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PubMed1986

Neuropsychological performance in dementia of the Alzheimer type and multi-infarct dementia.

Neuropsychological performance was examined in patients with dementia of the Alzheimer type (DAT) and in age- and education-matched patients with multi-infarct dementia (MID). Significant differences were observed for FSIQ, VIQ, and Picture Completion. This contrasts to no difference in verbal memory, visual-spatial skills, and sustained attention/concentration. This report illustrates that neuropsychological testing of elderly patients is unable to aid in the differential diagnosis between clinically similar forms of dementia, and should be employed to establish the level of cognitive function to make inferences regarding the patient's functional independence.

Journal Article↗
PubMed2004

[Parkinson disease with dementia--responsible locus for dementia].

Responsible locus for dementia in Parkinson disease (PD) was investigated. Serial 1,395 autopsy cases were studied for the combined pathology of PD and Alzheimer disease (AD). Following the one-year rule by the first Consensus Guidelines, definite AD pathology was quite rare in PD with dementia (PDD) but common in dementia with Lewy bodies (DLB) . Plaque-dominant senile changes apparently enhanced neocortical Lewy-body pathology in both the conditions. About the hypometabolism in the visual cortex of PDD, a 66-year old man presented with fluctuation in hallucination commensurate with fluctuating hypometabolism. Considering the paucity in pathological changes of the visual cortex, this hypometabolism may represent functional impairment in the fiber connection. Comparative pathological studies with PD and PDD were carried out. Only one case of a 48-year-old woman, who unexpectedly died of heart failure, was free from cognitive decline, and did not show limbic and neocortical involvement. Another case of a 75-year old man with MCI presented with the similar pathology. All other cases showed clinical documentation of cognitive impairment and limbic and neocortical pathological involvement. Thus, the combination of prospective clinical and radiological studies and retrospective pathological studies (dynamic neuropathology) may be essential to investigate a role of the basal-forebrain cholinergic system.

Aged↗
PubMed2005

Dementia with Lewy bodies: a commonly unrecognized cause of dementia.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia of the elderly following Alzheimer's disease. The significant clinical features include: fluctuating cognition with pronounced variations in attention and alertness, recurrent visual hallucinations, and spontaneous motor features of parkinsonism. As an alpha-synucleinopathy, DLB is characterized by Lewy bodies of both classical and cortical types with neuritic degeneration. This report describes an autopsy of an elderly woman with DLB and reviews the clinical and pathologic features of dementia with Lewy bodies.

Aged↗
PubMed1997

A population-based analysis of qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type: implications for individuals with questionable dementia.

Qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type (DAT) were examined in a population-based study. Qualitative error scores were derived from measures of verbal and figural memory, verbal fluency and confrontation naming for 38 patients with clinically diagnosed DAT, 236 normal elderly (NE) individuals, and 72 others who were questionably demented and at risk (AR) for DAT. Persons with DAT made a greater proportion of intrusion and perseverative errors, and more lexical and semantic naming errors, than the NE participants. These measures provided fair specificity but poor sensitivity for the diagnosis of DAT, and a logistic model based on these measures correctly classified 98% of the NE participants, but only 29% of the DAT participants. The AR participants demonstrated a pattern of errors that was highly similar to that of the DAT patients, and when their scores were subjected to the logistic model, 90% were classified as NE and 10% as DAT. These results indicate that specific error types that have been associated with DAT in self-referred or clinic-based samples also occur in the general population to a greater degree in individuals with DAT or questionable dementia than in NE individuals. Furthermore, these qualitative features may have some diagnostic usefulness in that their presence provides reasonable specificity for DAT or questionable dementia.

Aged↗
PubMed2001

Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease.

