Behavioural and psychological symptoms of Alzheimer type dementia are not correlated with plasma homocysteine concentration

BACKGROUND/AIMS: Vitamin B12 and folate deficiencies have been associated with cognitive impairment and various psychiatric symptoms but not specifically with behavioural and psychological symptoms of dementia (BPSD). A limitation of previous studies in dementia was lack of concurrent homocysteine measurement especially as it may provide a better indicator of tissue activities of these vitamins. This study was designed to clarify whether a relationship exists between plasma homocysteine concentration and BPSD. METHODS: Plasma homocysteine, serum vitamin B12 and folate were measured in 23 Alzheimer's disease (AD) patients with BPSD and 27 AD patients without BPSD as determined through the use of the Neuropsychiatric Inventory (NPI). Blood levels of measured substances were also correlated with individual NPI scores and with cumulative NPI scores for different cluster of symptoms. RESULTS: There was no significant difference (p = 0.956) in the mean plasma homocysteine levels between AD patients with BPSD (17.48 micromol/l) and AD patients without BPSD (17.34 micromol/l). Similarly, there was no significant difference between the two groups in the mean serum B12 (382.61 and 391.60 pg/ml, respectively) and folate (7.95 and 10.02 ng/ml, respectively). Mean levels for both vitamins were well within the laboratory reference range. Neither individual nor cluster NPI scores correlated significantly with plasma homocysteine. CONCLUSION: This study shows for the first time that BPSD are not associated with hyperhomocysteinaemia in Alzheimer dementia. Although previous studies have identified homocysteine as an independent risk factor in AD, the results reported here do not lend weight to an aetiological role for homocysteine specifically in BPSD.     

Subnormal serum vitamin B12 and behavioural and psychological symptoms in Alzheimer's disease

The objective of this study was to examine whether patients with Alzheimer's disease (AD) with subnormal vitamin B12 levels show more frequent behavioural and psychological symptoms of dementia (BPSD) than AD patients with normal vitamin B12 levels. The design was a prospective case-control study. The study took place at a memory-clinic of a department of geriatric medicine in a teaching hospital. There were seventy-three consecutive outpatients with probable AD, including 61 patients with normal and 12 patients with subnormal (<200 pg/ml) vitamin B12. BPSD were measured using the subscales disturbed behaviour and mood of the Nurses' Observation Scale for Geriatric Patients (NOSGER), the Cornell Scale for Depression and the four criteria for personality change in dementia from the International Classification of Diseases (ICD-10). Controlling for dementia duration and degree of severity of the cognitive deficits, there were significant inverse associations between vitamin B12 status and ICD-10 irritability (p=0.045) and NOSGER subscale disturbed behaviour (p=0.015). Low vitamin B12 serum levels are associated with BPSD in AD. Vitamin B12 could play a role in the pathogenesis of behavioural changes in AD.     

Neuropsychiatric symptoms of dementia: cross-sectional analysis from a prospective, longitudinal Belgian study

OBJECTIVE: Given the rather limited knowledge on profiles of neuropsychiatric symptoms (behavioural and psychological signs and symptoms of dementia, BPSD) in several degenerative dementias, we designed a prospective study of which we here present the baseline data. METHODS: Diagnosed according to strictly applied clinical diagnostic criteria, patients with probable Alzheimer's disease (AD) (n = 205), frontotemporal dementia (FTD) (n = 29), mixed dementia (MXD) (n = 39) and dementia with Lewy bodies (DLB) (n = 23) were included. All patients underwent a neuropsychological examination and behavioural assessment by means of a battery of scales (Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia). RESULTS: In AD and MXD, activity disturbances and aggressiveness occurred in more than 80% of the patients. With a prevalence of 70%, apathy was very common whereas delusions and hallucinations were rare in FTD patients. Frequently used behavioural assessment scales like the Behave-AD systematically underestimated BPSD in FTD whereas the MFS displayed high sensitivity for frontal lobe symptoms. Hallucinations discriminated DLB patients from other dementias. A high prevalence of disinhibition (65%) in DLB pointed to frontal lobe involvement. CONCLUSIONS: Behavioural assessment may help differentiating between different forms of dementia, further stressing the need for the development of new and more sensitive behavioural assessment scales. By means of the MFS, frontal lobe involvement was frequently observed in DLB. As 70% of FTD patients displayed apathy, prevalence was about two times higher compared to the other disease groups, meanwhile indicating that apathy is frequently observed in dementia, irrespective of its etiology.     

