The correct answer is 2 because it presents the case with the typical symptoms of dementia due to Lewy bodies, being the guiding symptom visual hallucinations. Progressive cognitive impairment, parkinsonian motor signs (inferred from clumsiness of movements) and hypersensitivity to neuroleptics even in small doses are also mentioned.

The [HIDDEN] because it presents the case with the typical symptoms of dementia due to Lewy bodies, being the guiding symptom visual hallucinations. Progressive cognitive impairment, parkinsonian motor signs (inferred from clumsiness of movements) and hypersensitivity to neuroleptics even in small doses are also mentioned.

A 76-year-old man consults for cognitive impairment, slowness and clumsiness of movements, of eight months of evolution. The family reports that the patient had visual hallucinations, so his primary care physician prescribed low doses of risperidone, with a significant worsening of motor status. In view of these data, what is the most likely diagnosis?

Unusual features of Creutzfeldt-Jakob disease followed-up in a memory clinic.

Sporadic Creutzfeldt-Jakob disease (sCJD) generally manifests itself by cognitive or rapidly progressive motor symptoms. An atypical onset or an unusual evolution may delay the diagnosis. Among patients with a confirmed diagnosis of sCJD following a post-mortem neuropathological examination at the Neuropathology Centre of Lille, France, those who had presented with atypical cognitive disorders at onset were included in the study. Four patients were included. The first patient (64-years-old) presented early language disorders, later accompanied by apathy and behavioral disorders. The prolonged course suggested a diagnosis of progressive primary aphasia. The second patient (68-years-old) presented with aphasia, apraxia, and ataxia of the right upper limb with parkinsonian syndrome, suggesting corticobasal degeneration. In the two last patients (58- and 61-years-old), the onset was marked by an anxiety-depression syndrome, falls, visual hallucinations, extra-pyramidal syndrome, and fluctuating cognitive decline. The diagnosis raised was probable Lewy body dementia. The 14.3.3 protein was found in two of the four cases. The clinical elements found may initially suggest focal atrophy or Lewy body dementia. A very rapid clinical deterioration generally suggests sCJD, but in the last case, the evolution was particularly slow. The diagnosis of sCJD must be considered in cases of rapid-onset dementia, even if all of the clinical criteria are not present. The detection of the 14.3.3 protein and multifold increase in total-Tau with normal or slightly increased phosphorylated-Tau in the CSF are additional arguments to reinforce the diagnosis. The post-mortem neuropathological examination is important to confirm the diagnosis.

[Frontal dementia or dementia praecox? A case report of a psychotic disorder with a severe decline].

Many authors have described these last years the difficulty to establish a differential diagnosis between schizophrenia and frontotemporal dementia. However treatment and prognosis of these two separate diseases are not the same. Schizophrenia is a chronic syndrome with an early onset during teenage or young adulthood period and the major features consist of delirious ideas, hallucinations and psychic dissociation. However a large variety of different symptoms describes the disease and creates a heterogeneous entity. The diagnosis, exclusively defined by clinical signs, is then difficult and has led to the research of specific symptoms. These involve multiple psychological processes, such as perception (hallucinations), reality testing (delusions), thought processes (loose associations), feeling (flatness, inappropriate affect), behaviour (catatonia, disorganization), attention, concentration, motivation (avolition), and judgement. The characteristic symptoms of schizophrenia have often been conceptualised as falling into three broad categories including positive (hallucination, delision), negative (affective flattening, alogia, avolition) and disorganised (poor attention, disorganised speech and behaviour) symptoms. No single symptom is pathogonomonic of schizophrenia. These psychological and behavioural characteristics are associated with a variety of impairments in occupational or social functioning. Cognition impairments are also associated with schizophrenia. Since the original clinical description by Kraepelin and Bleuler, abnormalities in attentional, associative and volitional cognitive processes have been considered central features of schizophrenia. Long term memory deficits, attentional and executive dysfunctions are described in the neurocognitive profile of schizophrenic patients, with a large degree of severity. The pathophysiology of schizophrenia is not well known but may be better understood by neuronal dysfunctions rather than by a specific anatomical abnormality. Frontotemporal lobar degeneration (FTLD) is one of the most common causes of cortical dementia. FTLD is associated with an anatomical atrophy that can be generalised, with a frontotemporal or focal lobar predominance. Histologically there is severe neuronal loss, gliosis and a state of spongiosis. In a minority of case Pick cells and Pick bodies are also found. The usual clinical features of FTLD are divided in three prototypic syndromes: frontotemporal dementia (FTD), progressive non-fluent aphasia (PA) and semantic dementia (SD). FTD is the most common clinical manifestation of FTLD. FTD is first characterised by profound alteration in personality and social conduct, characterised by inertia and loss of volition or social disinhibition and distractibility. There is emotional blunting and loss of insight. Speech output is typically economical, leading ultimately to mutism, although a press of speech may be present in some overactive, disinhibited patients. Memory is relatively preserved in the early stage of the disease. Cognitive deficits occur in the domains of attention, planning and problems solving, whereas primary tools of language, perception and spatial functions are well preserved. PA is an initial disorder of expressive language, characterised by effortful speech production, phonologic and grammatical errors. Difficulties in reading and writing also occur but understanding of word meaning is relatively well preserved. In SD a severe naming and word comprehension impairment occur on the beginning in the context of fluent, effortless, and grammatical speech output. There is also an inability to recognise the meaning of visual percepts. The clinical syndromes of FTLD are associated with the brain topography of the degeneration. So considerable clinical overlap can exist between schizophrenia and FTLD and the object of the following case report is to remind the difficulty to make a differential diagnosis between these two pathologies. A 34 year old non-married man is admitted in mental health district of a general hospital for behavioural disturbances that include repeated aggressions towards his family. At initial interview visual and auditives hallucinations are described. The patient doesn't care about these abnormalities and a poverty of speech is observed. The affects, globally blunted, show some degree of sadness however. The patient's birth and early development were unremarkable. At the age of 26, the patient dismissed from his job because of poor performance and absenteeism. He spent a lot of time watching TV, showed poverty of speech and become sometimes angry and violent without an explanation. He was hospitalised for several months and a schizophrenia including predominant negative features, hallucinations and delusion was diagnosed. He was treated with bromperidol, could go back to home and was followed by a general practitioner for 8 years. The patient had a stereotyped way of life during these years with a poor communication and little activity. During the months preceding the current hospitalisation, these characteristics and avolition emphasised, urinary incontinence appeared. The patient receives risperidone 8 mg/day associated with citalopram 40 mg/day during several months of hospitalisation. No significant evolution is observed regarding apathic and stereotyped way of live. The capacity of communication remains very poor. Neurocognitive assessments reveal multiple and severe dysfunctions. Memory, executive and attentional tasks are extremely disturbed. Physical and neurological examinations reveal an isolated bilateral Babinski sign. Cerebral scanner and magnetic resonance show bifrontal atrophy and PET scan is normal. There are no significant abnormalities found on blood and urine samples and on lumbar puncture. The patient is sent to a chronic neuropsychiatric hospital and the treatment is stopped. One year later, a comparative evaluation is realised. The general clinical state shows no evolution. Neurocognitive assessments are repeated and severe dysfunctions are observed with more perseverations. A diagnosis of FTLD for this patient can be discussed regarding clinical features, neurocognitive testings and neuroradiological findings. Schizophrenia is a major differential diagnosis. Psychotic symptoms like hallucinations and age of onset are essential observations for the diagnosis of schizophrenia but can not exclude FTLD. Memory, intellectual functions, executive and attentional abilities may all be disturbed in schizophrenia and FTLD. Cerebral abnormalities well established in schizophrenia are lateral ventricles enlargements. Frontal lobar atrophy is a major argument for FTLD and is only a sporadic finding in schizophrenic populations. Schizophrenia and FTLD could be comorbid diseases by several ways. A differential diagnosis between schizophrenia and FTLD is difficult to establish. Schizophrenia is a heterogeneous disease with a large variety of cognitive dysfunctions. Neurocognitive tools may improve our knowledge of schizophrenia.

