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PubMed2000

The Scandinavian Multi-Infarct Dementia Trial: a double-blind, placebo-controlled trial on nimodipine in multi-infarct dementia.

Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brâne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.

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PubMed2002

Vascular dementia may be the most common form of dementia in the elderly.

Cerebrovascular lesions, mainly lacunes and white matter ischemia, are common in elderly patients with dementia. Vascular dementia (VaD) is the second most common cause of dementia, after Alzheimer's disease (AD). However, lacunar strokes have become an important factor in the clinical expression of AD. Also, population-based studies indicate that vascular risk factors increase the risk of developing AD. It is postulated here that the two main causes of VaD-stroke and ischemic heart disease (IHD)-may be responsible for the majority of cases of dementia in the elderly. STROKE RELATED VaD: Cerebrovascular disease (CVD) is the second leading cause of death worldwide. About 1/3 of stroke survivors [range: 25-41%] 65 years old and above develop VaD within 3 months following the ictus. In the USA alone, 125,000 new cases/year of VaD occur after ischemic stroke (about 1/3 of the 360,000 incident cases of AD). Therefore, more than 1 million elderly people are currently affected by poststroke VaD in the USA. Since current criteria identify "pure" cases of AD and VaD, it is likely that "AD plus CVD" ("mixed" dementia) could be responsible for a large number of cases currently diagnosed as probable AD. CARDIOGENIC VAD: By 2020, IHD leading to congestive heart failure (CHF) will become the leading cause of disability worldwide. Vascular cognitive impairment occurs in 26% of patients discharged from hospitals after treatment for CHF. Cognitive dysfunction correlates with left ventricular dysfunction and systolic blood pressure below 130 mm Hg. CHF is a leading cause of hospital admissions in Western nations (4.5 million cases in the USA alone) and is a growing problem in developing countries. Furthermore, over 800,000 patients/year undergo coronary artery bypass graft (CABG) surgery worldwide, including 300,000 patients in the USA. Measurable cognitive dysfunction occurs post-CABG in 80-90% of patients at hospital discharge. Long-term (5 years) incidence of cognitive defects is 42%. Finally, an international study found short-term postoperative cognitive dysfunction in 26% of patients (>60 years) after abdominal or orthopedic surgery; most of them may be instances of VaD. In conclusion, VaD may be the most underdiagnosed and undertreated form of dementia in the elderly.

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PubMed2005

Attitudes to dementia and dementia care held by nursing staff in U.K. "non-EMI" care homes: what difference do they make?

BACKGROUND: There is doubt about the value of training in dementia care in U.K. nursing homes. We decided to estimate the association between nursing staff's attitudes to dementia and dementia care and their recognition of cognitive impairment in residents and other indicators of care practice in nonspecialist nursing homes derived from a probability sample of 445 residents in South-East England, and to relate this to previous training. METHODS: Prospective survey. The most senior nurse on duty was interviewed about each resident sampled, about their own training and experience, their attitude to restriction of egress and covert medication use, and asked to complete the Attitudes to Dementia Questionnaire (ADQ) and the dementia Care Styles Questionnaire (CSQ). Nurses were also asked about care practices in relation to restriction of egress and covert medication use in the home. Residents were interviewed using the Mini-mental State Examination (MMSE). RESULTS: One hundred and fifty-eight nurses were interviewed. Increased person-centered attitudes seem to be associated with better recognition of cognitive impairment independent of training and experience. The espousal of restrictive practices was also associated with better recognition, but only when analysis included nurses reporting on only one impaired resident. CONCLUSIONS: More person-centered attitudes are associated with better recognition of cognitive impairment, despite perverse U.K. regulatory incentives; the need for training and support in developing person-centered dementia care for staff in "non-Elderly Mentally Infirm" ("non-EMI") care homes is supported by these results.

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PubMed2000

Frontotemporal dementia with motor neuron disease (amyotrophic lateral sclerosis with dementia).