Effects of aging on behavioral symptoms in Alzheimer's disease

Aim:  The aim of the present study was to evaluate the relationship between aging and the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD).
Methods:  Eligible subjects were consecutively referred AD patients with BPSD. According to patient age at the time of the test, the AD patient group ( n  = 79, whole AD group (WADG)) was divided into two groups: a relative older group (OG) in the whole AD group (WAD) (age at the time of test was 81 years or more, n  = 40) and a relative younger group (YG) in the WAD (age at the time of test was below 81 years, n  = 39). A comparison was made of the demographic data (sex difference, educational level and severity of dementia), cognitive functions and BPSD between the groups. BPSD was evaluated using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). The factor analysis of BPSD was conducted in the WADG as well as in the OG and YG.
Results:  Sex difference, educational level, severity of dementia and cognitive functions were not different; however, the total score of the BEHAVE-AD symptom domain in diurnal rhythm was significantly higher in the OG than in the YG (Student's t -test: P  < 0.05). Factor analysis showed that psychosis was the first factor in the OG, but was the third factor in the YG and that the psychotic symptoms were caused by anxieties and phobias in the OG.
Conclusion:  From these results, we found that the effects of aging on the BPSD in AD were characterized by diurnal rhythm disturbance and psychosis.     

Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study

There is some debate regarding the differing levels of plasma homocysteine, vitamin B12 and serum folate between healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112 participants (768 HC, 133 MCI patients, and 211 AD patients), plasma homocysteine, vitamin B12, and serum and red cell folate were measured at baseline to investigate their levels, their inter-associations, and their relationships with cognition. The results of this cross-sectional study showed that homocysteine levels were increased in female AD patients compared to female HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not serum folate, was decreased in AD patients compared to HC (-10%, p-value = 0.004). Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with homocysteine, in all clinical categories. Increasing red cell folate had a U-shaped association with homocysteine, so that high red cell folate levels were associated with worse long-term episodic memory, total episodic memory, and global cognition. These findings underscore the association of plasma homocysteine with cognitive deterioration, although not unique to AD, and identified an unexpected abnormality of red cell folate.     

Folate, vitamin B12 and cognitive impairment in patients with Alzheimer's disease.

This study examines the relationship between folate, vitamin B12 and severity of cognitive impairment in patients with Alzheimer's disease (AD) as compared with other disorders associated with cognitive impairment. The patients were 97 consecutive referrals to an AD clinic. Forty patients had either possible or probable AD, 31 had other dementias (OD) and 26 had mild cognitive impairment (cognitively impaired, not demented; CIND). Patients had blood drawn for serum, red cell folate and B12, as well as other biochemical indicators of nutrition, within 24 h of the Mini-Mental State Examination (MMSE). In the AD group, only B12 was significantly correlated with MMSE. Using regression analysis, B12 contributed significantly to variance in MMSE. There was no correlation between MMSE and serum, red cell folate or B12 in the OD or CIND group and no significant correlation between MMSE and other nutritional indices in any group. These findings suggest the possibility of a specific relationship between B12 levels and severity of cognitive impairment in patients with AD.     

