Lack of orthostatic symptoms in dementia patients with orthostatic hypotension.

PURPOSE: Orthostatic hypotension (OH) is common and increases with age. OH is part of the autonomic dysfunction in dementia with Lewy bodies (DLB). Commonly OH is diagnosed when the patient falls which is a risk factor of premature death. Our objective was to systematically investigate the clinical symptoms associated with measurement of OH in different neurodegenerative dementias and normal controls (NC). METHODS: 154 patients [50 DLB, 50 Alzheimer's disease (AD), 54 AD and vascular components (ADvasc)] were examined with systolic and diastolic blood pressure measurements in supine position, immediately after standing up and after 1, 3, 5 and 10 min of standing. They were compared with 50 NC. Orthostatic symptoms were registered according to a predefined protocol. RESULTS: Twenty-seven percent of all the investigated individuals reported OH symptoms during the measurement while 43% fulfilled the criteria of OH. Sixty-three percent of orthostatic patients did not have any symptoms during the measurement. The prevalence of any orthostatic symptoms during the measurement differed significantly (p < 0.001) between the diagnostic groups with 40% in DLB patients, 37% in ADvasc, 28% in AD and 2% in NC. The most frequent symptom was dizziness 13.7%. CONCLUSIONS: Classical orthostatic symptoms are absent in the majority of dementia patients with OH. The orthostatic reaction must therefore be routinely measured in this patient group. This is particularly important for patients with DLB where falls as a result of OH are common.

Efficacy of memantine in PDD and DLB: an extension study including washout and open-label treatment.

OBJECTIVE: This 30-week extension trial was a continuation of the first double-blind randomized controlled trial (RCT) to study memantine in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The objective was to evaluate the presence of recurrence of symptoms upon drug withdrawal. Furthermore, the aim was to explore washout dynamics in order to inform clinical practice. METHODS: Patients were enrolled from psychiatric, memory and neurological outpatient clinics in Norway, Sweden and the UK. The trial comprised a 4-week washout period and a 26-week open-label treatment period. Outcome measures were presence of recurrence of symptom upon drug withdrawal, Clinical Global Impression of Change (CGIC) and modified motor Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: recurrence of symptoms occurred more frequently (p=0.04) in patients receiving memantine (58%) than in patients receiving placebo (25%). There was a significant global deterioration (p=0.0003) during washout within the memantine group as measured by CGIC. The patients seemed to recover during the open-label treatment, however these findings were non-significant. CONCLUSIONS: The findings inform clinical practice that any possible memantine-associated benefits might be rapidly lost after drug withdrawal. The magnitude of deterioration suggests a symptomatic rather than a disease-modifying effect of the drug. Open-label results should merely be considered inspiration for future trials.

The cognitive profile and CSF biomarkers in dementia with Lewy bodies and Parkinson's disease dementia.

OBJECTIVE: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) may be viewed as different points on a continuum reflecting the regional burden and distribution of pathology. An important clinical consideration is overlapping Alzheimer's disease (AD) pathology, since it has been reported that associated AD pathology in DLB shortens survival and leads to a more rapid cognitive decline. We aimed to investigate cerebrospinal fluid (CSF) biomarkers and the associated cognitive profile in DLB and PDD. METHODS: Clinically diagnosed DLB (n=47) and PDD (n=17) patients from a clinical follow-up programme were investigated. All performed mini mental state examination (MMSE) and went through lumbar puncture at baseline. CSF concentrations of total τ (T-τ), τ phosphorylated at threonine 181 (P-τ(181) ) and the 42 amino acid isoform of amyloid ß, Aß42 were determined. RESULTS: We found significant differences in T-τ and Aß42, with a higher level of T-τ and a lower level of Aß42 in DLB compared to PDD. The combination of T-τ with Aß42 showed better discrimination between DLB and PDD than either of the measures alone. In DLB, a CSF profile more like the one seen in AD was significantly correlated with worse performance on the orientation and memory of the MMSE. CONCLUSION: The correlation suggests a possible link between a higher degree of AD pathology and a profile of more temporal disabilities on cognitive tests in DLB. This might aid in identifying a subgroup of patients with a greater burden of AD pathology in a clinical setting and could have important implications for prognosis.