Creutzfeldt-Jakob disease: a case report and differential diagnoses.

Sporadic Creutzfeldt-Jakob disease is a rare neurodegenerative disorder of unknown etiology that causes rapidly progressive dementia. This disease is uniformly fatal and most patients die within 12 months. Clinical findings include myoclonus, visual disturbances, and cerebellar and pyramidal/extrapyramidal signs in addition to rapidly progressive cognitive and functional impairment. These findings are all non-specific and it is often difficult and challenging to diagnose premortem because of low awareness and clinical suspicion. We present a 66-year-old woman with a 5-month history of rapidly progressive dementia. After a series of extensive diagnostic examinations and continuous follow-up, she was diagnosed with probable sporadic Creutzfeldt-Jakob disease based on Centers for Disease Control and Prevention (CDC) criteria, with key findings of rapidly progressive dementia, blurry vision, extrapyramidal signs (cogwheel rigidity), and abnormal hyperintensity signals on diffusion-weighted MRI. Her symptoms progressively worsened and she died 7 months after the onset. The postmortem brain autopsy demonstrated the presence of abnormal protease-resistant prion protein by Western Blot analysis. A literature review was performed on differential diagnoses that present with rapidly progressive dementia and thereby mimic sporadic Creutzfeldt-Jakob disease. These include Alzheimer's disease, dementia with Lewy Bodies, frontotemporal dementia, meningoencephalitis, corticobasal degeneration, progressive supranuclear palsy, CADASIL, and paraneoplastic encephalomyelitis.

[A 64-year-old man with parkinsonism as an initial symptom followed by dementia associated with marked abnormal behaviours].

We report a 64-year-old man with parkinsonism as an initial symptom, which was followed by dementia and abnormal behaviours. He was well until 1985, when he was 49 years old, when he noted rest tremor in his right hand. Soon tremor appeared in his left hand as well. He was seen in our clinic and levodopa was prescribed. He was doing well with this medication, however, in 1993, he started to suffer from on-off phenomenon. He also noted visual hallucination. In 1994, he stole a watermelon and ate it in the shop. He repeated such abnormal behaviours. In 1995, he was admitted to the neurology service of Hatsuishi Hospital. On admission, he was alert and oriented. He did not seem to be demented; however, he admitted stealing and hypersexual behaviours. No aphasia, apraxia, or agnosia was noted. In the cranial nerves, downward gaze was markedly restricted. He showed masked and seborrhoic face, and small voice. No motor palsy was noted, but he walked in small steps with freezing and start hesitation. Marked neck and axial rigidity was noted. Tremor was absent except for in the tongue. No cerebellar ataxia was noted. Deep tendon reflexes were diminished. Plantar response was extensor bilaterally. Forced grasp was noted also bilaterally. He was treated with levodopa and pergolide, but he continued to show on-off phenomenon. His balance problem and akinesia became progressively worse; still he showed hypersexual behaviour problems. He also showed progressive decline in cognitive functions. In 1997, he started to show dysphagia. He developed aspiration pneumonia in July of 1998. In 1999, he developed emotional incontinence and became unable to walk. He also developed repeated aspiration pneumonia. He died on March 1, 2000. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had corticobasal degeneration. Other diagnoses entertained included dementia with Lewy bodies, diffuse Lewy body disease, and frontotemporal dementia. Majority of the participants thought that diffuse Lewy body disease was most likely. Post-mortem examination revealed marked nigral neuronal loss, gliosis and Lewy bodies in the remaining neurons. Abundant Lewy bodies of cortical type were seen wide spread in the cortical areas, but particularly many in the amygdaloid nucleus. Lewy bodies were also seen in the subcortical structures such as the dorsal motor nucleus, oculomotor nucleus, Meynert nucleus, putamen, and thalamus. What was interesting was marked neuronal loss of the pontine nuclei, demyelination of the pontocerebellar fiber, and moderate neuronal loss of the cerebellar Purkinje neurons, a reminiscent of pontocerebellar atrophy. However, the inferior olivary nucleus was intact.