Frontotemporal dementia (FTD) with motor neuron disease means amyotrophic lateral sclerosis (ALS) with dementia. In the cerebrum of this condition, the medial cortex of the rostral temporal lobe is constantly and most remarkably involved. Another constant and quite characteristic lesion is neuronal loss localized to the CA1-subiculum transitional area at the level of the pes hippocampi. The rostral portion of the parahippocampal gyrus, and the amygdaloid nucleus are also involved. Ubiquitinated intracytoplasmic inclusions are seen in the dentate granule cells and parahippocampal gyrus neurons. Some cases of ALS without dementia show the identical temporal lobe degeneration as well as the cortical ubiquitinated inclusions, thus raising the possibility of overlooked dementia or premature death of the patients. Similarly, recently proposed motor neuron disease-inclusion dementia may be a forme fruste of ALS with dementia.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Prevalence of Alzheimer's disease, vascular dementia and dementia with Lewy bodies in a Japanese population.

We studied the prevalence of dementing disorders in a rural town of Japan (Amino-cho), using a door-to-door two-phase design. Of the 170 persons screened as having cognitive impairment, 142 cases were diagnosed as having dementia. The prevalence (cases/100 aged 65 years older) was 3.8 for all types of dementia, 2.1 for Alzheimer's disease (AD), 1.0 for vascular dementia (VD) and 0.7 for other types of dementia. Among other types of dementia, there were four male patients with dementia with Lewy bodies (prevalence: 0.1), but no patients with frontotemporal lobar degeneration. The overall prevalence was higher in women for AD, while that of VD was the same in both sexes. With results similar to many previous studies in Western countries and some recent surveys in Japan, the present sudy clearly showed that AD is more prevalent than VD.

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PubMed2000

Dementia rating scale performance: a comparison of vascular and Alzheimer's dementia.

Differences in the pattern of neuropsychological dysfunction associated with Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients with AD; (2) patients with single stroke (CVA); and (3) patients with multiple cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on patients that met the DRS criteria for dementia. Dementia groups were similar in age, education, and severity of dementia. Comparisons of the AD and two VaD groups across the specific DRS-scales (Attention, Conceptualization, Construction, Initiation/Perseveration, and Memory) indicated that patients with AD were more impaired on the DRS-Memory while the patients with VaD were more impaired on the DRS-Construction. Additionally, patients with VaD related to MI scored lower on the DRS-Initiation/Perseveration as compared to patients with AD, and patients with AD scored lower on the DRS-Conceptualization as compared to patients with VaD related to CVA. These results are indicative of qualitative differences in the pattern of cognitive deficits associated with the two types of dementia.

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PubMed2004

Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls.

Parkinson's disease is a common neurodegenerative disorder primarily characterized by rigidity, tremor and bradykinesia. Cognitive impairment and neuropsychiatric symptoms are frequent in Parkinson's disease, with a 70% cumulative incidence of dementia. The aim of this cross-sectional study was to establish the pattern of cerebral atrophy on MRI in Parkinson's disease patients with dementia. We used voxel-based morphometry (VBM) to provide an unbiased means of investigating brain volume loss. Whole brain structural T1-weighted MRI scans from Parkinson's disease patients with dementia (PDD, n = 26), Parkinson's disease patients without dementia (n = 31), Alzheimer's disease patients (n = 28), patients with dementia with Lewy bodies (DLB, n = 17) and control subjects (n = 36) were acquired. Images were analysed using SPM99 and the optimized method of VBM. Reduced grey matter volume in PDD patients compared with controls was observed bilaterally in the temporal lobe, including the hippocampus and parahippocampal gyrus, and in the occipital lobe, the right frontal lobe and the left parietal lobe, as well as some subcortical regions. Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects. There was significant grey matter atrophy bilaterally in the occipital lobe of PDD patients compared with Parkinson's disease patients. In addition, significant temporal lobe atrophy, including the hippocampus and parahippocampal gyrus was detected in Alzheimer's disease relative to PDD. No significant volumetric differences were observed in PDD compared with DLB. Thus, Parkinson's disease involves grey matter loss in frontal areas. In PDD, this extends to temporal, occipital and subcortical areas, with occipital atrophy in PDD being the only difference between the two groups. This provides important information about the pattern of cerebral atrophy in Parkinson's disease and PDD.

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PubMed2006

CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia.