An international group of clinical and basic scientists participated in the Frontotemporal Dementia and Pick's Disease Criteria Conference at the National Institutes of Health in Bethesda, Md, on July 7, 2000, to reassess clinical and neuropathological criteria for the diagnosis of frontotemporal dementia (FTD). Previous criteria for FTD have primarily been designed for research purposes. The goal of this meeting was to propose guidelines that would enable clinicians (particularly neurologists, psychiatrists, and neuropsychologists) to recognize patients with FTD and, if appropriate, to expedite their referral to a diagnostic center. In addition, recommendations for the neuropathological criteria of FTD were reviewed, relative to classical neuropathology and modern molecular biology.

Adult↗
PubMed1993

The urate and xanthine concentrations in the cerebrospinal fluid in patients with vascular dementia of the Binswanger type, Alzheimer type dementia, and Parkinson's disease.

We determined the urate and xanthine concentrations in the cerebrospinal fluid (CSF) in patients with vascular dementia of the Binswanger type (VDBT), Alzheimer type dementia (ATD), and Parkinson's disease (PD). We found that the urate concentration was significantly increased in VDBT patients, but significantly decreased in ATD patients compared with controls. The ratio of the concentrations of uric acid (UCSF) to xanthine (XCSF) in the CSF (UCSF/XCSF) had a significant correlation with the ratio of the UCSF to the urate concentration in serum (U(serum)) (UCSF/U(serum)) in ATD and PD, whereas UCSF/U(serum) increased independently of UCSF/XCSF in VDBT. We concluded that the significant increase in the urate concentration in VDBT is mainly due to an impairment of the blood-brain barrier (BBB), and its significant reduction in ATD may reflect impaired brain metabolism.

Aged↗
PubMed2001

Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia.

OBJECTIVES: The study aimed to increase understanding of behavioural changes in frontotemporal dementia (FTD) and identify features that best differentiate FTD from Alzheimer's disease (AD) and cerebrovascular dementia (CvD). METHODS: A semi-structured questionnaire was administered to carers of 30 FTD, 75 AD and 34 CvD patients. RESULTS: Behavioural changes that strongly discriminated FTD from AD and to a lesser extent CvD were loss of emotions and insight, selfishness, disinhibition, personal neglect, gluttony and sweet food preference, wandering, motor and verbal stereotypies, loss of pain, echolalia and mutism. Irritability, hyposexuality and hypersomnia did not discriminate. Emotional, eating and stereotyped behaviours correctly classified 95% of patients using regression analysis. CONCLUSIONS: Behavioural characteristics accurately differentiate FTD from AD and CvD. The findings highlight the particular importance of affective change in FTD, and underline the role of the frontotemporal lobes in emotion.

Adult↗
PubMed2004

Retrograde amnesia in dementia: comparison of HIV-associated dementia, Alzheimer's disease, and Huntington's disease.

Remote memory was assessed in persons with HIV-associated dementia (HIV-D), probable Alzheimer's disease (AD), and Huntington's disease (HD) and in healthy controls. The clinical groups were similar in overall dementia severity. Each clinical group exhibited impairments on remote memory tests relative to controls; however, temporally graded memory loss with selective preservation of older information was observed in the AD group but not the HD or HIV-D group. Analysis of cued retrieval indicated a preferential cuing benefit for the HIV-D and HD groups relative to the AD group. The similar pattern of remote memory performance demonstrated by the HIV-D and HD groups is a novel finding and suggests a subcortically mediated retrograde amnesia in HIV-D. The temporally graded pattern and the abnormal cued retrieval performance in the AD group are consistent with a consolidation deficit associated with extrahippocampal (cortical) and hippocampal damage.

AIDS Dementia Complex↗
PubMed2001

Frontal lobe dementia with novel tauopathy: sporadic multiple system tauopathy with dementia.

