A prospective study of dementia with Lewy bodies

BACKGROUND: little is known about the longitudinal course of dementia with Lewy bodies (DLB) and how this differs from Alzheimer's disease (AD). METHOD: standardized baseline and annual assessments of cognitive and non-cognitive symptoms are reported in a cohort of 72 patients with DLB or AD. AD was diagnosed using the NINCDS ADRDA criteria and DLB was diagnosed with the criteria of McKeith et al. Cognitive assessment was undertaken using the MMSE schedule and operationalized definitions were used to diagnose non-cognitive symptoms. RESULTS: 42 patients with DLB and 30 patients with AD were assessed. Of the 19 on whom post mortem examinations have been performed, 18 (95%) have had the clinical diagnosis confirmed. DLB patients were significantly more likely to experience visual hallucinations, disturbances of consciousness and parkinsonism at both baseline and at annual assessments. Of DLB patients exposed to neuroleptics, 33% developed sensitivity reactions. The magnitude and pattern of cognitive decline was similar in both groups. CONCLUSION: the importance of the core features highlighted in the newly proposed consensus DLB criteria is supported. These features appear to be stable over time.     

Usefulness of [123I]metaiodobenzylguanidine ([123I]MIBG) myocardial scintigraphy in differentiating between Alzheimer's disease and dementia with Lewy bodies

OBJECTIVE: To confirm the clinical usefulness of [123I] metaiodobenzylguanidine ([123I]MIBG) myocardial scintigraphy in the antemortem differential diagnosis between patients with Alzheimer's disease (AD) and those with dementia with Lewy bodies (DLB). PATIENTS AND METHODS: We compared cardiac [123I] MIBG uptake in 10 patients with AD with that in 10 patients with DLB. We selected the patients with AD or DLB by using stringent diagnostic criteria that combined commonly used clinical criteria with tau protein levels in cerebrospinal fluid and radiographical examinations. RESULTS: The heart to mediastinum ratio of [123I]MIBG uptake in all the patients with DLB was significantly lower than that in the patients with AD (p<0.01). CONCLUSION: This study confirms that [123I]MIBG myocardial scintigraphy is useful in the antemortem differential diagnosis of AD and DLB.     

Differentiating Dementia with Lewy Bodies from Alzheimer's Disease Using the Fall Risk Evaluation Questionnaire

Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer''s disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis. Methods We enrolled patients diagnosed with DLB (n=410) and AD (n=2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants. Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895). Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.     

Prodromal dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementing disorder after Alzheimer's disease (AD), but there is limited information regarding the prodromal DLB state compared with that of AD. Parkinson's disease (PD) and DLB share common prodromal symptoms with Lewy body disease (LBD), allowing us to use a common strategy for identifying the individuals with an underlying pathophysiology of LBD. Dysautonomia, olfactory dysfunction, rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms antedate the onset of dementia by years or even decades in patients with DLB. Although RBD is the most potentially accurate prodromal predictor of DLB, disease progression before the onset of dementia could differ between the prodromal DLB state with and without RBD. Experts who specialize in idiopathic RBD and DLB might need communication in order to clarify the clinical relevance of RBD with the disease progression of DLB. The presence of prodromal LBD symptoms or findings of occipital hypoperfusion/hypometabolism helps us to predict the possible pathophysiological process of LBD in non‐demented patients. This approach might provide the opportunity for additional neuroimaging, including cardiac ¹²³I‐metaiodobenzylguanidine scintigraphy and dopamine transporter imaging. Although limited radiological findings in patients with prodromal DLB states have been reported, there is now a need for larger clinical multisite studies with pathological verification. The long prodromal phase of DLB provides a critical opportunity for potential intervention with disease‐modifying therapy, but only if we are able to clearly identify the diversity in the clinical courses of DLB. In the present article, we reviewed the limited literature regarding the clinical profiles of prodromal DLB. Geriatr Gerontol Int 2015; 15: 817–826.     