As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Abeta) peptides, such as Abeta1-42. Absolute Abeta1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Abeta-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (Abeta-SDS-PAGE/immunoblot) revealed a highly conserved Abeta peptide pattern of the carboxy-terminally truncated Abeta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the Abeta-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Abeta peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Abeta peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and PDD. The Abeta peptide patterns displayed disease-specific variations and the ratio of the differentially altered Abeta1-42 to the Abeta1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Abeta-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized alpha-helical form of Abeta1-40 (Abeta1-40*). The increased abundance of Abeta1-40* probably reflects a disease-specific alteration of the Abeta1-40 metabolism in DLB. We conclude that Abeta peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Abeta peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.

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PubMed1999

Vascular dementia versus dementia of Alzheimer's type: do they have differential effects on caregivers' burden?

OBJECTIVES: We investigated homecare patients with dementia of Alzheimer's type (DAT; n = 36) or vascular dementia (VD; n = 36) and their care-providing relatives regarding clinical and psychosocial variables to determine whether DAT and VD impose different burdens on caregivers. METHOD: All patients were diagnosed according to ICD-10 criteria. The diagnoses were confirmed by internal medical, clinical-neurological, and psychiatric parameters. The severity of the dementias was graded according to the Global Deterioration Scale (GDS). Caregiving relatives responded to the Behavioral Pathology in Alzheimer's Disease Rating Scale (BAD), the Blessed Dementia Scale (BDS), and the Screen for Caregiver Burden (SCB). RESULTS: Analyses revealed that caregivers' burden (SCB), disease symptoms and personality changes of patients (BAD), and the patients' inability to cope with everyday tasks (BDS) were sharply higher for DAT than for VD patients in the group with severe dementia. Concerning patients with mild or moderately severe disease, scores in the DAT group were similar or lower than those in the VD group. CONCLUSION: In early stages, VD patients impose a greater burden on relatives than do patients with DAT. In severe stages this relationship undergoes a reversal, with relatives of DAT patients experiencing the burden more adversely than those of VD patients. The differences in the onset and course characteristics, as well as the specific differences between these two types of dementia with respect to caregiver burden factors, call for their diagnostic separation and the development of specific homecare support systems for family caregivers.

Activities of Daily Living↗
PubMed1992

DSM-III-R criteria for primary degenerative dementia and multi-infarct dementia [corrected].

Primary degenerative dementia (PDD) and multi-infarct dementia (MID) are the two most common categories of cognitive decline in old age. The definitions of these two clinical entities are currently based on clinical evaluation and on the exclusion of other underlying causes, and still lack a consensus. The DSM-III-R criteria are widely used for the diagnosis of dementia. However, their role in the differentiation between PDD and MID has not been thoroughly examined. A consecutive series of 98 demented patients who met the DSM-III-R criteria for dementia were admitted to a clinical study. Upon evaluating their type of dementia according to these criteria, 53 patients could not be diagnosed either as having PDD or MID. The DSM-III-R criteria for these two types of dementia are critically reviewed. Proposed modifications, aimed at refining their differential diagnostic role, are presented, enabling better allocation of demented patients into PDD, MID, or intermediate groups.

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PubMed2004

Posterior cingulate hypoperfusion in Alzheimer's disease, senile dementia of Alzheimer type, and other dementias evaluated by three-dimensional stereotactic surface projections using Tc-99m HMPAO SPECT.

Hypoperfusion in the posterior cingulate cortex is thought to be useful for the early diagnosis of dementia of Alzheimer type (DAT). In the present study, we compared the incidence of posterior cingulate hypoperfusion in patients with Alzheimer's disease (AD), patients with senile dementia of Alzheimer type (SDAT), and patients with other types of dementia, as evaluated by three-dimensional stereotactic surface projection (3D-SSP) imaging. The subjects were 20 AD patients, 20 SDAT patients, 13 frontotemporal dementia patients, and 3 other types of dementia patients. A SPECT study was performed 5 minutes after the injection of 740 MBq technetium-99m hexamethylpropylene amine oxime. 3D-SSP images were obtained with global normalization to perform the statistical analysis. The normal database of 3D-SSP consisted of 15 healthy volunteers. Hypoperfusion was considered to be significant when the Z-score was over 2.5. Posterior cingulate hypoperfusion was observed in 13 of 20 AD patients (65%), in 5 of 20 SDAT patients (25%), but in none of other type of dementia patients. Posterior cingulate hypoperfusion was considered to be a finding specific to DAT, and this finding was thought to be useful to diagnose DAT patients, especially for AD patients. However, it was considered to be difficult to diagnose early-stage SDAT patients.