Successful use of donepezil for the treatment of dementia with Lewy bodies.

To report a case of the successful use of donepezil for treatment of cognitive and noncognitive symptoms in a patient with dementia with Lewy bodies. CASE SUMARY: An 86-year-old white woman with dementia was experiencing early-onset significant fluctuation of her cognitive status, functional impairment, visual hallucinations, aggression, and parkinsonism. She was intially diagnosed with Alzheimer disease and Parkinsons disease and prescribed donepezil 5 mg/d and benztropine 1 mg twice daily. On reexamination of the case by a neurologist, the diagnoses were revised to dementia with Lewy bodies. The benztropine was discontinued, and donepezil was increased to 10 mg/d. The patient's cognitive and functional status significantly improved, as did her visual hallucinations. This case supports previous reports of the marked responsiveness of patients with dementia with Lewy bodies to acetylcholinesterase inhibitors. This may be explained by the marked cholinergic deficit observed in patients with dementia with Lewy bodies and the evidence linking cognitive as well as noncognitive symptoms to this deficit. The present case suggests that patients with dementia with Lewy bodies respond well to acetylcholinesterase inhibitors. Controlled trials are necessary to further define the role of these drugs for this disease.

The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships.

Accuracy of clinical diagnosis of dementia is increasingly important for therapeutic and scientific investigations. In this study, we examine diagnostic accuracy in a consecutive series of 228 patients referred to a specialist early-onset dementia clinic, whose brains were subsequently examined at post-mortem. Diagnosis was based on structured history, neurological examination and neuropsychological assessment, with emphasis on qualitative as well as quantitative aspects of performance. Neuroimaging provided support for but did not alter the clinical diagnosis. We set out the principles that guided diagnosis: (i) time course of illness; (ii) weighting of physical, behavioural and cognitive symptoms and signs; (iii) 'anterior' versus 'posterior' hemisphere character of cognitive change; and (iv) specificity of deficit, paying attention to the differentiation between syndromes of frontotemporal lobar degeneration and focal forms of Alzheimer's disease. Forty-two per cent of the patients had clinical diagnoses of one of the syndromes of frontotemporal lobar degeneration, the high proportion reflecting the research interests of the group. Forty-six per cent were diagnosed with Alzheimer's disease and the remaining patients, dementia with Lewy bodies, Creutzfeldt-Jakob disease, vascular or unclassified dementia. Frontotemporal lobar degeneration was identified with 100% sensitivity and 97% specificity and Alzheimer's disease with 97% sensitivity and 100% specificity. Patients with other pathologies were accurately identified on clinical grounds. Examination of subsyndromes of frontotemporal lobar degeneration showed a relatively predictable relationship between clinical diagnosis and pathological subtype. Whereas the behavioural disorder of frontotemporal dementia was associated with tau, transactive response DNA binding protein 43 and fused-in-sarcoma pathology, cases of frontotemporal dementia with motoneuron disease, semantic dementia and, with one exception, progressive non-fluent aphasia were associated with transactive response DNA binding protein 43 pathology, distinguished by ubiquitin subtyping (types B, C and A, respectively). Clinical diagnoses of progressive apraxia, corticobasal degeneration and progressive supranuclear palsy were, with one exception, associated with Pick, corticobasal and progressive supranuclear palsy subtypes of tau pathology, respectively. Unanticipated findings included Alzheimer pathology in two patients presenting with the behavioural syndrome of frontotemporal dementia and corticobasal pathology in four others with clinical frontotemporal dementia. Notwithstanding such anomalies, which serve as a reminder that there is not an absolute concordance between clinical phenotype and underlying pathology, the findings show that dementias can be distinguished in life with a high level of accuracy. Moreover, careful clinical phenotyping allows prediction of histopathological subtype of frontotemporal lobar degeneration. The principles guiding diagnosis provide the foundation for future prospective studies.

Applicability of long-term electroencephalography in pre-mortem diagnosis of Creutzfeldt-Jakob disease: A case report.

Creutzfeldt-Jakob disease accounts for more than 90% of all sporadic prion disease cases. The molecular MM2 genotype has been divided into cortical and thalamic subtypes based on structures involved and is characterized clinically by progressive dementia without ataxia or typical electroencephalography changes. Proposed diagnostic criteria for MM2 cortical type sporadic Creutzfeldt-Jakob disease include progressive dementia, cortical hyper-intensity on diffusion-weighted magnetic resonance imaging, increased cerebrospinal fluid 14-3-3 protein level, and the exclusion of other types of dementia. The presence of periodic discharges on electroencephalography in MM2 cortical type were reported in 42% of the cases. We are reporting a case of sporadic Creutzfeldt-Jakob disease cortical MM2-type presenting with rapid cognitive decline, who survived 8 months since symptom onset. Brain imaging, cerebrospinal fluid analysis, and long-term electroencephalography monitoring were obtained and diagnosis was confirmed by autopsy. Short-term electroencephalography recording, performed 5 months after symptom onset, demonstrated diffuse background slowing without epileptiform activity. Long-term video electroencephalography monitoring demonstrated generalized slowing, maximum in bilateral frontal areas, which intermittently would become rhythmic (1-2 Hz) without hemispheric predominance. If the findings do not clearly meet the proposed clinical criteria for sporadic Creutzfeldt-Jakob disease, the use of long-term electroencephalography could increase the sensitivity. We question whether the lack of the characteristic findings on electroencephalography in some cases could be due to insufficient time of recording. Application of long-term electroencephalography monitoring increases the sensitivity of electroencephalography and the certainty of pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease.