CSF biomarkers predict a more malignant outcome in Alzheimer disease.

OBJECTIVE: To investigate if patterns of CSF biomarkers (T-tau, P-tau, and Abeta42) can predict cognitive progression, outcome of cholinesterase inhibitor (ChEI) treatment, and mortality in Alzheimer disease (AD). METHODS: We included outpatients with AD (n = 151) from a prospective treatment study with ChEI. At baseline, patients underwent cognitive assessments and lumbar puncture. The patients were assessed longitudinally. The 5-year survival rate was evaluated. CSF-Abeta42, T-tau, and P-tau were analyzed at baseline. K-means cluster analysis including the 3 CSF biomarkers was carried out. RESULTS: Cluster 1 contained 87 patients with low levels of Abeta42 and relatively low levels of T-tau and P-tau. Cluster 2 contained 52 patients with low levels of Abeta42 and intermediate levels of T-tau and P-tau. Cluster 3 contained 12 patients with low levels of Abeta42 and very high levels of CSF T-tau and P-tau. There were no differences between the clusters regarding age, gender, years of education, baseline instrumental activities of daily living, or APOE genotype. Even though there was no difference between cluster 3 and the other clusters in disease duration or global rating, the patients in cluster 3 performed worse on cognitive tests already at baseline. Patients in cluster 3 exhibited a very poor outcome of ChEI treatment. Finally, cognition deteriorated faster over time and the mortality rate was substantially increased in cluster 3. CONCLUSION: A subgroup of patients with Alzheimer disease with extreme levels of CSF biomarkers exhibits worse clinical outcomes over time, including faster progression of cognitive deficits, no response to ChEI treatment, and a higher mortality.

Medial temporal lobe atrophy increases the specificity of cerebrospinal fluid biomarkers in Alzheimer disease with minor cerebrovascular changes.

BACKGROUND: Although cerebrospinal fluid (CSF) biomarkers and medial temporal lobe atrophy (MTA) contribute to the diagnosis of Alzheimer disease (AD), they may not be specific. Relatively little is known about how they correlate with each other. PURPOSE: To identify the validity of the radiological linear measurements of brain atrophy in AD diagnosis by examining the correlation with CSF biomarkers and by examining if specificity could be improved in classification of AD from controls, when the linear measurements are combined with the CSF biomarkers. MATERIAL AND METHODS: 59 controls (20 male/39 female, age 73+/-8 years), 162 pure AD patients (49/113, 74+/-7 years), and 86 AD patients with minor cerebrovascular changes (CVC) (31/55, 77+/-5 years), aged between 52 and 94 years, were recruited from the Malmo Alzheimer Study. AD patients were subgrouped into "pure AD" and "AD + CVC" in order to clarify the possible influence of CVC on atrophy or CSF biomarkers in AD patients. Abeta42, T-tau, and P-tau in CSF were examined. Computed tomography (CT) linear measurements were performed, which included temporal horn ratio and suprasellar cistern ratio that reflect MTA. RESULTS: Compared with the 14 significant correlations between the CT measurements and three CSF biomarkers in the pure AD group, there was only one significant correlation in the AD + CVC group and one in the control group. In particular, P-tau correlates with temporal horn ratio only in pure AD. When the CT measurements were added with CSF biomarkers as independent variables in discriminant analysis, the percentage of correct classification of AD + CVC from controls increased from 79.5% (only CSF biomarkers) to 84.6% (combined CT measurements with CSF biomarkers). However, little was changed in the pure AD group. CONCLUSION: P-tau correlates with the linear CT measure of MTA only in pure AD without CVC. Combined with the measure of MTA, the specificity of CSF biomarkers can be increased, but only in AD + CVC. The linear measurements of MTA are of value in AD diagnosis.

Can CSF biomarkers or pre-treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease?