Alzheimer's disease and frontal variant of frontotemporal dementia

The aim of this study was to investigate whether a brief neuropsychological battery consisting of a limited number of cognitive tests and an evaluation of the behavioural domains intended to discriminate between frontotemporal dementia (fv–FTD) and Alzheimer's disease (AD), constitutes a useful instrument for making a differential clinical diagnosis between these two pathologies. Nineteen fv–FTD and 39 AD patients were compared on cognitive tasks (assessing memory, executive functions, language and constructional praxis) and on the NPI behavioural assessment. A stepwise discriminant analysis was performed to identify the linear combination of cognitive and behavioural measures able to best discriminate between the two groups. One test for each of the investigated cognitive domains (Delayed Prose Recall, FAS verbal fluency, Boston naming test, Rey's Figure A Copy) and the four subscales of the Neuropsychiatry Inventory (NPI) which best differentiated between fv–FTD and AD patients (apathy, disinhibition, euphoria, aberrant motor behaviour) were used. The analysis selected Rey's Figure A Copy, FAS verbal fluency and NPI apathy subscale as the best discriminants between fv–FTD and AD patients. The final equation assigned 73.7% of the fv–FTD patients and 94.7% of the AD patients to the correct diagnostic group. A validation study conducted on a new independent sample of 11 fv–FTD and 22 AD patients confirmed the high sensitivity (82.6 %) and specificity (81.8%) of the diagnostic equation in assigning fv–FTD and AD patients to the correct dementia group. Although both cognitive and behavioural differences exist between FTD and AD, previous studies have aimed at differentiating the two pathologies by considering the two aspects separately and discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. The present results emphasise the importance of rating both cognitive and behavioural clinical features of the two syndromes as objectively as possible to improve differential diagnostic accuracy.     

Role of vitamin B12, folate, and thyroid stimulating hormone in dementia: A hospital-based study in north Indian population

Background:

Vitamin B₁₂ and folate represent modifiable risk factors for dementia. They may increase the risk of Alzheimer′s dementia (AD) and vascular dementia (VaD) as their deficiency can increase the homocysteine level due to slowed methylation reaction. Homocysteine has a neurotoxic effect that could lead to neurologic disturbances. Hence, it is important to explore the status of serum B₁₂ and folate in AD and VaD to evolve the treatment strategies for the same.

Objectives:

A retrospective study was conducted to assess the levels of vitamin B₁₂, folate, and thyroid stimulating hormone (TSH) in serum and the relationship of these factors, including age and sex to cognitive decline in VaD, AD, and dementia due to other causes (DOC).

Materials and Methods:

Serum vitamin B₁₂, folate, TSH, and total cholesterol were studied in 32 AD patients (mean age: 65 years), 12 VaD patients (mean age: 61 years), 83 DOC (mean age: 65 years), and 127 control subjects (mean age: 49 years). Results: In AD, VaD, and DOC, the levels of vitamin B₁₂ and folate were significantly lower (P < 0.002; 0.026; 0.002 for vitamin B₁₂ and P < 0.000 in all the 3 groups for folate) as compared with the controls. Similarly, TSH levels were significantly lower in AD and DOC (P < 0.008; 0.038) as compared with the controls.

Conclusion:

Vitamin B₁₂ and folate were significantly low in both AD and VaD patients. Hence, B vitamin supplementation should be considered as possible targets for the therapeutic intervention in dementia.     

Characteristics of behavioral and psychological symptoms in the oldest patients with Alzheimer's disease

Background: Advancing age increases the risk of developing dementia. Recent studies have clarified characteristic cognitive changes in very old patients with dementia. Although non‐cognitive symptoms are frequent in dementia, relatively little attention has been paid to the nature of behavioral and psychological symptoms of dementia (BPSD). Methods: A retrospective review of a database was performed to compare 27 very old patients with Alzheimer's disease (AD) (onset age ≥ 85) with 162 less old patients (onset age < 85). Cognitive decline, ability to carry out activities of daily living (ADL), and overall severity were rated. BPSD were evaluated using a 16‐item questionnaire to the compare frequency of each symptom between old and very old groups. Results: Cognitive decline was equivocal in both old and very old groups. In contrast, very old patients were more impaired in ADL, and BPSD were more frequent in very old patients. Delusions, irritability, and delusional misidentification syndrome were frequent in both groups, but were more prominent in very old patients. Behavioral abnormalities such as excitement, delirium, reversed diurnal rhythm, and wandering were not prominent in old patients, but were frequent in very old patients. Conclusions: Very old AD patients presented more frequent BPSD than old AD patients. Troublesome behavioral abnormalities particularly prominent in the older patients might represent a heavy burden for caregivers.     