Awareness of memory deficits in patients with dementias: a study with the Everyday Memory Checklist

AIM: We examined the level of awareness of memory deficits in 63 patients with Alzheimer's disease (AD), 17 patients with dementia with Lewy bodies (DLB), 14 patients with vascular dementia (VaD), and 56 patients with amnestic mild cognitive impairment (MCI). METHODS: The unawareness of memory impairment was evaluated with a standardized memory questionnaire system based on the Everyday Memory Checklist (EMC). The EMC scores for the patient's own rating, the caregivers' rating and the unawareness score, defined as the discrepancy between these (caregiver rating-patient rating), were analyzed. RESULTS: Although the EMC self-rating scores were comparable among the four groups, the EMC scores in caregivers were significantly higher in the AD group than in the DLB, VaD, and MCI groups. Therefore, the unawareness scores were significantly higher in the AD groups than in other groups. When an unawareness score of 9 or more was defined as significant, impaired awareness was found in 41 (65%) patients with AD, 1 (6%) patient with DLB, 5 (36%) patients with VaD, and in 19 (34%) patients with MCI. CONCLUSION: We found that impaired awareness was found in two-thirds of patients with mild AD and even in one-third of patients with MCI. However, other dementias, in particular DLB, had less severe and less frequent unawareness of memory deficits than AD, suggesting the difference in the pathophysiology between them.     

Prevalence and severity of gait disorders in Alzheimer's and non-Alzheimer's dementias

OBJECTIVES: To compare the prevalence, severity, and type of gait and balance disorders in Alzheimer's disease (AD), vascular dementia (VaD), Parkinson's disease with dementia (PDD), dementia with Lewy bodies (DLB), Parkinson's disease without dementia (PD), and age-matched controls. DESIGN: Cross-sectional. SETTING: Secondary care clinics in geriatric psychiatry, neurology, and geriatrics. PARTICIPANTS: Two hundred forty-five participants aged 65 and older (AD, n=40; VaD, n=39; PDD, n=46; DLB, n=32; PD, n=46; and controls, n=42). MEASUREMENTS: Prevalence and severity of gait and balance disorders were assessed using the Tinetti gait and balance scale. The types of gait disorders in each diagnostic group were classified using the Nutt et al. classification. RESULTS: Gait and balance disorders were more common with PDD (93%), VaD (79%), and DLB (75%) than with PD (43%) and AD (25%) and in controls (7%). The risk of gait and balance disorder was higher in the non-Alzheimer's dementia groups (VaD, PDD, and DLB) than in the AD group (odds ratio=15 (95% confidence interval=6-37). If a gait disorder was present in mild dementia (Cambridge Examination for Mental Disorders of the Elderly cognitive subsection score >65), this was diagnostic of non-Alzheimer's dementia, with sensitivity of 78% and specificity of 100%. Non-Alzheimer's dementia groups had worse Tinetti gait and balance scores than the AD group (all P<.001). The types of gait disorders discriminated between non-Alzheimer's dementias. CONCLUSION: The findings support the idea that gait and balance assessment may augment the diagnostic evaluation of dementia.     

Distinguishing dementia with Lewy bodies from dementia occurring in Parkinson's disease: A literature review

There has been considerable debate as to whether dementia with Lewy bodies (DLB) represents a distinct diagnosis or lies on a spectrum with Parkinson's disease dementia (PDD). The objective of this review was to identify whether conceptualising these dementias as distinct diagnostic entities is meaningful, or indeed possible. A literature review was conducted using the databases MEDLINE and PSYCHINFO. DLB and PDD share many clinical features including the pattern of cognitive deficits and Lewy‐body pathology. However, they may be usefully distinguished by their clinical course and differential response to treatment. Some patients with DLB have a rapidly progressive dementia and may be particularly sensitive to neuroleptic medication, resulting in considerable morbidity and mortality.     

Neuropsychiatric assessment of Alzheimer's disease and related dementias.

Alzheimer's disease (AD) patients exhibit a variety of behavioral alterations including agitation, apathy, depression, anxiety, delusions, irritability and disinhibition. Most patients with AD exhibit neuropsychiatric symptoms, and behavioral changes become more frequent with advancing disease severity. The NPI is a valid and reliable means of assessing neuropsychiatric symptoms in patients with dementia. The NPI correlates with increasing disability in activities of daily living and increasing cognitive impairment. Physical illness contributes little to behavioral symptoms measured by the NPI. Reduced frontal lobe metabolism and perfusion have been identified in patients with apathy, agitation, psychosis and depression. Patients with elevated agitation scores on the NPI have a higher burden of frontal lobe neurofibrillary tangles than patients without agitation. The NPI is sensitive to behavioral improvements following treatment with cholinesterase inhibitors and psychotropic agents. Neuropsychiatric symptom profiles differ among dementia syndromes, and the NPI provides a means of assessing neuropsychiatric symptoms that may aid in differential diagnosis. Evaluation of neuropsychiatric symptoms is a critical aspect of dementia diagnosis and management.     