We present a novel tauopathy in a patient with a 10-yr history of progressive frontal lobe dementia and a negative family history. Autopsy revealed mild atrophy of frontal and parietal lobes and severe atrophy of the temporal lobes. There were occasional filamentous tau-positive inclusions, but more interesting were numerous distinctive globular neuronal and glial tau-positive inclusions in both gray and white matter of the neocortex. Affected subcortical regions included substantia nigra, globus pallidus, subthalamic nucleus, and cerebellar dentate nucleus, in a distribution similar to progressive supranuclear palsy (PSP), but without significant accompanying neuronal loss or gliosis. Predominantly straight filaments were detected by electron microscopy (EM), while other inclusions were similar to fingerprint bodies. No twisted ribbons were detected. Immuno-EM studies revealed that only the filamentous inclusions were composed of tau. Immunoblotting of sarkosyl-insoluble tau revealed 2 major bands of 64 and 68 kDa. Blotting analysis after dephosphorylation revealed predominantly 4-repeat tau. Sequence analysis of tau revealed that there were no mutations in either exons 9-13 or the adjacent intronic sequences. The unique cortical tau pathology in this case of sporadic multiple system tauopathy with dementia adds a new pathologic profile to the spectrum of tauopathies.

Aged↗
PubMed1989

Oxiracetam in the treatment of multi-infarct dementia and primary degenerative dementia.

Oxiracetam is a recently synthesized nootropic that was tested as a potential treatment for cognitive decline in patients with multi-infarct dementia (MID) and primary degenerative dementia (PDD). Subjects were 34 MID patients and 39 PDD patients who met entrance criteria for the study. A repeated measures ANOVA showed significant improvement in both patients with MID and patients with PDD for word fluency. The total score on the Relatives' Assessment of Global Symptomatology-Elderly showed significant improvement for patients with PDD. The average score on the Instrumental Activities of Daily Living Scale, however, showed a significant decline for patients with PDD.

Activities of Daily Living↗
PubMed2000

Preclinical psychopharmacology of AIDS-associated dementia: lessons to be learned from the cognitive psychopharmacology of other dementias.

Following a brief discussion of the epidemiology, underlying neuropathological mechanisms, neuropsychological symptoms and present treatment strategies of AIDS-associated dementia (AAD), parallels are drawn between the longer standing research on drugs for the treatment of other cognitive disorders, particularly senile dementia, and ongoing efforts to develop psychopharmacological approaches for the treatment of the cognitive impairments in AAD. Important aspects of hypotheses designed to guide such a research are indicated with the help of a speculative, paradigmatic hypothesis concerning the role of cortical cholinergic inputs in AAD. Furthermore, aspects of validity of animal models, and cognition as a crucial intervening variable in the effects of potential treatments, are evaluated.

AIDS Dementia Complex↗
PubMed1997

Effects of apolipoprotein E on dementia and aging in the Shanghai Survey of Dementia.

We investigated the status of the apolipoprotein E allele in 538 participants in the incidence phase of the ongoing Shanghai Survey of Dementia, including 103 demented subjects, 72 with mild cognitive impairment and 363 cognitively normal. The apo E epsilon 4 allele was present in 10.2% of control subjects and the allelic frequency did not change between ages 60 to 96 years. The apo E epsilon 4 allelic frequency was increased both in those wiht Alzheimer's disease (AD) (25.4%) and those with vascular dementia (VaD) (22.2%), but not in those with other dementing illnesses or the cognitively impaired. All of the subjects homozygous for apo E epsilon 4 were demented, three were diagnosed as having AD, and three met NINDS/AIREN criteria for VaD. The increased apo E epsilon 4 allelic frequency in clinically diagnosed VaD patients suggests that some of the infarcts are secondary to congophilic angiopathy. The adjusted odds ratio of developing AD in this community-derived study for persons with at least one apo E epsilon 4 allele was 4.1 (95% CI: 2.2, 7.7). Thus, the apo E epsilon 4 risk of developing AD in this Chinese cohort is similar to that in western community studies.

Age Factors↗
PubMed1988

Vascular dementia and dementia of the Alzheimer type. Cognition, ventricular size, and leuko-araiosis.

Multi-infarct dementia (MID) and dementia of the Alzheimer type (DAT) were compared with regard to ventricular size and leuko-araiosis (LA) on computed tomographic scans. Ninety-seven percent of patients with MID and 55.5% of patients with DAT had evidence of LA. The severity of LA was scored with a 0 through 4 rating system, and LA was found to be significantly more severe in patients with MID than in patients with DAT. Patients with MID, but not those with DAT, exhibited correlations between enlargement of the third and lateral ventricles and severity of cognitive impairment.

