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Apolipoprotein E (APOE) allele frequencies in late-onset sporadic Alzheimer's disease (AD), mixed dementia and vascular dementia: lack of association of epsilon 4 allele with AD in Italian octogenarian patients.

The Apolipoprotein E (APOE) epsilon 4 allele has been found to be strongly associated with Alzheimer's disease (AD) in most studies conducted up to now, though not all investigators have established a similar association with other forms of dementia, like vascular dementia. Our study examined the APOE polymorphism in a sample of 149 dementia patients, of which there were 80 with probable sporadic late-onset AD, 16 with a mixed form of dementia (MD), and 53 with vascular dementia (VD). An elderly control sample was composed of 126 subjects. The data obtained on the whole AD sample did not confirm the association already reported with APOE epsilon 4. A difference did emerge when the subjects were subdivided on the basis of age at the examination. AD patients aged < or = 80 years significantly differed from the correspondent elderly controls, while no difference was observed between the patients aged 81 years or older and controls. This pattern could be due to a previous disadvantageous effect of the epsilon 4 allele on the subjects bearing it. A substantially similar pattern was observed in the few MD patients, while no differences were found in the two VD subgroups. The odds ratio (OR) for AD associated with at least one epsilon 4 allele was significant and equal to 3.3 (95% CI = 1.2-9.1) for the < or = 80 age class, while it was not significant and equal to 1.1 (95% CI = 0.4-2.8) for the > 80 age class. Our data indicate that in AD patients aged less than 81 years, epsilon 4 is clearly associated with AD and that it can be considered a risk factor for AD chiefly before this age.

Age of Onset↗

[Neuropsychological pattern of cognitive impairment in Alzheimer type dementia and vascular dementia].

BACKGROUND: Cummings et al, 1987, hypothesized that Alzheimer dementia type (ADT) patients would present poorer performances than vascular dementia (VD) patients on the neuropsychological tests that mainly involve cortical neurological structures, and that VD would perform worse on tests that mainly involve subcortical structures. The main purpose of the research was to identify a cognitive impairment pattern that discriminates the type of dementia in the initial stages. METHOD: Two groups of patients, one affected by mild ADT (n = 30) and the other by multi-infarct dementia (VD, n = 30) were given a neuropsychological battery. The battery was composed by Temporal Orientation (Benton et al.); Vocabulary, Similarities, Digits, Coding and Kohs (WAIS) of Wechsler; the Colour-Form Test of Weigh; the Trail Making Test (A and B) (Halstead-Reitan Neuropsychological Battery); Tapping (McQuarrie); Logical Memory, Visual Memory and Paired Association (Wechsler Memory Scale) of Wechsler; Delayed Memory (Russell). The two groups were similar in age and socio-cultural features. The z-score and its statistical significance on the Mann-Whitney test were made and we performed an exploratory discriminant analysis to the classification. RESULTS: In general, results were poorer in the ADT group. But we detected no significant differences in the tests, although some test (Immediate Visual Memory and Kohs' Blocks) almost reached significance. The discriminant analysis reached a classification of the 67% of the subjects into the ADT group and the 70% of the subjects into the VD group. CONCLUSIONS: In the initial stages of dementia it is difficult to differentiate between a cortical pattern of cognitive impairment in ADT and a subcortical pattern in VD, a distinction that the other researchers have reported. When complex tests were used the performance depended on the coordination of multiple related systems. These findings are in agreement with the holistic models of higher mental functions.

Aged↗

Is senile dementia "age-related" or "ageing-related"?--evidence from meta-analysis of dementia prevalence in the oldest old.

The observation of an exponential increase in senile dementia prevalence with age has led to the conclusion that this disease may be inevitable in those who live long enough. The alternative view is that at very high ages the prevalence rate levels off. Studies conducted to date have not included sufficient numbers of very old people to resolve this difference of opinion. The question is important both to our understanding of the biological mechanisms involved and for public health planning. We have carried out a meta-analysis of nine epidemiological studies of senile dementia that used DSM III diagnostic criteria and that included samples of elderly people over age 80. The resulting curve was best described as a flattened S curve that fitted a modified logistic function rather than an exponential pattern. The rate of increase in senile dementia prevalence was found to fall in the age range 80-84, and at around the age of 95 prevalence was seen to level off to about 40%. It seems that senile dementia is better conceptualised as an "age-related" (ie, occurring within a specific age range) rather than as an "ageing-related" disorder (that is, caused by the ageing process itself). Very elderly survivors may be at diminishing risk of dementia and this has implications for public health policy.