Dementia with Lewy bodies

The presence of a high number of Lewy bodies--the morphological marker of Parkinson's disease--in the cerebral cortex of some cases of dementia has been frequently observed in association to Alzheimer type lesions (mainly senile plaques) and changes in the substantia nigra, that may be held responsible for the frequently associated symptoms of parkinsonism. The term "dementia with Lewy body" (DLB) has recently been suggested by a consensus conference and indicates that the pathogenetic mechanism of the dementia remains poorly understood. Marked fluctuations of alertness and of the cognitive performances, moderate parkinsonism and episodes of visual hallucinations may lead to suspect this diagnosis in cases of dementia. Unexplained falls, syncopes, delirium or alterations of consciousness may also be observed, and the patients may then be admitted in departments of internal medicine or geriatrics. The Lewy body is an intraneuronal spherical inclusion, present in Parkinson's disease. It is observed in the brainstem (substantia nigra, locus coeruleus, dorsal nucleus of the Xth nerve) and in the nucleus basalis of Meynert. The cortical Lewy bodies have a different aspect, but retain their antigenic characteristics: they are, in particular, stained by the antiubiquitin antibodies. Recently, they were found to be also labeled by antisynuclein antibodies. A mutation of the synuclein gene was recently identified in cases of familial Parkinson's disease. Clinically as well as pathologically, DLB may thus be difficult to distinguish from Alzheimer's disease on the one hand, and from Parkinson's disease, on the other. That diagnosis, however, is associated with a poor prognosis and should lead to specific therapeutic measures.     

Probable dementia associated with Lewy body pathology as a cause of prolonged acute confusional state in a 79-year-old patient

Differentiation of "dementia with Lewy body pathology" (DLB) and delirium may be problematic in some cases, due to some of their common clinical characteristics such as fluctuations and hallucinations. Longer duration of cognitive changes usually aids in DLB diagnosis. However, presentation of DLB with an abrupt onset as a prolonged confusional state and hallucinations is also, even if rarely, described. We report the case of an elderly patient with probable dementia with Lewy body pathology, presenting with a prolonged acute confusional state, in order to draw attention to its diagnostic difficulty and the importance of careful target-oriented anamnesis in such cases. This type of dementia should be included in the differential diagnosis of elderly patients presenting with otherwise unexplained prolonged acute confusional states.     

Behavioral and psychological symptoms in dementia with Lewy-bodies (DLB): frequency and relationship with disease severity and motor impairment

Clinical criteria for DLB have been more and more accurate over time, and they had focused on psychotic symptoms for their high frequency. Recent literature suggests that behavioral and psychological symptoms of dementia (BPSD) are frequently associated with DLB, beyond the presence of psychosis. Notwithstanding, the occurrence of BPSD in DLB is under-investigated, and no data are available yet in the different stages. Aim of the present study was to evaluate BPSD pattern in the different stages of DLB, and characterize the relationship with both cognitive deficits and Parkinsonian signs. Ninety-two DLB patients were enrolled and were divided into mild (n=63, 68.5%) and moderate-severe (n=29, 31.5%) subgroups according to the severity of cognitive impairment. Considering the absence/presence of symptoms, anxiety was the most common BPSD (67.4%), followed by depression (61.9%), apathy (57.6%), agitation and sleep disorder (55.4%). Psychosis was present in half of the patients. These symptoms worsened over disease course and represented a core-feature of the disease. No association between BPSD severity and the degree of motor disability was found. These observations suggest that a careful and systematic evaluation of BPSD is mandatory for carefully characterizing disease-related features and for developing new therapeutic approaches. Knowledge of the specific weight of BPSD in DLB would contribute to improve the allocation of health resources for dementia and to a better management of the disease.     