OBJECTIVE: The main objective of this study was to investigate possible predictors of response to cholinesterase inhibitor (ChEI) treatment, including pre-treatment progression rates and levels of the cerebrospinal fluid (CSF) biomarkers. A secondary objective was to evaluate whether treatment with ChEI changed progression. METHODS: Out-patient individuals (n = 191) with the clinical diagnosis of Alzheimer's disease received ChEI treatment and were part of the Swedish Alzheimer Treatment Study (SATS), a prospective, longitudinal, non-randomised study in a routine clinical setting. Patients were assessed with MMSE, ADAS-cog and a global rating (CIBIC) at baseline, 2 months and every 6 months for a total period of 3 years. The following potential predictors of treatment response were investigated: age, gender, APOE epsilon 4 carrier, education, duration of disease, cognitive level, pre-treatment progression rate (in MMSE) and the levels of the CSF biomarkers A beta 42, T-tau and P-tau. RESULTS: Fast pre-treatment progression rate was a predictor of treatment response even after adjusting for baseline severity, another positive predictor of response. Patients in the fastest quartile of pre-treatment progression rates were significantly more prone to be responders at 2 months (adjusted OR 6.6, p = 0.001) and 6 months (adjusted OR 10.4, p < 0.001) than those in the slowest progressing quartile. Moreover, the linearity of progression was significantly changed by ChEI treatment at 6 months compared to the pre-treatment period. CONCLUSION: The rate of pre-treatment progression was the most consistent positive predictor of ChEI treatment response in the routine clinical setting. The progression rate was significantly changed by ChEI treatment.

Electroencephalogram variability in dementia with lewy bodies, Alzheimer's disease and controls.

BACKGROUND/AIM: Dementia with Lewy bodies (DLB) is probably still underdiagnosed in the clinical setting. Previous studies have suggested a relationship between fluctuations in attention and electroencephalogram (EEG) measures. Since fluctuation in attention is a core symptom of DLB, we sought to further explore whether EEG measures could help differentiate DLB from Alzheimer's disease (AD) and healthy controls. METHODS: The EEGs of 20 patients with DLB, 64 patients with AD and 54 elderly controls were assessed in regard to frequencies, coherence, and variability. RESULTS: Greater variability was seen in delta-band power over 2-second intervals in parietal electrodes of DLB patients. The DLB group had a higher degree of overall coherence in the delta band and a lower degree of overall coherence in the alpha band than the other groups. Finally, EEG measures could distinguish DLB patients from AD patients and controls with areas under the receiver operating characteristic curves ranging between 0.75 and 0.80 and between 0.91 and 0.97, respectively. CONCLUSIONS: We suggest that the difference in variability may be associated with the fluctuating cognition seen in DLB. This might have clinical implications as guidance in the diagnosis of DLB. The EEG analysis is simple enough to be possible to apply in clinical practice.

Pathogenesis of autoimmune diseases: antibodies against transglutaminase, peptidylarginine deiminase and protein-bound citrulline in primary Sjögren's syndrome, multiple sclerosis and Alzheimer's disease.

Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific residues of gliadins have been identified. A similar situation is seen in rheumatoid arthritis (RA) with both anti-citrullinated protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme, peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. Our hypothesis is challenged by findings in patients of primary Sjögren's syndrome (pSS) who do not express ACPA, but who have been reported to carry anti-PAD. The aims of our investigation were to reproduce the study claiming the presence of anti-PAD in pSS and screen for ACPA and antibodies against TG2 and PAD in pSS (n = 78), multiple sclerosis (MS) (n = 85) and Alzheimer's disease (AD) (n = 79) using ELISA. With blood donors (n = 100) as controls, no increased occurrence of autoantibodies was found among the patient groups tested. Contrary to what has been published previously, patients with pSS do not express anti-PAD. The hypothesis of a complex between an enzyme and its modified substrate constituting the neoantigen in autoimmune diseases is still valid. The prevalence of anti-PAD, anti-TG2 and ACPA is comparatively restricted. PAD and TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD.

Prediction of Alzheimer's disease using a cerebrospinal fluid pattern of C-terminally truncated beta-amyloid peptides.