Aged↗
PubMed1998

CANDID--Counselling and Diagnosis in Dementia: a national telemedicine service supporting the care of younger patients with dementia.

OBJECTIVES: To audit and evaluate the introduction of a novel support service for younger people with dementia, their families and the professionals caring for them. DESIGN: A retrospective review of all calls received by a telephone helpline over a 2-year period. SETTING: CANDID (Counselling and Diagnosis in Dementia) offers direct access, by telephone and e-mail, to specially trained nurse/counsellors who record the caller's query, provide emotional support and practical advice. In addition to general advice, clinical details are held for patients registered with the service so that the advice given can be tailored to the patient's specific need and routed via the general practitioner for action. Advice is reviewed by a consultant neurologist and psychiatrist. SUBJECT: Callers to the CANDID helpline, who made a total of 1,121 calls. MAIN OUTCOME MEASURES: Details of the caller and of the patient they were caring for. Reason for calling and advice given to the caller RESULTS: Of the 1,121 calls received during the first 2 years of operation, 547 were 'registered' calls relating to 241 individual patients where more specific advice could be given through the GP. The remaining 574 'generic' calls were from members of the public and healthcare professionals who had heard about the service and were seeking information and advice. Reasons for calls were divided into three broad categories: general information; clinical advice; and advice on social issues. Among the registered callers, 50% of calls were for clinical advice. Letters were sent to GPs on 67 occasions; 48 (56%) provided information only for the GP, 16 (24%) advised a secondary referral and eight (12%) advised on the use of specific medication. CONCLUSION: The service has become rapidly accepted and used by families of patients and members of the public. Healthcare professionals have made less use of the service than anticipated, but it is hoped that this will increased as information about the service becomes disseminated.

Adolescent↗
PubMed2004

Pentagon drawing and neuropsychological performance in Dementia with Lewy Bodies, Alzheimer's disease, Parkinson's disease and Parkinson's disease with dementia.

OBJECTIVES: Early and accurate diagnosis of Dementia with Lewy Bodies (DLB) to allow the appropriate clinical treatment is a priority, given reports of severe neuroleptic sensitivity and a preferential response to cholinesterase inhibitors in these patients. There have been suggestions that constructional apraxia is prevalent in DLB, and may provide a sensitive marker of the disease. METHODS: This study examined the pentagon drawings of 100 DLB patients, 50 Alzheimer's disease (AD) patients, 81 Parkinson's disease (PD) patients of whom 36 suffered from dementia (PDD). Performance on this task was correlated with cognitive performance on the MMSE and CAMCOG scales. RESULTS: Patients with DLB were found to draw significantly worse pentagons than those with AD or PD, but not those with PDD. Drawing scores were significantly correlated with MMSE scores for the AD and PDD groups but not those with DLB. More detailed analysis of the neuropsychological correlates of constructional performance for patients with AD and DLB, revealed that those with AD showed a broad cognitive basis to their impairment, in DLB drawing was linked only to perception and praxis. CONCLUSIONS: This study has suggests that DLB subjects show an impairment of pentagon copying that is dissociable from more global cognitive impairments, whereas PD patients are relatively unimpaired on pentagon copying and AD and PDD patients show a linkage of their impairment in copying with more global cognitive deficits.

Aged↗
PubMed2005

A comparison of the efficacy of donepezil in Parkinson's disease with dementia and dementia with Lewy bodies.