Sensitivity of SPECT for the Diagnosis of Alzheimer's Disease

Abstract

The objective of this study was to define the technical and clinical variables which affect the sensitivity of single photon emission computed tomography (SPECT) for the diagnosis of Alzheimer's disease (AD). This was a retrospective analysis of 250 consecutive SPECT studies performed for the diagnostic evaluation of degenerative dementia or memory disorder. The sensitivity of bilateral temporoparie-tal perfusion defects for probable AD cases was not affected by age, education, or technical factors such as the interpreting radiologist, type of radionuclide, and use of a ring detector system. Sensitivity increased with severity of dementia and duration of disease. Sensitivity also increased with male gender due to a higher prevalence of unilateral defects in women with probable AD. This gender effect was absent if unilateral temporoparietal defects were considered diagnostic of AD. Due to the high prevalence of AD, the most common outcome of SPECT in this series was to confirm the clinical diagnosis of AD; however, SPECT may be of greatest value for ruling in a diagnosis of AD in questionable or early dementia cases. For this purpose, the maximum yield of positive diagnosis came from examination of those who had dementia symptoms greater than one year and those who were male.     

An ultrasensitive assay for diagnosis of Alzheimer's disease

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia. Aging is among the most significant risk factors. Today, AD can be diagnosed with certainty only post mortem, detecting insoluble beta-amyloid peptide (Abeta) aggregates in the patient's brain tissue. We have developed an ultrasensitive assay for early and non-invasive diagnosis of AD. This highly specific and sensitive assay uses fluorescence correlation spectroscopy (FCS) and is sensitive enough to detect even single aggregates in body fluids of AD patients. We investigate the correlation of aggregated Abeta concentrations in body fluids with clinical symptoms of AD.     

Alzheimer's disease. Accurate and early diagnosis in the primary care setting

Alzheimer's disease is the most common dementia type and is characterized by a gradual, progressive decline in multiple areas of cognition and function. Early diagnosis is key because it can initiate the process of patients and family adapting to and managing disease symptoms. Moreover, certain pharmacologic interventions can impede symptom progression and significantly improve quality of life. A spectrum of basic tests and instruments make clinical diagnosis of AD attainable in the primary care setting. Treatment with cholinesterase inhibitors is targeted toward cognitive enhancement. Neuroprotection involves delaying dementia progression and remains experimental. Problematic cases should be referred.     

The role of routine laboratory studies and neuroimaging in the diagnosis of dementia: a clinicopathological study

OBJECTIVE: To determine the neuropathological diagnoses of longitudinally followed patients with potentially reversible causes of dementia and to examine the results of the "dementia work-up," especially neuroimaging, by comparison with the pathological diagnosis. DESIGN: A neuropathologic series of 61 consecutive patients, with review of clinical, laboratory, neuroimaging, and pathological results. RESULTS: Of the 61 patients, forty-eight (79%) had a clinical diagnosis of probable or possible Alzheimer's disease (AD). Compared with the pathological diagnosis, the sensitivity and specificity of the clinical diagnosis of AD were 96% and 79%, respectively. Of the 61 patients, 9 had abnormal laboratory tests, the correction of which did not improve the subsequent course. These patients were found to have AD8 and frontotemporal dementia on pathology. In two patients, neuroimaging was helpful in the clinical diagnoses of frontotemporal dementia and progressive supranuclear palsy (PSP). Neuroimaging revealed cerebrovascular disease in 18 patients, only two of whom were suspected clinically. Pathology confirmed AD in 17 and PSP in 1 of these patients. Sensitivity and specificity for the clinical diagnosis of cerebrovascular disease in comparison with pathology were 6% and 98%, respectively. With the added information from neuroimaging, that sensitivity increased to 59% and specificity decreased to 81%. CONCLUSIONS: All cases with abnormal laboratory or neuroimaging results had AD or some other neurodegenerative disease on pathology. The "dementia work-up" did not reveal any reversible causes for dementia in this group of patients. Neuroimaging may have a role, especially in the diagnosis of possible AD with concomitant cerebrovascular disease.     

