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.

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.

Long-term rivastigmine treatment in a routine clinical setting.

OBJECTIVE: The aim of the study was to observe the effects of long-term rivastigmine treatment in patients with mild to moderate Alzheimer's disease (AD) in a routine clinical setting. METHODS: This was a prospective, open-label, observational, multicentre, non-randomized study. Outcome measures included the Mini Mental State Examination (MMSE), the Clinician's Interview-Based Impression of Change (CIBIC) and the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog). RESULTS: Of 217 patients initiated into rivastigmine treatment, 62% (n = 135) remained on treatment for 24 months. Most patients droped out due to nursing home placement or side effects. Eighty per cent and 67% of completers exhibited a symptomatic attenuation of cognitive decline (< or = 4-point deterioration) as assessed by using the MMSE and ADAS-cog respectively. Forty-four per cent showed an unchanged/improved CIBIC rating. CONCLUSIONS: Over 60% of patients remained on treatment for 2 years in this routine clinical setting. In patients who remained on treatment, rivastigmine appeared to stabilize their condition and prevented or delayed symptomatic decline.

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.

Five-year outcome of cholinergic treatment of Alzheimer's disease: early response predicts prolonged time until nursing home placement, but does not alter life expectancy.

Fifty consecutive outpatients with Alzheimer's disease (AD) received treatment with the cholinesterase inhibitor tacrine in an open longitudinal study. Assessments using Mini-Mental State Examination, Alzheimer's Disease Assessment Scale - cognitive subscale, and a global rating were made at baseline and at 6, 12, 24, 36, 48 and 60 months. Three outcome groups were characterized: responders, unchanged and deteriorated. Additional outcome measures were time until nursing home placement, and mortality rate. At 6 months -75%, at 12 months -42%, at 24 months -20%, and after that 10% of the patients still on medication had improved or remained stable. The mortality rate did not differ between the outcome groups. Response to tacrine treatment at 6 or 12 months was found to predict a prolonged time until nursing home placement. No predictors for a positive treatment response could be identified at baseline.

Prevalence of thyroid hormone abnormalities in elderly patients with symptoms of organic brain disease.

Analysis of the serum concentrations of free thyroid hormones (fT3, fT4) and thyrotropin (TSH) in 173 psychogeriatric patients (94 females and 79 males, mean age 79 +/- 8 years) disclosed that the hormone levels were related to sex, psychiatric diagnosis, medication and the presence of nonthyroid illness (NTI). Subnormal concentrations of thyroid hormones and/or TSH were found in 25% of the patients. In addition, fT3 and fT4 concentrations were significantly lower (p < 0.05 and p < 0.001, respectively) in demented males compared with demented females although the levels were within the reference limits. Strongly negative correlations between fT3 and age (p < 0.001), and between fT3 and the sedimentation rate (SR) (p < 0.01) were found in demented but not in non-demented patients. These correlations were most pronounced in (age) or restricted to (SR) demented males. In addition, the correlation between fT3 and Hb was strongly positive (p < 0.001) in demented as well as in nondemented patients, particularly in males. The concentration of fT4 was positively correlated to Hb in demented males (p < 0.001), whereas TSH concentration was positively correlated to Hb in demented females (p < 0.05). The results show that TSH is not sufficient as the sole screening assay for evaluation of possible thyroid dysfunction in psychogeriatric patients. In addition, central (hypothalamic?) hypothyroidism may be present in a substantial amount of psychogeriatric patients, as we found an adequate TSH response to exogenous thyrotropin-releasing hormone (TRH) also in patients with decreased fT3/fT4 and no signs of non thyroid diseases. Furthermore, there was an apparent lack of correlation between thyroid hormone levels and dementia (or subgroups of dementia), even though thyroid hormone abnormalities seemed to be rather common in frontotemporal dementia (38%) and non specified dementia (36%).