvements were observed on follow-up neuropsychological data, behavioral observations made by the patient's wife, and efficiency on work-related tasks. This case illustrates the ecological validity of cognitive rehabilitation procedures and emphasizes the need to tailor the procedures to specific cognitive deficits revealed on neuropsychological testing.     

Donepezil increases regional cerebral blood flow in a case of Korsakoff syndrome

Cholinesterase inhibitors improve cognitive functions and regional cerebral blood flow (rCBF) in mild to moderate Alzheimer's disease (AD). Recently, the possibility has been suggested that in patients with dementia other than AD cholinesterase inhibitors are useful for the treatment of their cognitive impairment and behavioral symptoms. In the present study we report the effectiveness of donepezil for a patient with Korsakoff syndrome. The patient was a 65‐year‐old man who gradually showed disturbances in memory, attention and concentration. The etiology was considered to be alcoholism. He would indulge in drinking and repeatedly asked the same questions over and over. He also developed emotional fluttering and would not settle down. On admission, he showed a severe memory deficit, disorientation and momentary confabulation. It was obvious that the patient was inactive and not spontaneous. He also manifested disinhibited behaviors. The patient's confabulation gradually diminished in hospital. He had no focal neurological deficit. Cranial magnetic resonance imaging (MRI) did not reveal any abnormality. Single photon emission computed tomography (SPECT) with 99 m‐TC‐ hexamethyl propylamenamine oxide (HMPAO) indicated hypoperfusion in the left thalamus, left basal ganglia and bilateral medial temporal lobes. In order to improve his cognitive function, the patient was treated donepezil. An evaluation of the effects of donepezil on rCBF was performed with the images showing a remarkable improvement in cerebral perfusion in the right medial temporal, the left thalamus and basal ganglia. However, the patient's memory impairment, disorientation, disinhibition, and stereotypical behavior and utterance were not improved. As an explanation, it was speculated that his neural network might be damaged so severely that there was no room for improvement by the acetylcholinesterase inhibitors.     

Rating scales for behavioral symptoms in Huntington's disease: Critique and recommendations

Behavioral symptoms are an important feature of Huntington's disease and contribute to impairment in quality of life. The Movement Disorder Society commissioned the assessment of the clinimetric properties of rating scales in Huntington's disease to make recommendations regarding their use, following previously used standardized criteria. A systematic literature search was conducted to identify the scales used to assess behavioral symptoms in Huntington's disease. For the purpose of this review, 7 behavioral domains were deemed significant in Huntington's disease: irritability, anxiety, depression, apathy, obsessive‐compulsive behaviors, psychosis, and suicidal ideation. We included a total of 27 behavioral rating scales, 19 of which were of a single behavioral domain and the remaining 8 scales included multiple behavioral domains. Three rating scales were classified as “recommended” exclusively for screening purposes: the Irritability Scale for irritability, the Beck Depression Inventory‐II, and the Hospital Anxiety and Depression Scale for depression. There were no “recommended” scales for other purposes such as diagnosis, severity, or change in time or to treatment. The main challenges identified for assessment of behavioral symptoms in Huntington's disease are the co‐occurrence of multiple behavioral symptoms, the particular features of a behavioral symptom in Huntington's disease, and the need to address stage‐ and disease‐specific features, including cognitive impairment and lack of insight. The committee concluded that there is a need to further validate currently available behavioral rating scales in Huntington's disease to address gaps in scale validation for specific behavioral domains and purpose of use. © 2016 International Parkinson and Movement Disorder Society     

Insight for impairment in independent living skills in Alzheimer's disease and multi-infarct dementia

Dementing diseases cause a deterioration in the capacity for independent living skills (ILS). The present study investigated the level of insight in ILS impairment in 12 Alzheimer's disease (AD) patients, 12 multi-infarct dementia (MID) patients, and 12 normal elderly controls, using two different measurement techniques: informant report and patient self-report. Pairwise comparisons at the .05 level revealed a significantly greater loss of insight for ILS impairment in AD patients as compared to both controls and MID patients. Additional analyses revealed that loss of insight, operationally defined as the discrepancy between informant report and patient self-report, was not significantly related to age, education, mental status, or level of depression, but was significantly related to degree of caregiver burden. These results indicate that intervention strategies are needed that take into consideration the level of patient insight for ILS impairment, as well as the caregiver's perception of the patient's capabilities and the degree of burden experienced by the caregiver.     