Probable Lewy Body Dementia with a Predilection for Auditory Hallucinations.

The patient was a 60-year-old male who initially presented to the emergency room with extreme agitation aggravated by internal stimuli as well as visual hallucinations, paranoia, and grandiose delusions. He was diagnosed with nonspecific schizophrenia and treated with risperidone, trazodone, and lithium. Approximately 16 months later, he was readmitted to the hospital trying to enter a stranger's car that he thought was his. He was confused and was unable to give an accurate history. His psychomotor retardation and confusion were thought to be due to risperidone. When his dose was decreased, he displayed involuntary movements of the mouth and extremities, restlessness, and a patting of his head. The risperidone was switched to zyprexa in an effort to decrease extrapyramidal symptoms. About two months later, he was found unresponsive and catatonic in his car. During his stay, the patient had a fluctuation in the latency of his responses on a daily basis. He would be aware of where he was but was unable to explain why or for how long. He had a difficult time remembering names and was still exhibiting abnormal involuntary movements around the mouth and extremities. The patient's course of initial predominantly auditory and visual hallucinations that progressed to extrapyramidal symptoms and fluctuating cognition one year later may suggest Lewy body dementia.

Creutzfeldt–Jakob disease

Signs and symptoms The first symptom of CJD is usually rapidly progressive dementia, leading to memory loss, personality changes, and hallucinations. Myoclonus (jerky movements) typically occurs in 90% of cases, but may be absent at initial onset. Other frequently occurring features include anxiety, depression, paranoia, obsessive-compulsive symptoms, and psychosis. This is accompanied by physical problems such as speech impairment, balance and coordination dysfunction (ataxia), changes in gait, and rigid posture. In most people with CJD, these symptoms are accompanied by involuntary movements. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks. Most victims die six months after initial symptoms appear, often of pneumonia due to impaired coughing reflexes. About 15% of people with CJD survive for two or more years.

Dementia with Lewy bodies

Frontotemporal dementias Corticobasal syndrome, corticobasal degeneration and progressive supranuclear palsy are frontotemporal dementias with features of parkinsonism and impaired cognition. Similar to DLB, imaging may show reduced dopamine transporter uptake. Corticobasal syndrome and degeneration, and progressive supranuclear palsy, are usually distinguished from DLB by history and examination. Motor movements in corticobasal syndrome are asymmetrical. There are differences in posture, gaze and facial expressions in the most common variants of progressive supranuclear palsy, and falling backwards is more common relative to DLB. Visual hallucinations and fluctuating cognition are unusual in corticobasal degeneration and progressive supranuclear palsy. Management

Alzheimer Society of Ireland

The Alzheimer Society of Ireland also operates the Alzheimer National Helpline, offering information and support to anyone affected by dementia on 1800 341 341. Activities The Alzheimer Society of Ireland provides services such as the Alzheimer National Helpline, Social Clubs, Support Groups, Day Care Services, Home Care, Dementia Advisor Service and the Mobile Information Bus. The charity does not exclusively help people with Alzheimer's disease. There are many types of dementia, which is an umbrella term. Dementia types include vascular dementia, dementia with Lewy bodies, frontotemporal dementia, Korsakoff's syndrome, Creutzfeldt–Jakob disease, HIV related cognitive impairment, mild cognitive impairment, and other rarer causes of dementia.

[Changeover to risperidone after treatment with conventional low potency neuroleptics in dementia patients. An observation study during usage].

Up to 90% of the patients with dementia develop behavioral and psychological symptoms during the course of their illness. Since 1999 the atypical neuroleptic risperidone is the only drug approved by the German authorities for the treatment of aggressive behavior or psychotic symptoms of dementia, which was defined in March 2004 with respect to severe chronic aggressive behavior, endangering themselves or others, or impoverishing psychotic symptoms. This prospective investigation was aimed at detecting therapeutic efficacy and the tolerability of risperidone after changing from low-potency neuroleptics in patients, for whom the broader indications before March 2004 were still valid. Symptoms, activities of daily living and caregivers" burden were documented for 6 weeks in 111 demented patients with chronic aggressive behavior and psychotic symptoms. Marked improvements of psychotic symptoms, aggressiveness, other behavioral disorders and activities of daily living were observed. Furthermore, a substantial reduction of caregivers' burden was noted. The treatment with risperidone was well tolerated. No patient died and no cerebrovascular events were observed. Changing the treatment of demented patients from low-potency neuroleptics to risperidone led to marked improvement of symptoms and to a substantial decrease of caregivers' burden.

[A clinicopathological study on 13 cases of motor neuron disease with dementia].