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PubMed1991

Event-related potentials in senile dementia of Alzheimer's type, multiinfarct dementia and Parkinson's disease.

We investigated event-related potentials (P300) in three types of demented patients. Fourteen patients with senile dementia of Alzheimer's type (SDAT), 15 with multiinfarct dementia (MID), 8 with Parkinson's disease with dementia and 29 normal controls participated in this study. We measured the latencies of N100 and P300 at Pz after odd-ball paradigm stimulation. N100 peaks were within the normal range in all patients. However, P300 peaks were significantly delayed in all demented patients. There were no statistical differences in the mean latencies of P300 in each demented group. P300 latencies were found to be negatively correlated with Hasegawa's dementia scale. These results suggest that regardless of its cause dementia has similar influences on the P300 latency and P300 may be a useful means to assess the degree of dementia.

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PubMed1989

The GBS scale in multi-infarct dementia and senile dementia of Alzheimer type.

The GBS profile was assessed for 39 patients with multi-infarct dementia (MID) and 34 patients with senile dementia of Alzheimer type (SDAT). The MID patients fulfilled the DSM-III criteria for multi-infarct dementia and had a score of 7 points or more on the Hachinski Ischemic Scale (HIS) and a score of 4 points or less on the Gustafson/Nilsson Alzheimer Scale (GNAS). The SDAT patients fulfilled DSM-III criteria for primary degenerative dementia and had a score of 5 points or more on the GNAS and a score of 6 points or less on the HIS. The total GBS score, the GBS subscale and relative subscale scores for intellectual functioning were significantly higher in patients with SDAT as compared with patients with MID. However, these subscale scores were considerably dispersed and nearly totally overlapping between patients with MID and SDAT, which implicates that the discriminative value is minimal. The validity between the GBS versus HIS and between the GBS versus GNAS was divergent, suggesting that the GBS scale has its own unique validity. In conclusion, the study does not support the hypothesis that the GBS profile may be of diagnostic value in clinical differentiation between multi-infarct dementia (MID) and senile dementia of Alzheimer type (SDAT).

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PubMed1975

Analysis of intellectual and cognitive performance in patients with multi-infarct dementia, vertebrobasilar insufficiency with dementia, and Alzheimer's disease.

A prominent feature in dementia is intellectual deterioration. Review of the clinical literature indicates a lack of suitably quantitated studies of specific intellectual defects in dementia. The present study investigated the performance of patients with multi-infarct dementia (MID), dementia due to Alzheimer's disease (AD), and vertebrobasilar insufficiency (VBI) with dementia using the Wechsler Adult Intelligence Scale (WAIS). Forty-two patients ranging in age from 45 to 85 years (x 66) were included. Significant differences in cognitive and intellectual performance were found between patients with dementia due to VBI and MID versus neuronal atrophy of the Alzheimer's type. The group with AD performed significantly and consistently lower on all measures. There were no significant differences between the two cerebrovascular disease groups, even though the MID group performed consistently more poorly than the VBI group. A discriminant function analysis classified 74% of the patients correctly based on the individual WAIS scores. The diagnosis was more easily made when tasks measuring visual motor coordination and abstract reasoning were included in the analysis.

Age Factors↗
PubMedDate not supplied

Clinical aspects of 'senile dementia of the tangle type'-- a subset of dementia in the senium separable from late-onset Alzheimer's disease.

There is a subset of dementia patients in the senium, in whom abundant neurofibrillary tangles (NFTs) are present mainly in the hippocampal region without significant numbers of senile plaques. This patient group was thought to be separable from those with Alzheimer's disease based on the results of ApoE allele analysis in addition to the substantial absence of amyloid beta deposits and has been designated as senile dementia of the tangle type (SDT). The clinical pictures of 4 autopsied patients with different amounts of NFTs were examined to characterize the clinical aspects of this type of senile dementia. SDT generally occurs in very old patients and was estimated to account for about 4-6% of patients with dementia in the senium excluding vascular dementia. Clinically, long-lasting memory disturbance is more prominent and personality as well as cognitive functions tend to be preserved. Delirium and other psychotic symptoms are often observed. NFTs and accompanying neuronal loss in the limbic, mainly in the hippocampal, region could be responsible for dementia.

