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Objective: The overall aim was to evaluate to what extent the diagnosis of dementia subtypes, obtained by three clinical rating scales, concurred with postmortem neuropathologic (NP) diagnosis of Alzheimer disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and mixed AD/VaD., Design: A prospective longitudinal clinical work-up with postmortem NP examination., Participants: Two hundred nine patients with dementia referred for clinical evaluation and follow-up., Methods: The diagnostic scores in a set of three short clinical rating scales for AD, FTD, and VaD were evaluated against NP diagnoses., Results: The sensitivity and specificity of the AD scale were 0.80 and 0.87, respectively, of the FTD scale 0.93 and 0.92, respectively, and of the Hachinski Ischemic Score (HIS, VaD diagnosis) 0.69 and 0.92, respectively. Cases with mixed AD/VaD generally presented a combination of high AD and ischemic scores. A preferred cutoff score of six was identified for both the AD and FTD scales., Conclusions: All three clinical rating scales showed a high sensitivity and specificity, in close agreement with final NP diagnosis-for the HIS a moderate sensitivity. These scales may thus be considered good diagnostic tools and are recommended for clinical and research center settings.

Background: Clinical dementia diagnoses are not always consistent with neuropathological findings. As correct diagnosis is important for treatment and care, new diagnostic possibilities for dementia are in demand. Cerebrospinal fluid biomarkers should ideally be able to identify ongoing processes in the brain, but need to be further compared with neuropathological findings for evaluation of their diagnostic validity., Methods: This study included 43 patients with a clinical dementia disorder. All patients were neuropathologically examined at the University Hospital in Lund, Sweden, during the years 2001-2008, and all had a lumbar puncture carried out as part of the clinical investigation during the time of cognitive impairment., Results: Of eight patients, five with Alzheimer's disease had elevated total tau protein (T-tau) and decreased amyloid beta 1-42 protein (Abeta42), while both values for the other three patients were normal. Slightly elevated T-tau and/or decreased Abeta42 were also seen in several patients with other dementia diagnoses such as Lewy body disease, frontotemporal lobar degeneration and vascular dementia. Furthermore, T-tau levels did not differ markedly between patients with morphologically tau-positive and tau-negative frontotemporal lobar degeneration. Also, seven of nine patients with Creutzfeldt-Jacob disease exhibited pronounced elevation in T-tau concentration., Conclusion: From this rather limited study, being the first of its kind in Sweden, we may conclude that there is no perfect concordance between cerebrospinal fluid biomarker levels and pathological findings, which should be taken into account in the clinical diagnostic setting., (2010 The Alzheimer's Association. All rights reserved.)

We investigated the distribution of neuropathologically defined dementia subtypes among individuals with dementia disorder. The neuropathological reports were studied on all patients (n=524; 55.3% females; median age 80, range 39-102 years) with clinically diagnosed dementia disorder who underwent complete autopsy including neuropathological examination within the Department of Pathology at the University Hospital in Lund, Sweden, during the years 1974-2004. The neuropathological diagnosis was Alzheimer's disease (AD) in 42.0% of the cases, vascular dementia (VaD) in 23.7%, dementia of combined Alzheimer and vascular pathology in 21.6%, and frontotemporal dementia in 4.0% of the patients. The remaining 8.8% of the patients had other dementia disorders, including combinations other than combined Alzheimer and vascular pathology. The registered prevalence of dementia subtypes depends on many variables, including referral habits, clinical and neuropathological judgments and diagnostic traditions, all of these variables potentially changing over time. This, however, does not seem to obscure the delineation of the major dementia subgroups. In this material of 30 years from Lund in the south of Sweden, AD by far dominated among dementia subtypes, while cerebrovascular pathology corresponded with the dementia disorder, either entirely or partly, in almost half of the demented patients.