BACKGROUND: Identifying individuals at high risk of developing Alzheimer's disease (AD) is important for future therapeutic strategies, and there is a clinical need for diagnostic biomarkers to identify incipient AD. OBJECTIVE: The aim of the present study was to investigate if the AD-associated Abeta peptide pattern recently found in cerebrospinal fluid (CSF) could discriminate between patients with incipient AD and those with stable mild cognitive impairment (MCI) by analyzing CSF from patients with MCI at baseline. METHODS: The levels of Abeta(1-37, -38, -39, -40, -42) were analyzed by Abeta-SDS-PAGE/immunoblot in CSF from 19 healthy controls, 25 patients with stable MCI and from 25 patients with MCI who later developed AD during 4- to 6-year follow-up. RESULTS: All healthy controls and 20 out of 22 patients who developed AD were correctly classified by their baseline Abeta peptide pattern. In 9 out of 25 stable MCI patients, the pattern indicated incipient AD in spite of clinical nonconversion. Interestingly, these individuals had apolipoprotein E genotypes and CSF levels of tau and phospho-tau that are known to be associated with high risk of AD. CONCLUSION: Altogether, our study reveals the novel finding that the Abeta peptide pattern is able to predict AD in patients with MCI with a sensitivity of 91% and specificity of 64%. The specificity would increase to 94% if the high-risk patients in the stable MCI cohort developed AD during extended follow-up.

Usefulness of computed tomography linear measurements in diagnosing Alzheimer's disease.

BACKGROUND: Medial temporal lobe atrophy (MTA) is an early sign of Alzheimer's disease (AD). The current method of choice for measuring MTA is volumetric measurement based on 3D magnetic resonance imaging (MRI), but this complicated method has not been implemented clinically. PURPOSE: To investigate whether simple computed tomography (CT) linear measurements of the brain could be of value in AD workup. MATERIAL AND METHODS: Fifty-nine healthy control subjects and 248 AD subjects were recruited. They were evaluated using a comprehensive clinical workup. A series of linear CT measurements were obtained from brain CT. RESULTS: In discriminant analysis, the temporal horn ratio and the suprasellar cistern ratio were the atrophy factors that contributed most significantly to the diagnoses. Combined with other clinical factors (apolipoprotein E4 genotype), a correct AD classification of 90.2% was achieved. CONCLUSION: CT linear measurements could be of value in the workup of AD patients, considering the inexpensiveness and availability of CT as well as the simplicity of linear measurements.

Effects of a goal-oriented rehabilitation program in mild cognitive impairment: a pilot study.

BACKGROUND: Memory disturbance, deficient concentration, and fatigue are symptoms seen in amnestic mild cognitive impairment (MCI) as well as in mild traumatic brain injury (TBI). The aim of this study was to assess if an established rehabilitation program commonly used in TBI can aid MCI patients to develop compensatory memory strategies that can improve their cognition, occupational performance, and quality of life (QoL). METHODS: Fifteen patients with MCI participated in the program 2 days per week for 8 weeks. Cognitive function, occupational performance, and self-perceived QoL were assessed at baseline, at the end of the intervention, and at follow-up after 6 months. RESULTS: Significant improvements were seen in cognitive processing speed, occupational performance, and in some of the QoL domains. CONCLUSION: As this goal-oriented rehabilitation program in MCI resulted in some improvements in cognition, occupational performance, and QoL, further randomized controlled studies are warranted.

The period of hypotension following orthostatic challenge is prolonged in dementia with Lewy bodies.

OBJECTIVES: To determine whether orthostatic hypotension (OH) is more common in patients with dementia than in older people without cognitive impairment and to identify key differences in the profile of the orthostatic response and the pulse drive during orthostatic challenge between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: The orthostatic response was evaluated in 235 patients with AD, 52 patients with DLB and 62 elderly controls. The blood pressure and pulse rate were measured in supine position, immediately after standing up and after 1, 3, 5 and 10 min of standing. OH was defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or a reduction of diastolic blood pressure (DBP) of at least 10 mm Hg. RESULTS: OH occurred in 69% of the DLB patients and in 42% of the AD patients, but only in 13% of the controls (p<0.001 controls vs AD and controls vs DLB, p=0.001 AD vs DLB) The DLB patients had a greater drop in SBP than the other study groups during orthostatic challenge and had a more prolonged period of orthostasis. The pulse drive on orthostatic challenge was similar in between groups. However, in the DLB group it was not adequate to restore the blood pressure to supine values. CONCLUSIONS: Patients with DLB react different to orthostatic challenge than patients with AD or controls, with important clinical implications for key disease symptoms and treatment.

Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies.

OBJECTIVE: Serine protease inhibitors (serpins), the acute phase reactants and regulators of the proteolytic processing of proteins, have been recognized as potential contributors to the pathogenesis of Alzheimer disease (AD). We measured plasma and CSF levels of serpins in controls and patients with dementia. METHODS: Using rocket immunoelectrophoresis, ELISA, and Luminex xMAP technology, we analyzed plasma levels of alpha(1)-antichymotrypsin and alpha(1)-antitrypsin, and CSF levels of alpha(1)-antichymotrypsin, alpha(1)-antitrypsin, and neuroserpin along with three standard biomarkers (total tau, tau phosphorylated at threonine-181, and the A beta(1-42)) in patients with AD (n = 258), patients with dementia with Lewy bodies (DLB; n = 38), and age-matched controls (n = 37). RESULTS: The level of CSF neuroserpin was significantly higher in AD compared with controls and DLB, whereas CSF alpha(1)-antichymotrypsin and alpha(1)-antitrypsin were significantly higher in both AD and DLB groups than in controls. Results from logistic regression analyses demonstrate a relationship between higher CSF levels of alpha(1)-antichymotrypsin and neuroserpin and increased predicted probability and odds ratios (ORs) of AD (OR 5.3, 95% CI 1.3 to 20.8 and OR 3.3, CI 1.3 to 8.8). Furthermore, a logistic regression model based on CSF alpha(1)-antichymotrypsin, neuroserpin, and A beta(1-42) enabled us to discriminate between AD patients and controls with a sensitivity of 94.7% and a specificity of 77.8%. CONCLUSIONS: Higher CSF levels of neuroserpin and alpha(1)-antichymotrypsin were associated with the clinical diagnosis of Alzheimer disease (AD) and facilitated the diagnostic classification of AD vs controls. CSF serpin levels did not improve the diagnostic classification of AD vs dementia with Lewy bodies.

Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Contributions of other brain pathologies in dementia with lewy bodies.

The clinical picture with its pathological correlate was analysed in 16 patients fulfilling consensus criteria for dementia with Lewy bodies (DLB). The cases were part of a larger cohort (n = 200) of patients within a prospective longitudinal study of dementing disorders. Six cases exhibited not only Lewy bodies (LBs) but also other brain pathologies such as Alzheimer changes, multiple infarcts or complete and incomplete white matter infarcts. Degeneration of the nucleus basalis of Meynert and substantia nigra was also seen. The 10 cases without LBs all had Alzheimer changes. In 7 cases, these changes were combined with mainly incomplete frontal white matter infarcts. However, the degeneration of brain stem nuclei was less pronounced in these cases. Symptoms such as fluctuations in cognition, falls and episodic confusion appeared in association with arterial hypotension, which developed during the course of dementia in almost all the 16 cases. The majority of the cases were treated with neuroleptics and other potentially hypotensive medication. This study shows that multiple and different pathological features may contribute to a clinical symptom constellation as in DLB. The case study approach reveals the complexity of the clinico-pathological relationships in dementia that might otherwise be lost in the analysis of larger group data.

Neuropathological correlates to clinically defined dementia with Lewy bodies.