Depression and Increased Risk of Alzheimer's Dementia: Longitudinal Analyses of Modifiable Risk and Sex-Related Factors

ObjectiveOur understanding of why older adults with depression are at increased risk of Alzheimer's disease (AD) remains incomplete. Most adults living with AD are women, and women have a near twofold lifetime risk of depression. We examined the risk of depression upon incident AD, and how sex influences this risk.MethodsUsing the National Alzheimer's Coordinating Center database, older adults (age 50+) with normal cognition, who visited memory clinics across the United States between September 2005 and December 2019, were followed until first diagnosis of AD or loss to follow up. Multivariable survival analyses were performed to determine if recent and/or remote depression were independent risk factors for AD, if this depression-related risk exists for each sex or was moderated by sex.ResultsSix hundred and fifty-two of 10,739 enrolled participants developed AD over a median follow-up of 55.3 months. Recent depression (active within the last 2 years) was independently associated with increased risk of AD (hazard ratio [HR] = 2.0; 95%CI, 1.5–2.6) while a remote history of depression was not (HR = 1.0; 95%CI, 0.7–1.5). After stratification by sex, recent depression was an independent predictor in females (HR = 2.3; 95%CI, 1.7–3.1) but not in males (HR = 1.4; 95%CI, 0.8–2.6). No interaction between recent depression and sex was observed.ConclusionOnly a recent history of depression was associated with higher risk of AD. This association was significant among women only, but was not moderated by sex. Future analyses should determine if these findings extend to other populations and may be explained by variable distribution of neurobiological or other modifiable risk factors between the sexes.     

强迫症共病疾病焦虑障碍的临床访谈

为了提高广大精神心理科医务工作者的临床访谈及诊断技能,本文对一例较特殊的合并了两种强迫谱系障碍的患者进行了案例访谈报告。这是一位27岁的男性患者,执着于练习弹钢琴十几年,仪式化的行为与执着让患者不能正常工作,成为大家眼中的怪人。离职后逐渐开始关注排便问题,纠结于便秘、腹胀等感受问题,总认为自己患有肛肠疾病,开始反复检查就诊。在检查无明显异常的情况下,反复要求行手术治疗四次以解决肛肠问题,结果越治越难受。本案例患者被诊断为强迫症共病疾病焦虑障碍,需要采取生物-心理-社会的综合治疗。调整以往用药,加强运动,调整饮食结构。施行强迫症一线治疗方案,焦虑缓解后进行认知行为疗法(CBT)来改善自我认知,减轻心理压力。今后工作中放弃不切实际的想法,学习应对策略,合理安排工作和生活。     

Is the pathology of corticobasal syndrome predictable in life?

Corticobasal syndrome (CBS) has been associated with a heterogeneous spectrum of pathologies with an increasing number of reports of Alzheimer's type pathology. There is, however, no means of predicting pathology of CBS in vivo at present. We compared the clinical features of patients presenting with CBS who have either pathologic changes of classic corticobasal degeneration (CBD) or Alzheimer's disease (AD) at post‐mortem to identify predictors of the specific pathological processes in life. Twelve patients with CBS were followed prospectively; six had AD and six had classic CBD neuropathology. After review of the presenting clinical features, we identified nine potential predictor variables, compared their frequency in the two groups, and performed a discriminant function analysis. Initial episodic memory complaints and poor performance on the combined orientation‐memory subtest of the Addenbrooke's Cognitive Examination (ACE) reliably predicted AD pathology while varying combinations of early frontal‐lobe type behavioral symptoms, nonfluent language disturbance, orobuccal apraxia, and utilization behavior predicted CBD pathology ante‐mortem. CBS is frequently associated with Alzheimer's disease pathology. Early episodic memory impairment versus early behavioral symptomatology appears to best predict AD or CBD pathology in life. © 2009 Movement Disorder Society     

Longitudinal study of self-imposed driving restrictions and deficit awareness in patients with Alzheimer disease.

