Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)68880-6.pdf

Mild cognitive impairment

Tau protein isoforms, phosphorylation and role in neurodegenerative disorders

Article abstract—Objective: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. Background: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. Methods: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? Recommendations: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke‐AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt‐Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B12 deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). Conclusions: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.

https://n.neurology.org/content/neurology/56/9/1143.full.pdf

Practice parameter: Diagnosis of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology

Summary Early diagnosis of Alzheimer's disease (AD) is needed to initiate symptomatic treatment with acetylcholinesterase inhibitors, and will be of even greater significance if drugs aimed at slowing down the degenerative process, such as vaccination regimes and β-secretase and γ-secretase inhibitors, prove to affect AD pathology and to have clinical effect. However, there is no clinical method to determine in which patients mild cognitive impairment (MCI) will progress to AD with dementia, and in which patients MCI is benign. Hence, there is a great clinical need for biomarkers to identify incipient AD in patients with MCI. The CSF biomarkers total tau protein, phosphorylated tau protein, and the 42 amino-acid residue form of amyloid-β may, if put in the right clinical context, prove to have high enough diagnostic accuracy to meet this challenge.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(03)00530-1.pdf

CSF markers for incipient Alzheimer's disease

This study evaluated an automated analysis of SPECT brain imaging in patients with Alzheimer9s disease (AD). Methods: Patients [n =81; mean age, 69.9 ± 10.6 yr (mean ± s.d.)] with a clinical diagnosis of probable AD (NINCDS-Alzheimer9s Disease and Related Disorders Association criteria) underwent 99mTc-ethyl cysteine dimer SPECT imaging. After imaging registration and data extraction using three-dimensional stereotactic surface projections, a pixel-wise comparison of ethyl cysteine dimer uptake was performed using a reference database of 10 cognitive intact controls of comparable age. Results: When individual cases were compared to the normal database, tempora-parietal regional cerebral blood flow (rCBF) abnormalities across different levels of dementia severity were clearly depicted on pixel-wise Z-score images. The rCBF reduction incortical association areas showed a significant correlation with an overall level of cognitive decline, as assessed by the Mini Mental State Examination and by the cognitive section of the Cambridge Mental Disorders of the Elderly Examination. In addition, there were significant region-specific correlations between left temporo perfusion deficit and language performance and between right parietal rCBF reduction and praxis. Conclusion: These results indicate that this observer-independent analysis of SPECT data enables objective and semiquantitative assessment of the magnitude and extentof cortical perfusion abnormalities in patients with AD.

https://jnm.snmjournals.org/content/jnumed/38/7/1095.full.pdf

Quantitative Assessment of Cerebral Blood Flow in Patients with Alzheimer's Disease by SPECT

Cerebrospinal protein tau is elevated in early Alzheimer's disease

The aim of the study was to evaluate an observer-independent semiquantitative analysis of brain imaging by single-photon emission computed tomography (SPECT) in patients with Alzheimer''s disease (AD)

Reduction of regional cerebral blood flow and cognitive impairment in patients with Alzheimer's disease: evaluation of an observer-independent analytic approach.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673605625688.pdf

Diagnosis of Alzheimer's disease with cerebrospinal fluid tau protein and aspartate aminotransferase

In 40 patients with Alzheimer's disease (AD), in 5 patients with non-AD dementia and in 36 cognitively normal controls the concentration of protein tau was determined in the cerebrospinal fluid (CSF). Of the AD patients, 19 were very mildly demented (MMSE score from 25 to 28). Even in these patients, CSF tau was significantly more elevated than in controls. In the non-AD patients protein tau was less increased. Among the AD patients there was no association between CSF tau and severity of cognitive impairment or deficit in cerebral blood flow, determined by SPECT. Our findings suggest that CSF tau may be elevated even at the predementia stage of AD and be useful as a biological marker for the early recognition of the disease.

Katharina Buch

Papers

Quantitative Assessment of Cerebral Blood Flow in Patients with Alzheimer's Disease by SPECT

Cerebrospinal protein tau is elevated in early Alzheimer's disease

Reduction of regional cerebral blood flow and cognitive impairment in patients with Alzheimer's disease: evaluation of an observer-independent analytic approach.

Diagnosis of Alzheimer's disease with cerebrospinal fluid tau protein and aspartate aminotransferase

Tau protein. A potential biological indicator for early detection of Alzheimer disease