Age Factors↗

An open-label extension trial of galantamine in patients with probable vascular dementia and mixed dementia.

BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are the most common types of dementia worldwide. Galantamine, an acetylcholinesterase inhibitor and allosteric nicotinic modulator, has shown broad clinical benefits in patients with mild to moderate dementia due to AD, probable VaD, or AD with cerebrovascular disease (CVD)-so-called mixed dementia. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety profiles of galantamine 24 mg/d in patients with VaD or AD with CVD over the longer term (>6 months). METHODS: This was an open-label extension of a 6-month double-blind study of galantamine. Patients who had been randomized to receive galantamine 24 mg/d or placebo in the double-blind phase were eligible to continue open-label treatment with galantamine 24 mg/d for 6 months. The primary efficacy end point was change in cognition, based on scores on the 11-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog/11). Secondary measures included changes in functional ability (as measured on the Disability Assessment for Dementia [DAD]) and behavior (as measured on the Neuropsychiatric Inventory [NPI]). Safety and tolerability were also monitored. RESULTS: Four hundred fifty-nine patients (240 men, 219 women; mean [SE] age, 75.2 [0.33] years) entered the open-label phase. Of these patients, 195 (42.5%) had a diagnosis of probable VaD, and 238 (51.9%) had a diagnosis of AD with CVD; the remainder had an inconclusive diagnosis. At month 12 of the study, improvements from baseline (the start of the double-blind phase) in ADAS-cog/11 scores were observed in both the group that received placebo during the double-blind phase (placebo/galantamine group: -0.3 point; 95% CI, -1.64 to 1.06) and the group that received galantamine during the double-blind phase (galantamine/galantamine group: -0.9 point; 95% CI, -1.73 to 0.03). Improvement in functional ability was demonstrated by statistically significant mean (SE) changes from baseline in DAD score in both the placebo/galantamine group (-7.4 [1.68]; P < or = 0.001) and the galantamine/galantamine group (-3.6 [1.33]; P < or = 0.01). There was no significant change in mean (SE) NPI scores in either group (0.2 [0.98] and 0.1 [0.70], respectively). Galantamine treatment was well tolerated. CONCLUSIONS: In these patients with VaD and AD with CVD, galantamine treatment produced similar sustained benefits in terms of maintenance of or improvement in cognition (ADAS-cog/11), functional ability (DAD), and behavior (NPI) after 12 months.

Aged↗

Conceptualization and measurement of quality of life in dementia: the dementia quality of life instrument (DQoL).

Direct assessment of quality of life (QoL) of persons with dementia has largely been ignored due to logistical, conceptual and practical issues. This article presents a disease-specific conceptual framework of QoL for dementia. Based on this conceptualization, a 29-item instrument designed to assess QoL by direct interview with dementia patients was developed and tested on 99 participants. The data show that the instrument is reliable and shows evidence of validity. Nearly all participants (96%) were able to respond to questions appropriately. Thus, persons with mild to moderate dementia can be considered good informants of their own subjective states, paving the way to consider patient responses rather than proxy measures as the gold standard for assessing QoL for persons with dementia.

Aged↗

The Comprehensive Psychopathological Rating Scale in patients with dementia of Alzheimer type and multiinfarct dementia.

Eighteen patients with the clinical diagnosis dementia of Alzheimer type (AD/SDAT) and 20 patients with the clinical diagnosis multiinfarct dementia (MID) were interviewed using a subscale to the Comprehensive Psychopathological Rating Scale (CPRS), consisting of items measuring psychopathological symptoms and signs commonly seen in patients with dementia. The aim of the investigation was to evaluate whether a difference in psychopathology between AD/SDAT and MID could be observed during a semistructured psychiatric interview using the CPRS. In both groups the duration of illness was similar and the dementia mild to moderate. All patients were subjected to somatic, psychiatric, laboratory, neurophysiologic and neuroradiologic examinations in order to obtain the correct clinical diagnoses. The results show that patients with AD/SDAT have a more variable psychopathology than patients with MID. Patients with MID were rated lower on all items used, especially those concerning verbal and personal contact. This might explain the generally accepted opinion that patients with MID have better contact with their surroundings and better preservation of their personality, even though they have the same degree of dementia as patients with AD/SDAT.