Thirty-five patients with Alzheimer disease (AD), including 19 who were still driving, were evaluated for level of awareness and driving status. There was no significant correlation between driving status and Mini-Mental State Examination (MMSE) scores. Only the attention subscore of the awareness questionnaire yielded a statistically significant difference between drivers and nondrivers. Follow-up of the patients who were still driving was conducted 12-18 months later. All but 4 patients had stopped driving. Caregivers responded to a questionnaire assessing the patient's driving behaviors since the onset of AD. There was no correlation between MMSE and driving status. In 7 of 10 cases, caregivers or patients made the decision that the patient should stop driving. However, caregivers reported long periods between the caregiver's perception that the patient should stop driving and actual cessation (0.5-48 months). Results suggest that AD patients do restrict several areas of their driving voluntarily and that a failure to do so may be associated with an awareness deficit. In particular, a deficit of awareness for attention was significantly associated with an absence of restricted driving behaviors such as avoiding unfamiliar routes. Awareness of a deficit that is related to driving performance may be critical to restricted driving behavior, and this change in behavior may enable the patient to prolong his or her status as a driver.     

Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder characterized by excessive deposition of β‐amyloid (Aβ) oligomers, and neurofibrillary tangles (NFTs), comprising of hyperphosphorylated tau proteins. The cholinergic system has been suggested as the earliest and most affected molecular mechanism that describes AD pathophysiology. Moreover, cholinesterase inhibitors (ChEIs) are the potential class of drugs that can amplify cholinergic activity to improve cognition and global performance and reduce psychiatric and behavioral disturbances. Approximately, 60%‐80% of all cases of dementia in the world are patients with AD. In view of the continuous rise of this disease especially in the aged population, there is a dire need to come up with a novel compound and/or mixture that could work against this devastating disease. In this regard, the best is to rely on natural compounds rather than synthetic ones, because natural compounds are easily available, cost‐effective, and comparatively less toxic. To serve this purpose, lately, scientific community has started exploring the possibility of using different polyphenols either solitary or in combination that can serve as therapeutics against AD. In the current article, we have summarized the role of various polyphenols, namely quercetin, resveratrol, curcumin, gallocatechins, cinnamic acid, caffeine, and caffeic acid as an inhibitor of cholinesterase for the treatment of AD. We have also tried to uncover the mechanistic insight on the action of these polyphenols against AD pathogenicity.     

Apolipoprotein E genotype in diverse neurodegenerative disorders

While the apolipoprotein E (ApoE) ?4 allele is a recognized risk factor for Alzheimer's disease (AD), an association of ?4 with other neurodegenerative diseases (NDs) has not been extensively explored. We examined 51 cases of neuropathologically confirmed ND. After eliminating 18 cases exhibiting pathology sufficient to warrant an additional diagnosis of AD, three disorders characterized by τ-related cytoskeletal pathology, i.e., Pick's disease, corticobasal degeneration, and progressive supranuclear palsy, showed increased ?4 frequencies. Since the number of cases within each category was small, these increased ?4 frequencies were not statistically significant. β-Amyloid (βA4) immunoreactive diffuse plaques were observed in many of these cases. While we cannot eliminate the possibility that these patients were destined to develop AD, these changes may merely reflect an independent association of ?4 with amyloid deposition. These preliminary data affirm the need for further study of well-characterized cases to explore the relationship of ApoE to cytoskeletal pathology and ND.     

A case study of an emerging visual artist with frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Patients presenting with left-sided FTLD syndromes sometimes develop a new preoccupation with art, greater attention to visual stimuli, and increased visual creativity. We describe the case of a 53-year-old, right-handed man with a history of bipolar disorder who presented with language and behavior impairments characteristic of FTLD, then developed motor symptoms consistent with a second diagnosis of amyotrophic lateral sclerosis. Though the patient had never created visual art before, he developed a compulsion for painting beginning at the earliest stages of his disease, and continued producing art daily until he could no longer lift a paintbrush because of his motor deficits. Upon autopsy, he was found to have ubiquitin and TDP43-positive inclusions with MND pathology. This case study details the patient's longitudinal neuropsychological, emotional, behavioral, and motor symptoms, along with structural imaging, neurologic, and neuropathologic findings. Multiple examples of the patient's art are depicted throughout all stages of his illness, and the possible cognitive, behavioral, and neurologic correlates of his new-onset visual artistry are discussed.     