Frontotemporal dementia: patient characteristics,cognition, and behaviour

OBJECTIVES: To describe sociodemographic data of patients with frontotemporal dementia (FTD), to compare the cognitive profile of patients with FTD with that of severity-matched patients with Alzheimer's disease using the CERAD neuropsychological battery (CERAD-NP), to investigate the frequency of behavioural disturbances, and to examine the relation between FTD-specific non-cognitive behavioural symptoms of patients with FTD with age and sex. METHODS: Fifty outpatients were diagnosed with FTD according to the Lund-Manchester consensus criteria. Cognitive impairment was assessed in 30 patients using the CERAD-NP. Severity of dementia was rated on the Clinical Dementia Rating (CDR). Eleven non-cognitive symptoms were rated by severity. To compare CERAD-NP results between patients with FTD and AD, 30 patients with AD were matched for age, sex, and global severity of cognitive performance. RESULTS: The average age at onset of first symptoms was 57.8 years. Eighteen patients (36%) had a positive family history of dementia. On the CERAD-NP patients with FTD performed significantly better than patients with AD on word list learning, delayed verbal recall and visuoconstruction (p < 0.05). There were no significant differences between FTD and AD on naming and verbal fluency tasks. The most frequent non-cognitive behavioural symptoms in FTD were loss of insight, speech abnormality, and apathy. Non-cognitive behavioural symptoms were more frequent in younger and in male than in older patients and in female patients. CONCLUSIONS: The CERAD-NP is a valuable clinical instrument for the cognitive evaluation of patients with suspected FTD. Complementary short tests of attention and executive function may be recommended. To enhance diagnostic sensitivity informant interviews should focus on non-cognitive behavioural changes, taking advantage of standardised questionnaires.     

Behavioral correlates of cerebrospinal fluid amino acid and biogenic amine neurotransmitter alterations in dementia

BackgroundBehavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms.MethodsPatients with probable Alzheimer’s disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37), probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection.ResultsIn the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations.ConclusionsSeveral neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well.     

Low B12 levels related to high activity of platelet MAO in patients with dementia disorders. A retrospective study

In 35 patients with Alzheimer's presenile disease (AD), 56 patients with senile dementia of the Alzheimer type (SDAT), 54 patients with vascular dementia (VD) and 10 patients with confusional states, age, vitamin B12 in serum, P-folate, B-folate and B-Hb were investigated. Platelet monoamine oxidase (MAO) and cerebrospinal fluid (CSF) levels of homovanillic acid (HVA), 5-hydroxyin-doleacetic acid and 3-methoxy-4-hydroxyphenylglycol were measured. Group differences showed that vitamin B12 levels were reduced in the group of patients with confusional states and SDAT. Five out of ten and 13 out of 56 (respectively) had vitamin B12 concentrations below the lower limit of the reference value (130 pmol/l). A negative correlation was found between B12 levels and platelet MAO activity. The findings indicate that there is a subgroup of patients with late-onset dementia that has low vitamin B12 blood concentrations. HVA levels in CSF, usually found to be reduced in AD patients, were normal in this subgroup.     

The Middelheim Frontality Score: a behavioural assessment scale that discriminates frontotemporal dementia from Alzheimer's disease

BACKGROUND: Despite striking neuropsychological and behavioural differences between Alzheimer's disease (AD) and frontotemporal dementia (FTD), clinical diagnostic criteria failed to discriminate FTD from AD patients. We therefore developed the Middelheim Frontality Score (MFS), a disease-long clinical and behavioural assessment tool that measures frontal lobe features, and set up this prospective study in clinically diagnosed AD and FTD patients to assess discriminatory power and intra- and inter-rater variability. METHODS: Patients with probable AD (n = 400) and FTD (n = 62) were included. The MFS was obtained by summating the scores obtained in a standardized fashion on ten items yielding a total maximal score of 10. Information was obtained through an interview of the patient and her/his caregiver, clinical files and behavioural observation. RESULTS: Comparing mean total MFS scores, FTD patients (6.3 +/- 1.8) had significantly higher scores than AD patients (3.1 +/- 1.8) (p < 0.001). Distribution of scores on individual MFS items was significantly different between both disease groups (chi(2) = 76.2; p < 0.001). A moderately positive and highly significant correlation was shown between the total MFS score and diagnosis FTD (r = 0.478; p < 0.0001). Applying a total MFS score of 5 as discriminatory cut-off, a specificity of 89.0% and a sensitivity of 88.7% were achieved. Intra- and inter-rater variability was calculated in a different study population by means of retest correlation, revealing moderate to strong positive correlations of high statistical significance. CONCLUSIONS: The MFS is a clinical and behavioural assessment scale that measures frontal lobe features and that was shown to reliably discriminate FTD from AD patients.     