Thirteen patients suffering from motor neuron disease with dementia were studied to analyze the clinicopathological spectrum. The diagnosis of the disease was made on the basis of a clinical history of progressive dementia and motor neuron involvement. The mean age at onset of 11 sporadic cases was 54.9 years (range, 43 to 69 years), with a mean duration of disease of 25 months (range, 11 to 47 months). The initial symptoms were dementia in 7 cases, motor neuron involvement in 2 cases, and both dementia and motor neuron involvement in 2 cases. The clinical picture of motor neuron disturbance in sporadic cases represented bulbar-type of amyotrophic lateral sclerosis (ALS). Bulbar palsy was the initial symptom in 7 sporadic cases and all 11 patients developed bulbar palsy with advancing course of illness. Muscular wasting and fasciculation were more predominant in the upper limbs, shoulder girdle and anterior chest. Fasciculation was more extensively and frequently observed in those portions than that of classical ALS. In contrast, muscle strength in the lower limbs was well preserved so that all patients could walk even when respiratory failure developed. Hyperreflexia including jaw jerk was found in all cases and positive Babinski sign in 7 cases. Parkinsonism appeared in the initial stage in one sporadic case and in two familial cases. The type of dementia with uninhibited behavior and personality change closely mimicked that of Pick's disease. The degree of dementia was mild or moderate in 8 cases and severe in 3 cases. Language disorder was characterized by progressive reduction of speech output, leading finally to mutism in 5 cases. Perseveration was observed in 10 cases. Visuospatial disorder was absent even in the advanced stage. Mild memory disturbance was noted in the early stage in 10 cases. Pathological examination was performed in 7 cases including one familial case, revealing frontal atrophy in 3 cases, frontotemporal atrophy in 2 cases and temporal atrophy in 2 cases. On microscopic examination there were mild neuronal loss, gliosis, mild spongy state of the cortical superficial layers and fibrous gliosis in the frontotemporal white matter. The scattered senile plaques in one case did not justify a diagnosis of Alzheimer's type dementia. Neither circumscribed atrophy nor Pick body was found in any case. The nucleus basalis of Meynert showed no neuronal loss. The substantia nigra showed a mild to severe loss of nerve cells without Lewy bodies in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Alzheimer's Society

Alzheimer's Society is a United Kingdom care and research charity for people with dementia and their carers. It operates in England, Wales and Northern Ireland, while its sister charities Alzheimer Scotland and Alzheimer's Society of Ireland cover Scotland and the Republic of Ireland respectively. Despite its name, the charity does not exclusively help people with Alzheimer's disease. There are many types of dementia, which is an umbrella term. Dementia types include vascular dementia, dementia with Lewy bodies, frontotemporal dementia, Korsakoff's syndrome, Creutzfeldt–Jakob disease, HIV-related cognitive impairment, mild cognitive impairment, and other rarer causes of dementia. It is a membership organisation, which works to improve the quality of life of people affected by dementia in England, Wales and Northern Ireland. Many of the 25,000 members have personal experience of dementia, as carers, health professionals or people with dementia themselves.

Rapidly Progressive Dementia in the Outpatient Clinic: More Than Prions.

Published approaches to the evaluation and management of patients with rapidly progressive dementia (RPD) have been largely informed by experience at academic hospitals and national centers specializing in the diagnosis of Creutzfeldt-Jakob disease. Whether these approaches can be applied to patients assessed within lower-acuity outpatient settings is unknown. A total of 96 patients with suspected RPD were assessed within the Washington University School of Medicine (Saint Louis, MO) outpatient memory clinic from February 2006 to February 2016. Consensus etiologic diagnoses were established following independent review of clinical data by 2 dementia specialists. In total, 67/90 (70%) patients manifested with faster-than-expected cognitive decline leading to dementia within 2 years of symptom onset. Female sex (42/67, 63%), median patient age (68.3 y; range, 45.4 to 89.6), and years of education (12 y; range, 6 to 14) were consistent with clinic demographics. Atypical presentations of common neurodegenerative dementing illnesses accounted for 90% (60/67) of RPD cases. Older age predicted a higher odds of amnestic Alzheimer disease dementia (OR, 2.1 per decade; 95% CI, 1.1-3.8; P=0.02). Parkinsonism (OR, 6.9; 95% CI, 1.6-30.5; P=0.01) or cortical visual dysfunction (OR, 10.8; 95% CI, 1.7-69.4; P=0.01) predicted higher odds of another neurodegenerative cause of RPD, including sporadic Creutzfeldt-Jakob disease. The clinical environment influences the prevalence of RPD causes. The clinical evaluation should be adapted to promote detection of common causes of RPD, specific to the practice setting.

Dementia

Many other medical and neurological conditions include dementia only late in the illness. For example, a proportion of patients with Parkinson's disease develop dementia, though widely varying figures are quoted for this proportion. When dementia occurs in Parkinson's disease, the underlying cause may be dementia with Lewy bodies or Alzheimer's disease, or both. Cognitive impairment also occurs in the Parkinson-plus syndromes of progressive supranuclear palsy and corticobasal degeneration (and the same underlying pathology may cause the clinical syndromes of frontotemporal lobar degeneration). Although the acute porphyrias may cause episodes of confusion and psychiatric disturbance, dementia is a rare feature of these rare diseases. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a type of dementia that primarily affects people in their 80s or 90s and in which TDP-43 protein deposits in the limbic portion of the brain.

[Two new cases of sporadic Creutzfeldt-Jakob disease in Madrid, Spain].

Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy, in which there is typically an accumulation of an altered isoform of the prion protein in the brain. The sporadic form is characterised by presenting a rapidly progressive dementia, with signs and symptoms of pyramidal, extrapyramidal, cerebellar and cortical involvement, as well as the presence of myoclonias. Diagnosis is based on the clinical findings in combination with the typical results of an electroencephalogram, cerebrospinal fluid study or neuroimaging. We report two cases detected between the years 2008 and 2010 in the Hospital del Henares, in Coslada, Madrid. Case 1: a female with progressive loss of strength in her limbs, change in her behaviour with mood swings and a tendency towards seeking to isolate herself. Although initially considered a psychiatric patient, in the months that followed she became absolutely immobile with a tendency towards mutism. Death occurred six months after the onset of symptoms. Case 2: a male with a progressive picture of altered vision in the form of right homonymous hemianopia, difficulty in verbally expressing language, dizziness and instability. The patient gradually developed a cerebellar syndrome with generalised myoclonias until his death, 10 weeks after the onset of symptoms. In both cases, the electroencephalogram showed a typical pattern and 14-3-3 protein was positive in the cerebrospinal fluid study. Such a high incidence over such a short period of time and in a health district of barely 170,000 inhabitants seems rather surprising.

Corticobasal syndrome

The diagnosis is excluded if there is evidence of: Lewy body disease multiple system atrophy Alzheimer's disease amyotrophic lateral sclerosis semantic or logopenic variant primary progressive aphasia structural lesion suggestive of focal cause granulin mutation or reduced plasma progranulin levels TDP-43 or fused in sarcoma (FUS) mutations The diagnostic criteria for clinical use may result in a misdiagnosis of other tau-based diseases. The probable criteria are proposed for clinical research. Differential Other degenerative pathologies that can cause corticobasal syndrome include: Alzheimer's disease Pick's disease with Pick bodies Lewy body dementias Neurofilament inclusion body disease Creutzfeldt-Jakob disease Frontotemporal degeneration due to progranulin gene mutation Motor neuron disease‐inclusion dementia. The symptoms of classic CBS differ from CBD in that CBD also includes cognitive deficits in the executive functions. Prognosis

[Primary degeneration of the thalamus with dementia--2 cases with family background].

This is a report on two male patients aged 22 and 43 years, respectively, who developed a fatal progressive demential syndrome that lead to the death of one after 16 months and of the other patient after 25 months and that presented with the typical clinical pattern of "subcortical dementia". In both the cases, the hospital had suspected Creutzfeldt-Jacob's disease but this was not confirmed by microscopy of the tissue; the typical form of manifestation was absent. Instead, microscopy of the brain revealed a marked symmetric degeneration of the thalamus with special preference given to the anterior and media nuclear groups. Predilection for the neothalamic against the palaeothalamic and archithalamic structures produced a very strong impression of a system-related thalamic degeneration process of the type occasionally discussed on the basis of similar observations. Parallel to the atrophic process there were also degenerative changes that were less pronounced, in the rubro-olivo-cerebellar system and in one case a moderately pronounced involvement of the second motor neuron. Both observations of a "thalamic dementia" are discussed against the background of relevant literature published so far on the subject.

Dementia

The most common type of dementia is Alzheimer's disease. Other common types include vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Less common causes include normal pressure hydrocephalus, Parkinson's disease dementia, syphilis, HIV, and Creutzfeldt–Jakob disease.

[Care for patients with Pick's disease--by using their preserved procedural memory].

Pick's disease are more often complicated than Alzheimer's disease by behavioral disturbances such as social misconduct and stereotypy, that are troublesome and clinically difficult to manage. The purpose of this study was to investigate the possibility of improvement in care for patients with Pick's disease by using their presumably preserved procedural memory. Four inpatients and two outpatients with Pick's disease were studied. Case 1: A 54-year-old right-handed retired clerk presented with a 3-year history of increasing restlessness, word-finding difficulty and impaired comprehension of nominal terms. He was forced to retire from his work because of his social misconduct and incommunicability. On admission he wandered about the ward irritably, did not enter into any conversation, and destroyed all keys in the ward by putting a pencil into keyholes. Neuroradiological examination revealed circumscribed bilateral frontotemporal atrophy which was more marked on the left side. However, he has become more adaptive to the life in the ward and his expression has become peaceful since he began to play othello games with other patients and his doctors. Case 2: A 71-year-old right-handed housewife had progressively altered in her personality and behavior over 4 years. She was restless and showed striking palilalia with marked right frontotemporal atrophy when initially evaluated 2 years after her initial symptoms. Subsequently, her verbal output decreased. She ate large amounts of food and her overweight became a serious problem in her care at home. On admission she wandered about the ward irritably, ate meals of other patients, and put on a quilt on their head. However, these troublesome behavior disappeared when she was bent on knitting that was her former hobby. Case 3: A 63-year-old right handed physician presented with a 5-year history of increasing word-finding difficulty and impaired comprehension of nominal terms. His conversation was limited to continuous repetition of a few phrases. He wandered into several hospitals around his house in fixed order every day. On examination, he was mildly disinhibited and distractible with circumscribed bilateral frontotemporal atrophy which was more marked on the left side. Wandering away from home overnight necessitated admission to the hospital. In the ward he wandered about and tried to open each door restlessly and irritably. However, he has become calm and his expression has become peaceful since he was conducted to measure blood pressures of his nurses. Case 4: A 65-year-old right-handed retired office worker.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuroscience of aging

DNA damage Certain genes of the human frontal cortex display reduced transcriptional expression after age 40, and especially after age 70. In particular, genes that have central roles in synaptic plasticity display reduced expression with age. The promoters of genes with reduced expression in the cortex of older individuals have a marked increase in DNA damage, likely oxidative DNA damage. Pathological changes Roughly 20% of persons greater than 60 years of age have a neurological disorder, with episodic disorders being the most common followed by extrapyramidal movement disorders, and nerve disorders. Diseases commonly associated with old age include Multiple system atrophy Parkinson's disease Alzheimer's disease Stroke. Amyotrophic lateral sclerosis Creutzfeldt–Jakob disease Frontotemporal Dementia Dementia with Lewy bodies Corticobasal Degeneration Transient ischemic attack Vascular dementia

Low mood, visual hallucinations, and falls - heralding the onset of rapidly progressive probable sporadic Creutzfeldt-Jakob disease in a 73-year old: a case report.