Clinical vascular features, either as manifest vascular disease or as cardiovascular risk factors were compared in AD with and without neuropathological white matter disease (WMD). The aim of the study was to investigate whether the presence of WMD and the severity of either AD pathology or WMD were associated with different cardiovascular profiles. A total of 44 AD cases were retrospectively studied. All the cases were neuropathologically diagnosed as AD with WMD (n=22) and as AD without WMD (n=22), respectively. The patients' medical records were studied with regard to their medical history and to somatic and neurological findings including arrhythmia, congestive heart failure, angina, myocardial infarctions, signs of TIA/stroke, diabetes mellitus, and blood pressure abnormalities, such as hypertension and orthostatic hypotension. In AD-WMD, hypertension, orthostatic hypotension as well as dizziness/unsteadiness were significantly more common than in AD without WMD. Cardiovascular symptoms were more frequent in AD-WMD than in the other group, though the difference did not reach statistical significance. Hypothetically, abnormal and unstable blood pressure levels underlie recurrent cerebral hypoperfusion, which may in turn leave room for the development of WMD. Furthermore, dizziness/unsteadiness may be a symptom reflecting the presence of WMD.

Aims: To study cardio-cerebrovascular disease and clinical features, such as falls, dizziness/unsteadiness, urinary incontinence, hallucinations/delusions and delirium in neuropathologically defined subgroups of vascular Dementia (VaD): pure Small Vessel Dementia (SVD), combined SVD and Alzheimer's disease (SVD-AD), pure Large Vessel Dementia (LVD) and pure Hypoxic Hypoperfusive Dementia (HHD), and to analyse the clinical differences between these groups., Materials and Methods: From 175 consecutive cases with neuropathologically verified VaD cases with pure SVD (n = 36) and SVD-AD (n = 38) with varying severity of AD pathology were selected and studied with respect to cardio-cerebrovascular and other clinical features. Furthermore, a comparison between pure SVD, pure LVD (n = 7) and pure HHD (n = 6) was made., Results: Neither cardiovascular symptoms, hypertension, Transitoric Ischemic Attacks (TIA) nor complete cerebrovascular lesions (CVL) differed significantly between the pure SVD and SVD-AD groups. However, a wide variation of clinical features were reported. The prevalence of cardiovascular features varied markedly in the pure groups, with the highest prevalence consistently found in the LVD group. Hypertension was common in the pure LVD and SVD-groups, while it was a rare finding in the HHD-group. TIA and/or CVL were, as expected, most common in the LVD-group., Conclusion: In conclusion, this longitudinal and retrospective study of VaD shows important clinical similarities as well as differences between pathologically defined subgroups. Hopefully these findings will contribute to a better understanding of etiopathogenetic and diagnostic issues and form a solid basis for possible treatment strategies in VaD., (Copyright 2006 John Wiley & Sons, Ltd.)

All vascular dementia (VaD) cases, neuropathologically verified in a longitudinal prospective dementia project, were classified according to the vascular brain lesion type and related to the dementia type and cardiovascular pathology. From 1976 to 1995, there were 175 VaD cases, 49 of which were pure, without Alzheimer pathology and only one type of cerebrovascular lesion. Furthermore, it was found that 6 cases suffered hypoxic hypoperfusive disease, while 7 were found to have large vessel disease and 36 small vessel disease. In addition to Alzheimer pathology, more than one type of vascular brain pathology was found in the remaining 126 cases. In these cases, diagnosed in accordance with the predominant type of VaD, hypoxic-hypoperfusive lesions were found in 55, large vessel lesions in 50 and small vessel lesions in 110 cases. It should be stressed that 87% of all cases with hypoxic hypoperfusive lesions also had Alzheimer pathology. Cardiovascular and aortic pathologies were more prevalent in small vessel dementia than in the other VaD groups. Clinically diagnosed arterial hypertension was significantly associated with small vessel dementia, but not with hypoxic-hypoperfusive dementia. Cardiovascular symptoms varied considerably in frequency between different dementia groups. VaD is a heterogeneous group regarding lesions caused by different pathophysiological mechanisms and with different combinations of brain pathologies. It is therefore necessary to identify the various types of vascular brain lesions for a correlation with clinical symptoms and for diagnostic purposes in the search for risk factors and therapeutic strategies., (Copyright 2005 S. Karger AG, Basel.)