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Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies.

BACKGROUND: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson's disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson's disease (PD). AIMS: (1) To examine rates of cognitive and motor decline over two years in PD (n=40), PDD (n=42) and DLB (n=41) subjects, compared with age matched controls (n=41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. RESULTS: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE -4.5 and -3.9, respectively), compared with PD (-0.2) and controls (-0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (chi2=6.7, Fisher's exact test p<0.05). CONCLUSION: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.

Aged↗

Coagulation and fibrinolysis markers and risk of dementia. The Dutch Vascular Factors in Dementia Study.

We performed a cross-sectional case-control study among 277 subjects with dementia and 298 control subjects drawn from participants of the Rotterdam Study, a population-based cohort study among subjects aged 55 years or over, and from participants of the Rotterdam Stroke Databank, a hospital-based stroke registry, with the objective to evaluate the association of indicators of coagulability, fibrinogen, prothrombin fragments 1+2, thrombin-antithrombin complex (TAT), and indicators of fibrinolysis, plasmin-inhibitor complex, D-dimer and tissue-type plasminogen activator (t-PA) with dementia. Increased levels of TAT, D-dimer and t-PA activity were associated with an increased risk of dementia. Additional stratified analyses indicated that an increased TAT level was the primary factor related to dementia. The present study provides evidence that predominantly increased thrombin generation is associated with dementia.

Aged↗

CT and MRI findings among African-Americans with Alzheimer's disease, vascular dementia, and stroke without dementia.

We compared CT and MRI findings among 78 Alzheimer's disease (AD), 66 vascular dementia (VaD), and 41 stroke without dementia (SWD) African-American patients to identify possible neuroimaging indicators of dementia. The patients with AD and VaD were generally older and less educated than those with SWD. VaD and SWD patients had a higher frequency of cardiovascular disease risk factors than those with AD. In multivariate analysis, the CT data showed that the presence of white matter lesions, nonlacunar infarcts, and left subcortical infarcts were predictors of VaD when compared with AD, whereas atrophy of the third ventricle and equal distribution of white matter lesions distinguished VaD from SWD. On MRI, atrophy of the temporal sulci, temporal horns, and the third ventricle, and right hemisphere infarcts, distinguished AD from VaD, while atrophy of the third ventricle differentiated VaD from SWD. These data suggest that atrophy, especially at the level of the third ventricle, presence of infarcts, and white matter lesions may be useful predictors of dementia subtype. Furthermore, the qualitative CT and MRI findings among our African-American patients were similar to those reported in other dementia studies.

Black or African American↗

Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia.

The authors determined rates of brain atrophy, as assessed by the boundary shift integral on serial MRI, in patients with dementia with Lewy Bodies (DLB, n = 10), AD (n = 9), vascular dementia (VaD, n = 9), and age-matched controls (n = 20). Mean % +/- SD atrophy rates per year were as follows: DLB, 1.4 +/- 1.1; AD, 2.0 +/- 0.9; VaD, 1.9 +/- 1.1; and controls, 0.5 +/- 0.7. Dementia subjects had higher rates than controls (p < 0.001), but there were no significant differences between the three dementia groups. The authors found accelerating atrophy with increasing severity of cognitive impairment, further emphasizing the need for early diagnosis and intervention in dementia.

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[The study of dementia patients who showed intellectual improvement after admission to a hospital where they could be given special therapy for dementia].