Creutzfeldt-Jakob disease is a rare and rapidly fatal neurodegenerative disease. Since clinicians may see only very few cases during their professional career, it is important to be familiar with the clinical presentation and progression, to perform appropriate investigations, and allow for quick diagnosis. A 73-year-old British Caucasian woman presented with acute confusion of 2 weeks' duration on a background of low mood following a recent bereavement. Her symptoms included behavioral change, visual hallucinations, vertigo, and recent falls. She was mildly confused, with left-sided hyperreflexia, a wide-based gait, and intention tremor in her left upper limb. Initial blood tests, computed tomography, and magnetic resonance imaging of her brain showed no significant abnormality. Following admission, she had rapid cognitive decline and developed florid and progressive neurological signs; a diagnosis of prion disease was suspected. A lumbar puncture was performed; cerebrospinal fluid was positive for 14-3-3 protein, real-time quaking-induced conversion, and raised levels of s-100b proteins were detected. An electroencephalogram showed bilateral periodic triphasic waves on a slow background. The diagnosis of probable Creutzfeldt-Jakob disease was made. This case report highlights key features in the initial presentation and clinical development of a rare but invariably rapidly progressive and fatal disease. It emphasizes the importance of considering a unifying diagnosis for multifaceted clinical presentations. Although it is very rare, Creutzfeldt-Jakob disease should be considered a diagnosis for a mixed neuropsychiatric presentation, particularly with rapid progressive cognitive decline and development of neurological signs. However, to avoid overlooking early signal change on magnetic resonance imaging, it is important to take diffusion-weighted magnetic resonance imaging for all patients with neuropsychological symptoms. Importantly, early diagnosis also ensures the arrangement of suitable contamination control measures to minimize the risk of infection to health care professionals and other patients.

Pimavanserin

On June 29, 2018 the FDA approved new dosages of pimavanserin to treat hallucinations and delusions associated with Parkinson’s disease psychosis. A 34 mg capsule and 10 mg tablet formulation were approved. Previously, patients were required to take two 17 mg tablets to achieve the recommenced 34 mg dose per day. The 10 mg dose is indicated for patients also taking CYP3A4 inhibitors (eg. ketoconazole). HARMONY-Trial In a phase 3, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov number NTC03325556) pimavanserin was applicated in patients with dementia-related psychosis. The dementia was caused by Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, Parkinson's disease with dementia, or vascular dementia. The trial was stopped early for efficacy. Patients treated with pimavanserin had a relapse in 13 %, without in 28% (hazard ratio 0.35; 95 % - CI = 0.17-0.73; p= 0.005). Longer and larger trials are suggested.

Human brain

Disease Neurodegenerative diseases result in progressive damage to different parts of the brain's function, and worsen with age. Common examples include dementia such as Alzheimer's disease, alcoholic dementia or vascular dementia; Parkinson's disease; and other rarer infectious, genetic, or metabolic causes such as Huntington's disease, motor neuron diseases, HIV dementia, syphilis-related dementia and Wilson's disease. Neurodegenerative diseases can affect different parts of the brain, and can affect movement, memory, and cognition. The brain, although protected by the blood–brain barrier, can be affected by infections including viruses, bacteria and fungi. Infection may be of the meninges (meningitis), the brain matter (encephalitis), or within the brain matter (such as a cerebral abscess). Rare prion diseases including Creutzfeldt–Jakob disease and its variant, and kuru may also affect the brain.

[Reconciliating neurology and psychiatry: The prototypical case of frontotemporal dementia].

Frontotemporal degeneration (FTD) in its behavioral variant (bvFTD) is probably one of the conditions that best illustrates the links between psychiatry and neurology. It is indeed admitted that between a third and half of patients with this condition, especially in early-onset forms, receive an initial diagnosis of psychiatric disorder (depression, schizophrenia, bipolar disorder) and are then referred to a psychiatric ward. BvFTD can thus be considered a neurological disorder with a psychiatric presentation. Among psychiatric symptoms reported in this disease, psychotic symptoms (hallucinations, delusions, especially of persecution), which have long been underestimated in bvFTD and are not part of the current diagnostic criteria, are present in about 20% of cases and may be inaugural. They are particularly common in the genetic forms related to a mutation in the C9orf72 gene (up to 50%), and to a lesser extent in the GRN gene (up to 25%). C9orf72 gene mutation is often associated with a family history of dementia or motor neuron disease but also of psychiatric disorders. It has also been described in sporadic presentation forms. Sometimes, the moderate degree of brain atrophy on MRI described in patients carrying this mutation may complicate the differential diagnosis with late-onset psychiatric diseases. In the present article, we underline the importance of considering that psychiatric - especially psychotic - symptoms are not rare in bvFTD, which should lead to a revision of the diagnostic criteria of this disease by taking greater account of this fact. We also propose a diagnostic chart, based on concerted evaluation by neurologists and psychiatrists for cases of atypical psychiatric symptoms (late-onset or pharmacoresistant troubles) leading to consider the possibility of a neurological disorder, in order to shed a new light on these difficult clinical situations. In the field of research, bvFTD may constitute a model to explore the neural basis of certain psychiatric disorders, and a possible molecular link between bvFTD and psychoses, which could eventually lead to new therapeutic approaches, has been recently suggested. Thus, bvFTD illustrates how the links between neurology and psychiatry are close and tend to evolve with the progress of scientific knowledge. It is necessary to strengthen collaboration between the two disciplines both to improve the care - diagnosis and management of these patients - and to promote the emergence of innovative clinical research.