Serum amyloid A in Alzheimer's disease brain is predominantly localized to myelin sheaths and axonal membrane

Immunohistochemical localization of the injury specific apolipoprotein, acute phase serum amyloid A (A-apoSAA), was compared in brains of patients with neuropathologically confirmed Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), Pick's disease (Pick's), dementia with Lewy bodies (DLB), coronary artery disease (CAD), and schizophrenia. Affected regions of both AD and MS brains showed intense staining for A-apoSAA in comparison to an unaffected region and non-AD/MS brains. The major site of A-apoSAA staining in both diseases was the myelin sheaths of axons in layers V and VI of affected cortex. A-apoSAA contains a cholesterol binding site near its amino terminus and is likely to have a high affinity for cholesterol-rich myelin. These findings, along with our recent evidence that A-apoSAA can inhibit lipid synthesis in vascular smooth muscle cells suggest that A-apoSAA plays a role in the neuronal loss and white matter damage occurring in AD and MS.     

Serum amyloid A in Alzheimer's disease brain is predominantly localized to myelin sheaths and axonal membrane.

Immunohistochemical localization of the injury specific apolipoprotein, acute phase serum amyloid A (A-apoSAA), was compared in brains of patients with neuropathologically confirmed Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD); Pick's disease (Pick's), dementia with Lewy bodies (DLB), coronary artery disease (CAD), and schizophrenia. Affected regions of both AD and MS brains showed intense staining for A-apoSAA in comparison to an unaffected region and non-AD/MS brains. The major site of A-apoSAA staining in both diseases was the myelin sheaths of axons in layers V and VI of affected cortex. A-apoSAA contains a cholesterol binding site near its amino terminus and is likely to have a high affinity for cholesterol-rich myelin. These findings, along with our recent evidence that A-apoSAA can inhibit lipid synthesis in vascular smooth muscle cells suggest that A-apoSAA plays a role in the neuronal loss and white matter damage occurring in AD and MS.     

Clinical findings, functional abilities and caregiver distress in the early stage of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD)

Few studies have compared neuropsychiatric disorders and functional abilities in the early stage of DLB and AD and their influence on caregiver distress. The aim of this study is to assess neuropsychiatric disorders, functional abilities and caregiver distress in DLB and in AD subjects. Sixteen subjects affected by probable DLB and 12 subjects affected by probable AD were enrolled. All subjects underwent a wide neuropsychological examination. Caregiver's distress was also assessed. Subjects affected by DLB performed better in long-term memory tests, whereas AD subjects performed better in attentive and executive function tests. The Neuropsychiatric Inventory (NPI) total score was significantly higher in DLB subjects than in AD subjects. Furthermore, DLB subjects scored worse than AD subjects in both Activities of Daily Living scale (ADL) and Instrumental Activities of Daily Living scale (IADL) scales. Overall caregiver distress was higher in DLB than in AD subjects. High distress was observed in DLB caregivers alone and was caused by delusion, hallucinations, anxiety and apathy. DLB subjects have a different neuropsychological profile, more psychiatric symptoms and more serious functional deficits than AD subjects in the early cognitive decline, furthermore DLB caregivers are more stressed than AD caregivers.     

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB), the second most frequent cause of primary degenerative dementias following Alzheimer's disease, has been increasingly recognized since the proposal of the consensus name and clinical diagnostic criteria. Although DLB overlaps in clinical, pathological, and genetic features with Alzheimer's disease and Parkinson's disease, DLB should be understood as an entity with the essential feature of the presence of Lewy bodies in the brain stem and cerebral cortex. From the clinical point of view, DLB is characterized by the presence of progressive dementia without severe memory disorders at the early stage, with significant cognitive fluctuations, well-formed recurrent visual hallucinations, and spontaneous Parkinsonism. This article reviews recent clinical and research findings, including our own, to facilitate clinical recognition of DLB. In addition to the supportive features described in the consortium clinical diagnostic criteria for DLB such as falls and great sensitivity to neuroleptic drugs, our studies found other frequent disorders including disproportionately severe visuoconstructive and visuoperceptual disturbances, transitory alterations in consciousness with reduplication phenomena, misidentification delusions, and non-aphasic misnamings. Neuroimaging features include relatively preserved hippocampal volume on MRI and occipital involvement on metabolic and blood flow imagings. The correct diagnosis of DLB is important to administer adequate treatment, to avoid adverse effects with neuroleptic drugs, and to establish precise prognosis. The present summary of the clinical features is hopefully helpful for clinical diagnosis of DLB. From a therapeutic point of view, cholinesterase inhibitors seemingly show some efficacy in the treatment of cognitive alterations. Further research would result in advances in diagnostic methods and therapeutic approaches in the near future.