The authors evaluated the changes in the scores on Hasegawa's rating scale for dementia (HRSD) of demented patients in a hospital for dementia. The subjects in this study were 69 patients (12 males and 57 females) including 34 with dementia of the Alzheimer type (DAT), 30 with multi-infarct dementia (MID) and 5 with mixed dementia. Their average age was 75.6 years and the mean period after symptom onset was 2.5 years. The observation period was 5 months after admission to the hospital. We rated HRSD on admission and each month after admission. During the observation period, 65 patients received drugs orally and 65 patients were given rehabilitation for impaired cerebral function. We tried to classify the pattern of change in the HRSD into 5 groups as follows; 1) no remarkable change or deterioration, 2) wavering, 3) improvement during only the first month, 4) improvement from the first month after admission, 5) improvement from admission. We assumed that the patients in group 3) had been underestimated on admission. Their mental states might have been confused on admission because of the change in their living environment. Thus we rejected this group for statistical analysis and compared the medical characteristics of those in the non-improved group (1 and 2) with those in the improved group (4 and 5). The period from onset of symptoms in the improved group was shorter than in the non-improved group (p less than 0.05). Moreover there was a tendency (p less than 0.1) toward less abnormal findings in the EEG and less cerebral atrophy on CT scan in the improved group.(ABSTRACT TRUNCATED AT 250 WORDS)

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Differentiation of dementia with Lewy bodies, Alzheimer's disease and vascular dementia by cardiac 131I-meta-iodobenzylguanidine (MIBG) uptake (preliminary report).

OBJECTIVE: Differentiation of dementia with Lewy bodies (DLB), vascular dementia (VAD), and Alzheimer's disease (AD) is difficult in clinical practice. Several new techniques have been used for differentiation of various types of dementia. Among these techniques 123I-meta-iodobenzylguanidine (MIBG) uptake was reported to have benefit in distinguishing DLB from AD. The authors study the role of MIBG as a tool for differentiation of DLB, AD and VAD. METHOD: Patients with dementia were recruited to the study by DSMIIIR criteria. Diagnosis of each dementia type was made by standard clinical criteria. Brain imagings and 131I-MIBG uptake were performed in all the studied patients. RESULTS: Five DLB, 3 AD and 3 VAD patients were clinically diagnosed. The heart/mediastinum (H/M) ratio in 4 out of 5 in DLB was significantly lower than H/M ratio in patients with AD and VAD. AD patients had the highest uptake of MIBG MIBG uptake of VAD patients was in the range between AD and DLB but the values were close to the AD group. CONCLUSIONS: 131I-MIBG is helpful in differentiating DLB from AD.

3-Iodobenzylguanidine↗

[Computer tomography contribution to the differential diagnosis of dementia of vascular origin (multi-infarction type) and primary degenerative dementia (Alzheimer type)].

Studies of computed tomography were performed in 367 patients diagnosed as dementia clinically. The mean age was 70.1 years. By the clinicians 240 were classified as senile dementia of Alzheimer's type, 79 as multiinfarct dementia, and 48 were not determined definitely. In 3%, the CT studies did detect treatable causes like tumors, subdural hematomas and communicating hydrocephalus. In about 57% was found by CT a diffuse brain atrophy without focal tissue changes as to expect if occurring a cerebrovascular disease. In 25% there were focal changes of the brain tissue in CT to define as residuals of infarctions in addition to the signs of cerebral atrophy. The results of the CT studies were normal in 15% despite of the evidence of dementia clinically. The analysis of the material did show that a cerebrovascular disease as a cause of dementia is suspected clinically in much more cases than CT studies are able to prove focal pathological changes of the brain tissue due to disorders of cerebral blood flow really.

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[Multicenter register of index cases of dementia. A study by the Spanish Neurological Society's dementia group].

We report the objectives and case registration methods used by neurologists belonging to the Spanish Neurological Society's dementia group (GERMICIDE). Forerunners of the present project are also described. The group's principal aim, which is to determine the distribution of dementia in the "neurological" environment is pursued by enrolling consecutive index cases (new presentations) arriving at 18 Spanish neurological units over a period of 2 years. A standard protocol was used to study the patients and final diagnoses were agreed upon in keeping with international criteria for dementia and the main neurological diseases (DSM-III-R, CDR and others). A second objective is to study risk factors for the main etiological groups of dementia (Alzheimer's disease and vascular dementia) and to follow each patient in the cohort until death in order to assess the course of disease and its biological markers. The series will be large, as there are already over 800 cases listed in the coordinating centre even though the period of enrollment has not ended.

Adult↗

[Presenile dementia with marked recent memory disturbance--in relation to hippocampal dementia].