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PubMed2005

Prevalence, resource utilization and costs of vascular dementia compared to Alzheimer's dementia in a population setting.

OBJECTIVES: To determine the prevalence of dementia and to measure the monetary impact and health resources utilization of vascular dementia (VD) compared to Alzheimer's dementia (AD) in persons aged over 64 years in a population setting. METHODS: Retrospective, cross-sectional study. In the initial phase, information was obtained on specific clinical characteristics from the subjects with an active diagnosis of dementia. The second phase consisted of a clinical evaluation and validation of the cases. Mini-Mental State Examination was used to assess cognitive impairment. Dementia and its subtypes were determined using established diagnostic criteria. Information was obtained on the use of health care resources (direct costs) and the number of hours devoted by the primary caregiver (indirect costs) for patients with a documented diagnosis of AD or VD within the last 6 months prior to the interview. A multiple logistic regression analysis was performed to correct the model. RESULTS: A total of 6,004 subjects were analyzed, 258 with diagnosis of dementia (overall prevalence: 4.3%). An evaluation was made of 224 patients, and gross prevalence of AD and VD was 2.4 and 1.0%, respectively. Cost per patient per semester was EUR 8,086 for AD and EUR 11,039 for VD (p = 0.016). 85.5% of the cost was attributable to primary caregiver time in AD and 84.4% in VD. CONCLUSIONS: The prevalence of AD and VD increases with age. No sociodemographic differences were seen between AD and VD. Costs associated with health care resource and primary caregiver utilization were high, being higher in VD than in AD.

Age Distribution↗
PubMed2005

Early-onset dementia: frequency and causes compared to late-onset dementia.

BACKGROUND: Research on the epidemiology of dementia has focused on the elderly. Few investigations have studied differences in etiologic frequencies between early-onset dementia (EOD), with onset at an age of less than 65 years old, and the more common late-onset disorder. OBJECTIVES: To determine relative frequencies and characteristics of EOD versus late-onset dementia (LOD; age of onset > or =65 years) diagnosed in a large memory disorders program over a 4-year period. METHODS: We reviewed medical records, including an extensive neurobehavioral and neurological evaluation, of all patients seen at a large Veteran's Affairs Medical Center Memory Disorders clinic between 2001 and 2004 and assessed demographic variables, final diagnoses, presence of dementia, and differential diagnosis of dementing illnesses. RESULTS: Among 1,683 patients presenting for evaluation of an acquired decline in memory or cognition, 948 (56%) met established clinical criteria for a dementing illness. About 30% (n = 278) of these had an age of onset of <65 years, compared to 670 with LOD. Patients were predominantly male (98%). Compared to the late-onset group, the EOD patients were less severely impaired on presentation, but they did not differ in gender distribution or educational background. The EOD group had significantly more dementia attributed to traumatic brain injury, alcohol, human immunodeficiency virus (HIV), and frontotemporal lobar degeneration compared to the LOD patients. In contrast, the LOD group had significantly more Alzheimer's disease compared to the EOD group. CONCLUSIONS: This study, conducted at a Veterans Affairs Hospital, is the largest series to date on EOD, and found a previously unexpectedly large number of patients below the age of 65 with cognitive deficits and impaired functioning consequent to head trauma, alcohol abuse, and HIV. These findings highlight the differential distribution and importance of preventable causes of dementia in the young.

Age of Onset↗
PubMed1990

Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia.

From a series of 460 dementia patients referred to a regional brain bank, 14 (3%) patients had a pathologic diagnosis of primary degeneration of the brain involving multiple sites (frontoparietal cortex, striatum, medial thalamus, substantia nigra, and hypoglossal nucleus), with cell loss and astrocytosis. There were no neuronal inclusions and essentially no senile plaques. This entity, which we have termed "dementia lacking distinctive histology" (DLDH), presented with memory loss and personality changes, and led to death, usually within 2 to 7 years. Dysarthria and dysphagia were prominent in the later phases of the illness in most patients. The psychometric findings of some of the patients were consistent with a "frontal" lobe dementia. A few patients had prominent caudate atrophy on CT as well as neuropathologically. Eight of our patients had positive family histories for neurologic disease, mainly dementia. DLDH, in addition to Pick's disease, is a major member of the frontal-lobe dementia group. In patients under age 70 years, the frontal lobe dementias represent an important diagnostic consideration.

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