OBJECTIVES: To analyse the neuropathological changes behind clinically defined dementia with Lewy bodies (clinDLB) compared with clinically diagnosed Alzheimer's disease (clinAD). METHODS: The prevalence of neuropathological findings in 48 clinDLB and 45 clinAD cases was compared. Sixteen clinDLB and 10 clinAD cases were reassessed with alpha-synuclein staining for Lewy bodies (LB). RESULTS: Alzheimer pathology was found in 81% of the clinDLB and 93% of the clinAD cases. The clinDLB group had a higher prevalence of frontal white matter pathology, mostly of ischemic type, and a more severe degeneration of the substantia nigra compared with the clinAD group. In hematoxylin-eosin staining, LBs were identified in seven (15%) of the clinDLB and in four (9%) of the clinAD group. In alpha-synuclein staining, 38% of the clinDLB and 40% of the clinAD cases exhibited LBs. The cases without LBs, in the clinDLB group, had AD pathology in combination with frontal white matter disease. Vascular pathology of significant degree was prevalent in more than 40% of all the cases with verified LBs regardless of clinical diagnosis. CONCLUSION: Consecutive dementia cases, fulfilling the clinical consensus criteria for DLB, may exhibit combinations of neuropathological changes which in themselves can explain the clinical picture of DLB even when LBs are absent.

Clinical Lewy body dementia and the impact of vascular components.

OBJECTIVE: To study the prevalence of patients fulfilling the clinical consensus criteria for dementia with Lewy bodies (DLB) in a dementia population followed up with postmortem examination. To compare the clinical and neuropathological findings in the clinical Lewy body dementia (LBD) group with findings in a clinically defined group with Alzheimer's disease (AD). DESIGN: Medical records from 200 patients were studied retrospectively. Clinical consensus criteria for DLB and clinical criteria for other dementias were applied. SETTING: The majority of the cases were examined and cared for in psychogeriatric and psychiatric departments. PATIENTS: The patients, who died between 1985 and 1994, were part of a longitudinal dementia project. Each case was neuropathologically examined. Main outcome measures Prevalence of clinical signs and neuropathology was compared between the clinical groups. RESULTS: Forty-eight (24%) patients fulfilled the clinical criteria for DLB while 45 (22%) fulfilled the clinical criteria for Alzheimer's disease. The clinical LBD group had a higher Hachinski score compared to the clinical AD group. They also showed a tendency towards a 'frontal profile' with disinhibition, confusion, personality change and vocally disruptive behaviour. More than 80% of the AD and LBD groups respectively exhibited Alzheimer pathology. The LBD group had frontal white matter pathology and degeneration of the substantia nigra more often than the clinical AD group. Both LBD and AD groups showed a progressive and marked increase in severity of dementia and decrease in ADL capacity according to an evaluation based on the Berger scale and Katz index. The condition of the LBD group was significantly worse earlier in dementia. CONCLUSION: The results of this study indicate that patients fulfilling the clinical criteria for DLB also exhibit clinical features of possible vascular origin and a frontal profile. Subcortical vascular pathology, nigral degeneration and AD pathology in this group could partly explain the clinical features used to define DLB.

Blood pressure and drug treatment in clinically diagnosed Lewy body dementia and Alzheimer's disease.

The aim of the study was to investigate arterial blood pressure (BP) and the use of pharmacological treatment in patients with Lewy body dementia (cLBD) and Alzheimer's disease (cAD) diagnosed on clinical grounds. BP and pharmacological treatment was analysed based on the medical records of 200 deceased dementia patients. Forty-eight cases with LBD and 45 AD were diagnosed using clinical criteria. The patients, who died between 1985 and 1994, were part of a prospective longitudinal dementia project. The majority of the cases were examined and cared for at the psychogeriatric and psychiatric departments. BP levels were very similar at an early stage of dementia but there was a marked decrease during the course of dementia in cAD and cLBD. The cLBD cases became hypotensive during the course of dementia to a significantly greater extent and also had a more pronounced drop in systolic BP at orthostatic testing compared to the cAD cases. cLBD and cAD were prescribed neuroleptics and medication potentially associated with hypotension to the same extent. The total number of these drugs was however higher in cLBD than in cAD. Antiparkinsonian treatment was, as expected, more common in cLBD compared to cAD. The findings suggest that insufficient BP regulation and drug treatment could affect the clinical picture of dementia, particularly in cLBD patients.