A short neuropsychologic and cognitive evaluation of frontotemporal dementia

Objective

To elaborate a brief but efficient neuropsychological assessment of frontotemporal dementia (FTD), selecting the most specific and sensitive cognitive and behavioural items for distinguish between AD and FTD in the earlier dementia stages.

Methods

Retrospective study with three groups, 35 patients with FTD, 46 with AD and 36 normal subjects, were administered the MMSE, FAB, Tower of London and Stoop's test along with a 98 items behavioural and cognitive questionnaire. The most sensitive items were selected and validated internally for diagnosis by lineal discriminant analysis.

Results

From the 98 items in the questionnaire, 29 showed significant discriminatory power. Non-cognitive symptoms with higher odd-ratio for FTD compared to AD were impairment in social behaviour (disinhibition, aggressiveness), loss of insight and inappropriate acts. Language disorders, such as echolalia, verbal apraxia or aggramatism, dominate in the cognitive profile of FTD. FAB was confirmed as the best cognitive instrument to differentiate FTD and AD. A linear discriminant function with the combination of the FAB score and the items from our questionnaire with higher OR for FTD accurately classified 97% of individuals.

Conclusions

The neuropsychological tests allow the differentiation between FTD and AD. The combination of FAB test with the assessment of key behavioural and cognitive symptoms appears helpful in this distinction.     

Vitamin B(12) and folate in relation to the development of Alzheimer's disease

OBJECTIVE: To explore the associations of low serum levels of vitamin B(12) and folate with AD occurrence. METHODS: A population-based longitudinal study in Sweden, the Kungsholmen PROJECT: A random sample of 370 nondemented persons, aged 75 years and older and not treated with B(12) and folate, was followed for 3 years to detect incident AD cases. Two cut-off points were used to define low levels of vitamin B(12) (< or =150 and < or =250 pmol/L) and folate (< or =10 and < or =12 nmol/L), and all analyses were performed using both definitions. AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria. RESULTS: When using B(12) < or =150 pmol/L and folate < or =10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B(12) or folate had twice higher risks of developing AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B(12) or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B(12) < or =250 pmol/L and folate < or =12 nmol/L. CONCLUSIONS: This study suggests that vitamin B(12) and folate may be involved in the development of AD. A clear association was detected only when both vitamins were taken into account, especially among the cognitively intact subjects. No interaction was found between the two vitamins. Monitoring serum B(12) and folate concentration in the elderly may be relevant for prevention of AD.     

Metacognitive deficits in frontotemporal dementia

OBJECTIVES: To investigate whether metacognitive impairments in self-awareness and self-monitoring occur in patients with frontotemporal dementia (FTD), particularly among those with prominent social and dysexecutive impairments. METHODS: Patients diagnosed with FTD were divided by clinical subtype (social-dysexecutive (n = 12) aphasic (n = 15), and constituent subgroups of progressive non-fluent aphasia and semantic dementia) and compared with subjects with probable Alzheimer's disease (AD, n = 11) and age-matched healthy controls (n = 11). All subjects completed comprehensive behavioural ratings scales, which were compared with caregiver ratings. Subjects also rated their test performances in verbal associative fluency, word list learning, and memory task with comparisons made between actual and judged performance levels. RESULTS: The FTD sample as a whole showed significantly less behavioural self-awareness and self-knowledge than the AD and healthy control samples. FTD patients with prominent social and dysexecutive impairments demonstrated the most extensive loss of self-awareness and self-knowledge, significantly overrating themselves in multiple social, emotional, and cognitive domains, and failing to acknowledge that any behavioural change had occurred in most areas. The remaining clinical samples showed select and minimal discrepancies. All clinical groups were significantly unaware of their apathy levels. Most FTD patients judged episodic cognitive test performance adequately, with partial difficulties observed in the socially impaired and progressive non-fluent aphasia subgroups. CONCLUSIONS: FTD patients, particularly those with prominent social and dysexecutive impairments, exhibit profound metacognitive anosognosia that may represent a loss of self-awareness, self-monitoring, and self-knowledge, likely related to significant prefrontal pathophysiology. Other FTD clinical groups and AD patients showed less pervasive and more select metacognitive deficiencies.     

