Interview with Prof. Paul G. Unschuld

Can you explain what modalities you use to diagnose dementia / AD at your center?

Our diagnostic approach is consistent with internationally established procedures for diagnosis of cognitive disorder and dementia. We apply a multidisciplinary approach, where medical doctors of different specialties, including psychiatry, neurology and geriatric medicine, together with specialized neuropsychologists are involved. Information provided by the family of the patient, and/or care-takers, plays a central role for understanding an individual’s cognitive disorder. This includes information on the development of the disorder, accompanying medical disorders, and nervous system impairment. By means of standardized neuropsychological testing, extent of the cognitive disorder can be investigated. Moreover, information on affected cognitive domains. E. g. for Alzheimer’s dementia, episodic memory impairment would be expected at an early stage of the disease. This clinical information is supplemented by various biomarkers. Biomarkers may provide information on loss of brain tissue, metabolic dysfunction, or evidence of neuropathological change such as amyloid-beta or tau accumulation. For this purpose, we use imaging techniques such as MRI and PET, as well as CNS and blood tests.

Can you describe what “blood biomarkers” are and how they are used to diagnose dementia?

“Blood biomarkers” are based on analytical methods of blood-plasma or serum, for obtaining information regarding neuropathological processes in the central nervous system. This is a field that is currently developing rapidly. Diagnostic precision of blood biomarkers for diagnosis of dementia, and validity for longitudinal follow-up testing, are subject of ongoing trials. At present, there are markers that inform on amyloid-beta, tau and various other proteins implicated in cognitive disorder and dementia. Can you describe how “cerebrospinal fluids” (CSF) works?

Can you describe how “cerebrospinal fluids” (CSF) works?

The cerebrospinal fluid (CSF) surrounds the central nervous system, and can be examined to gather evidence of pathological brain changes. CSF can be obtained for clinical examination by lumbar puncture. Before the development of “blood biomarkers” and modern PET tracers, CSF examination was the only way to obtain information about neuropathological changes in the central nervous system. At the present time, CSF examination has a well established place in the diagnostic workup of dementia.

When do you suggest to use blood biomarkers, CSF or brain PET for dementia / AD diagnosis?

We try to perform brain PET in as many patients as possible, often complemented by CSF analysis. Should there are contraindications against either one, e. g. for reasons of medical comorbidities, diagnostic information may be provided by blood tests.

Can blood Biomarkers and CSF provide information which PET can’t and vice versa?

There are certain blood-biomarkers which can provide information on pathological proteins, for which to my information at this point no PET tracers are available for clinical use. These include TDP-43 and also Neurofilament light (NfL). A valuable information of PET is the spatial distribution of pathological change: E.g. to know the extent to which vulnerable areas such as temporal cortex are affected by tauopathy. This might be particularly helpful for understanding brain change in early stages of Alzheimer’s disease.