Two cases of presenile dementia with marked recent memory disturbance were reported. Patient 1 is a 54-year-old woman. She noticed forgetfulness at the age of 51 years. Neurological examination at aged 52 revealed marked recent memory disturbance, but examination by WAIS (Wechsler Adult Intelligence Scale) showed good results (verbal IQ 106, performance IQ 104, total IQ 106). There was neither disorientation in place nor character change. Cranial CT scan and MRI revealed the absence of brain atrophy. About 3 years after the onset of the disease, the degree of dementia is slight and disorientation in place does not appear. Patient 2 is a 67-year-old man. He noticed forgetfulness at the age of 63 years. Neurological examination at aged 66 revealed marked recent memory disturbance, but examination by WAIS-R showed moderate results (verbal IQ 89, performance IQ 87, total IQ 88). There was neither disorientation in place nor character change. Cranial CT scan and MRI revealed slight dilatation of the inferior horns of the lateral ventricle and slight cortical atrophy. About 4 years after the onset of the disease, the degree of dementia was slight and disorientation in place did not appear. We can not rule out the possibility that our cases belong to Alzheimer's disease, but the clinical course of our cases is peculiar. In the relation of responsible lesion in pure amnestic syndrome, hippocampal dementia, and simple senile dementia, our cases are interesting and important.

Aged↗

Costs of dementia and dementia care: a review.

Costs of dementia care constitute a great part of the total costs of care for elderly. Because the prevalence of dementia is linked to increasing age, and the number of the oldest old is rising, the costs of dementia care will increase considerably in the forthcoming decades. In this review, research describing costs of dementia care has been analysed and classified. The available database in this field is small, though expanding, and the methodological problems are obvious. Differences between countries, and between different periods of time, are difficult to analyse due to different methods of financing and organizing care. The main result of the present study is that the costs of dementia care differ considerably in the literature. One important reason for this variability is that the number of included cost categories vary, leading to a wide range of costs. Unpaid informal care forms a major part of the total costs, but the theory of costing informal care is complicated.

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A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson's disease with and without dementia.

OBJECTIVES: To compare the frequency and clinical correlates of neuropsychiatric symptoms in patients with Parkinson's disease (PD) with and without dementia and in those with dementia with Lewy bodies (DLB). METHODS: Neuropsychiatric symptoms during the month prior to assessment were assessed in clinically diagnosed PD patients with dementia (PDD; n = 48) and without dementia (PDND; n = 83) and in 98 DLB patients (33% autopsy confirmed) using standardized instruments. RESULTS: Delusions and hallucinations were significantly more common in DLB (57% and 76%) than PDD (29% and 54%) and PDND (7% and 14%) patients (p < 0.001). In all groups, auditory and visual hallucinations and paranoid and phantom boarder delusions were the most common psychotic symptoms. Frequency of major depression and less than major depression did not differ significantly between the three groups. Clinical correlates of hallucinations in PD were dementia (odds ratio (OR) = 3.9; 95% confidence interval (CI) 1.5-10.4) and Hoehn-Yahr stage 3 or more (OR 3.4; 95% CI 1.0-12.0), whereas no significant clinical correlates of hallucinations were found in DLB patients. CONCLUSIONS: Delusions and hallucinations occur with increasing frequency in PDND, PDD and DLB patients, but the presentation of these symptoms is similar. These findings support the hypothesis that psychiatric symptoms are associated with cortical Lewy bodies or cholinergic deficits in the two disorders.

Aged↗

Cognitive conditions of pathologically confirmed dementia with Lewy bodies and Parkinson's disease with dementia.

The relationship between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) has been insufficiently described, and it is still problematic. Twenty-nine cases of DLB and 10 cases of PDD were investigated in the present study. DLB cases disclosed a significantly older disease onset and shorter disease duration than PDD cases (p<0.01 each). However, they showed no significant difference in dementia onset or dementia duration (p>0.05 each). Motor symptoms (parkinsonism) were suspected as the cause of the younger disease onset in PDD cases. Compared with 10 age-matched cases of definite Alzheimer's disease, both 19 DLB cases and 6 PDD cases had significantly better scores in the final test of mini-mental state examination (MMSE) and revised version of Hasegawa's Dementia Scale (HDSR) within 12 months before death, although no significant differences between DLB and PDD were indicated. DLB and PDD were suspected to show cognitive impairment of similar severity in the terminal stage. They would thus be difficult to classify as completely different entities.

Age of Onset↗