Pattern separation and pattern completion in Alzheimer's disease: Evidence of rapid forgetting in amnestic mild cognitive impairment

Over the past four decades, the characterization of memory loss associated with Alzheimer's disease (AD) has been extensively debated. Recent iterations have focused on disordered encoding versus rapid forgetting. To address this issue, we used a behavioral pattern separation task to assess the ability of the hippocampus to create and maintain distinct and orthogonalized visual memory representations in patients with amnestic mild cognitive impairment (aMCI) and mild AD. We specifically used a lag‐based continuous recognition paradigm to determine whether patients with aMCI and mild AD fail to encode visual memory representations or whether these patients properly encode representations that are rapidly forgotten. Consistent with the rapid forgetting hypothesis of AD, we found that patients with aMCI demonstrated decreasing pattern separation rates as the lag of interfering objects increased. In contrast, patients with AD demonstrated consistently poor pattern separation rates across three increasingly longer lags. We propose a continuum that reflects underlying hippocampal neuropathology whereby patients with aMCI are able to properly encode information into memory but rapidly lose these memory representations, and patients with AD, who have extensive hippocampal and parahippocampal damage, cannot properly encode information in distinct, orthogonal representations. Our results also revealed that whereas patients with aMCI demonstrated similar behavioral pattern completion rates to healthy older adults, patients with AD showed lower pattern completion rates when we corrected for response bias. Finally, these behavioral pattern separation and pattern completion results are discussed in terms of the dual process model of recognition memory. © 2013 Wiley Periodicals, Inc.     

THE BEHAVIOR PATHOLOGY IN ALZHEIMER'S DISEASE RATING SCALE (BEHAVE-AD): RELIABILITY AND ANALYSIS OF SYMPTOM CATEGORY SCORES

The interrater reliability of the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), a psychiatric rating scale especially designed for the evaluation of behavioral disturbances in dementia patients, was studied in both English-speaking US patients and a French-speaking elderly patient population from France. Additionally, the quantitative relationship between severity of Alzheimer's disease (AD) and mean scores on each of the BEHAVE-AD categories and mean total BEHAVE-AD score was determined in a separate study of 140 patients diagnosed as having probable AD. In both reliability studies significant correlations were obtained for all BEHAVE-AD symptom category scores and for mean total BEHAVE-AD scores. Analysis of BEHAVE-AD scores as a function of disease severity demonstrated a non-linear relationship between severity of behavioral symptoms and the global and cognitive advance of AD. Moreover, score analysis of the BEHAVE-AD indicates that these behavioral disturbances become most severe in the moderate and moderately severe stages of the illness. The results of these studies provide support for the reliability of the BEHAVE-AD. Additionally, the BEHAVE-AD provides basic knowledge about the nature and severity of the behavioral symptoms in AD. The latter information may be useful for the development of appropriate and effective psychopharmacologic intervention strategies for these difficult to manage behaviors. Furthermore, these results have implications for the methodology of pharmacologic trials of putative cognitive-enhancer compounds in AD.     

Radio Signal Sensing and Signal Processing to Monitor Behavioral Symptoms in Dementia: A Case Study

ObjectivesAlzheimer's Disease (AD)-related behavioral symptoms (i.e. agitation and/or pacing) develop in nearly 90% of AD patients. In this N = 1 study, we provide proof-of-concept of detecting changes in movement patterns that may reflect underlying behavioral symptoms using a highly novel radio sensor and identifying environmental triggers.MethodsThe Emerald device is a Wi-Fi-like box without on-body sensors, which emits and processes radio-waves to infer patient movement, spatial location and activity. It was installed for 70 days in the room of patient ‘E’, exhibiting agitated behaviors.ResultsDaily motion episode aggregation revealed motor activity fluctuation throughout the data collection period which was associated with potential socio-environmental triggers. We did not detect any adverse events attributable to the use of the device.ConclusionThis N-of-1 study suggests the Emerald device is feasible to use and can potentially yield actionable data regarding behavioral symptom management. No active or potential device risks were encountered.