Post‐marketing survey of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia (BPSD)

Background: To investigate the efficacy and safety of donepezil hydrochloride (Aricept^®; Eisai Co., Ltd, Tokyo, Japan), we conducted a post‐marketing survey in Japanese patients with Alzheimer's disease (AD) who also had behavioral and psychological symptoms of dementia (BPSD), such as hallucinations/delusions, wandering, and aggression, which cause the greatest burden on caregivers. Methods: A prospective, centrally registered investigation was conducted through regular clinical settings with patients diagnosed as mild to moderate AD presenting with hallucinations/delusions, wandering, and/or aggression. The treatment period was 12 weeks and no restrictions were placed on concomitant medications. Results: The BPSD improvement rates at last‐observation‐carried‐forward (LOCF) were 60.1% for hallucinations/delusions, 59.6% for wandering, and 65.6% for aggression. For all symptoms, improvement rates increased with the duration of the treatment period. The BPSD deterioration rates at LOCF were 1.3% for hallucinations/delusions, 3.4% for wandering, and 1.6% for aggression. Assessment of cognitive function with both the revised Hasegawa Dementia Scale (HDS‐R) and Mini‐Mental State Examination (MMSE) indicated significant improvements after treatment. There were significant differences in the changes in HDS‐R scores between patients whose hallucinations/delusions or wandering were improved and patients whose symptoms were not improved. Moreover, the data suggested a possible correlation between changes in hallucinations/delusions and HDS‐R scores, changes in hallucinations/delusions and MMSE scores, and changes in wandering and MMSE scores. Patients in whom BPSD improved also demonstrated a greater improvement in cognitive function compared with patients in whom no improvement in BPSD was noted. Nursing burden on caregivers at LOCF showed 3.6% for ‘No burden’, 54.1% for ‘Burden decreased’, and 4.5% for ‘Burden increased.’ There was an increase in the combined ratio of ‘No burden’ and ‘Burden decreased’ in proportion with prolonged treatment period. Patients with improved BPSD had a significantly greater ratio (88.5–94.4%) of ‘No burden’ plus ‘Burden decreased’ than those patients in whom no improvement in BPSD was noted. Conclusions: These results suggest that donepezil not only improves the cognitive dysfunction of AD patients, but may also relieve BPSD in these patients. Treatment with donepezil was also found to alleviate the burden of caregivers for approximately 60% of patients. Moreover, the results indicate that donepezil is unlikely to trigger potential risks of excessive deterioration of BPSD, which would result in a heavier burden of nursing care.     

BPSD Patterns in Patients With Severe Neuropsychiatric Disturbances: Insight From the RECAGE Study

ObjectiveBehavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD.MethodsWe analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE.ResultsMean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms.ConclusionPatients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology.     

Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients with progressive dementia.

Vitamin B12 deficiency is common in elderly persons, yet its role in dementia and psychiatric illness is unclear. The authors examined the relationship between vitamin B12 serum levels and cognitive and neuropsychiatric symptoms in dementia. Community-dwelling elderly subjects (N=643) meeting NINCDS-ADRDA criteria for probable or possible Alzheimer disease (AD) underwent comprehensive neuropsychiatric evaluation and measurement of vitamin B12 serum levels. Thirty-seven subjects (5.7%) had low B12 serum levels (200 pcg/ml or less). Subjects with low B12 levels were significantly older and had significantly lower scores on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale, but not a different pattern of cognitive or behavior disturbances compared with the normal-B12 subjects. In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment.     

The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia,Lewy body dementia,and Alzheimer's disease: clinical experience in China

Background and aims: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia.

Method: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI).

Results: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients.

Conclusion: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.