BACKGROUND: Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) overlap in phenomenology and neurochemical deficits. We hypothesised they would not differ in their response to the cholinesterase inhibitor donepezil. METHODS: We recruited 70 subjects, 30 DLB and 40 PDD, in an open label study to compare the efficacy of donepezil in these two patient groups. They were assessed at baseline, 4, 12 and 20 weeks. The main outcome measures were the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and motor sub-section of the Unified Parkinson's Disease Rating Scale (UPDRS III). RESULTS: PDD patients were younger than DLB and had more severe parkinsonism at baseline. The groups were similar on all other variables of interest. By 20 weeks the mean MMSE score increased by 3.9 points in the DLB group and by 3.2 points in PDD. The mean NPI score reduced by 14.6 points for DLB and 12.0 points for PDD. These treatment effects were all significant compared to baseline (p < 0.001) but there were no significant between-group treatment differences (MMSE p = 0.56, NPI p = 0.39). UPDRS III motor scores did not change significantly from baseline values in either group. Although adverse effects were common (69%) they were usually mild and 64 patients (91%) completed the study. The four patients who did withdraw with adverse effects all had a PDD diagnosis. CONCLUSIONS: Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.

Age Factors↗
PubMed2002

Can clock drawing test help to differentiate between dementia of the Alzheimer's type and vascular dementia? A preliminary study.

OBJECTIVES: the purpose of this preliminary study was to determine if clock drawing performance may help to differentiate between dementia of the Alzheimer's type (DAT) and vascular dementia (VD) patients. METHODS: eighty-eight community-dwelling outpatients were comprehensively evaluated and met DSM-IV criteria for DAT or VD. Cognitive evaluation included the Mini-Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). CAMCOG derived clock drawings were blindly evaluated by the same investigator, according to Freedman's method for clock drawing, and a total score as well as subscores (contour, numbers, hands and center) were determined. RESULTS: There were no significant differences between DAT and VD patients in terms of demographic (age, gender, education) and cognitive (MMSE score, CAMCOG score) characteristics. On the average, the VD group showed slightly poorer performance on each of the clock drawing test (CDT) measures studied. With application of the Bonferroni correction, only Freedman's total score and hands subscore were statistically different between groups (p<0.003, p<0.004, respectively). Stepwise logistic regression analyses showed that the only significant variable was Freedman's total score (B=-0.273, p=0.005). Stepwise discriminant analysis identified Freedman's total score as the only significant predictor of diagnosis (Wilkes' lambda=0.903, p=0.003). This model correctly classified 65.9% overall into the respective DAT and VD groups. CONCLUSIONS: CDT scored according to a comprehensive technique may be of value in differentiating DAT from VD patients. We hypothesize that the classificatory ability of Freedman's method might be attributed to its presumed sensitivity to impaired executive functioning which is more pronounced in VD compared with DAT patients.

Aged↗
PubMed2003

What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia.

BACKGROUND: This open label study was designed to assess the effects of donepezil treatment, its withdrawal and subsequent recommencement on cognitive functioning, behaviour and parkinsonian symptoms in patients with probable dementia with Lewy bodies (DLB) and with Parkinson's disease who subsequently developed dementia (PDD). METHODS: Eight patients with DLB and 11 with PDD were treated with up to 10 mg of donepezil daily for 20 weeks followed by a 6-week withdrawal period. The primary outcome measures were the Mini-Mental State Examination (MMSE), the total Neuropsychiatric Inventory (NPI) and the Unified Parkinson's Disease Rating Scale III. Testing was conducted before dosing, at week 20, at a withdrawal visit and 3 months after recommencement on donepezil. RESULTS: Patients with DLB and PDD showed a significant improvement in cognition with treatment, loss of this improvement on withdrawal and restoration of treatment gains on recommencement. Both groups also demonstrated favourable, behavioural changes with treatment, PDD patients in particular deteriorating significantly after withdrawal. The only NPI symptom domain that showed a consistent significant response to both treatment (positive) and withdrawal (negative) was hallucinations. The medication was well tolerated and parkinsonian features did not alter significantly over the testing sessions. CONCLUSIONS: Our results suggest that treatment with donepezil improves cognition and hallucinations without increasing parkinsonian symptoms, and its sudden withdrawal is usually detrimental, producing acute cognitive and behavioural decline. Although recommencement on donepezil appears to reverse this deterioration we do not advise its abrupt discontinuation in this population.

Cholinesterase Inhibitors↗