Mini-SEA

The mini-SEA (mini-Social cognition & Emotional Assessment) is a neuropsychological battery aiming to evaluate the impairment of the social and emotional cognition. Developed by Maxime Bertoux in 2012, the mini-SEA has been preferentially designed for the assessment, follow-up and diagnosis of neurodegenerative diseases such as the frontotemporal dementia, but is more generally designed to evaluate the integrity of the frontal lobes. Constituents of the mini-SEA The estimation completion time for the mini-SEA is 30 minutes. The whole battery is composed from two subtests : (1) a reduced and modified version of the Faux-Pas test, assessing Theory of Mind and (2) a facial emotions recognition test. Both tests are among the most sensitive and specific tests for the diagnosis of the frontotemporal dementia and accurately discriminate frontotemporal dementia patients from controls or patients with Alzheimer's disease. Brain regions involved

[Electro-clinical evolution of cerebral spongiosis].

Electroencephalogram was repeated about every third week in the last five months' course of a spongiform encephalopathy, Creutzfeldt-Jakob type. This confirms the interest of EEG and its diagnostic value in certain presenile dementias. The appearance of triphasic stereotyped complexes with a short periodic interval is the fundamental pattern allowing to predict, then to assess, the diagnosis. Our study is based upon 14 polygraphic records (including EEG, respiratory rhythm, ocular movements and limbs' actogram); compared with previous studies from the literature it shows some pecularities: - periodic discharges with an interval of about one second appearing early, i.e. before the clinical picture became typical, -lack of any change under the influence of various drugs and stimulations, - stability of the pattern throughout the whole course of the disease.

Rapidly progressive dementias and the treatment of human prion diseases.

Rapidly progressive dementia (RPD) has many possible etiologies and definitive treatment is reliant upon an accurate diagnosis from an appropriate diagnostic work-up. A large portion of the neurodegenerative causes of RPD are due to prion diseases (e.g., Creutzfeldt-Jakob disease). The study of prion diseases, for which there is no currently available treatment, has public health implications and is becoming increasingly more relevant to our understanding of other protein misfolding disorders including Alzheimer's disease, frontotemporal degeneration, and Parkinson's disease. This article begins with an overview of the etiologies and diagnostic work-up of RPD followed by a detailed review of the literature concerning the treatment of human prion diseases (1971 to present). The reader will understand the differential diagnosis and work-up of RPD as it pertains to its treatment, as well as an in-depth understanding of treatments of human prion diseases. An accurate diagnosis of the cause of RPD is of paramount importance when determining appropriate treatment. Most studies of the treatment for human prion diseases are case reports or case series, and results from only one randomized, placebo-controlled study have been reported in the literature (flupirtine). Studies have been hindered by disease heterogeneity and lack of standardized outcome measures. Although no effective prion disease treatment has been revealed through these studies, they provide important considerations for future studies.

Clive Ballard

---., et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology, Dec 2005, 65 (12). ---., et al. Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study. The Lancet Neurology, Volume 17, Issue 3. ---., et al. Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: A cluster-randomised controlled trial. PLOS Medicine 15(2): e1002500. ---., et al. Cognitive decline in Parkinson disease. Nature Reviews Neurology, volume 13. ---., et al. Dementia prevention, intervention, and care. The Lancet, Volume 390, Issue 10113.

Early onset dementia

Early onset dementia is dementia in which symptoms first appear before the age of 65. The term favored until about 2000 was presenile dementia; young onset dementia is also used. Early onset dementia may be caused by degenerative or vascular disease, or it may be due to other causes, such as alcohol-related dementia and other inflammatory or infectious processes. Early-onset Alzheimer's disease, vascular dementia and frontotemporal lobar degeneration are the most common forms of early onset dementia, with Alzheimer's accounting for between 30 and 40%. Early onset dementia may also occur, less frequently, in the Lewy body dementias (dementia with Lewy bodies and Parkinson's disease dementia), multiple sclerosis, Huntington's disease and other conditions. References Further reading Cognitive disorders Dementia

An Indonesian elderly with primary progressive aphasia and behavioral variant of frontotemporal dementia: A case report and review article.

Frontotemporal dementia (FTD) or Pick's disease, is the second most frequent cause of primary degenerative dementia in those between 55 and 65 years old. A 57-year-old Indonesian female reported family that six months until one year prior to the presentation of her first symptoms, the patient had problems with memory, particularly short-term memory loss, with the patient unable to remember the task she was doing on time. The electroencephalogram revealed slowing background cerebral activity and diffuse slowing activity, indicating encephalopathy diffuse moderate state. CSF showed no pleocytosis and no elevated CSF Protein, but we did not perform tau level. She underwent brain magnetic resonance imaging (MRI) because of her aggression and impulsiveness. Brain MRI was notable for bilateral frontal and temporal atrophy. Incidentally, there was the leptomeningeal enhancement of the bilateral frontotemporal lobe. The patients were administered Haloperidol 0.5 mg orally twice daily, Donepezil 5 mg oral once daily, Aripiprazole 2.5 mg once daily, and Memantine 10 mg twice daily. The patient was discharged one week after admission and was started on antiviral therapy Acyclovir 800 mg 5 times a day for 14 days. The patient had shown more cooperative and less agitative. We report that FTD aims to help improve effective management. Awareness of FTD needs to be increased even though this case is sporadic because it does not demand the possibility of this case occurring at a young age.