Structural imaging markers for therapeutic trials in Alzheimer's disease

Evaluation of a Calibrated 18F-FDG PET Score as a Biomarker for Progression in Alzheimer Disease and Mild Cognitive Impairment

“…MRI morphometry is another promising imaging biomarker for diagnosis and monitoring of progression (6), and a substantial increase of power, compared with ADAS-cog, has been demonstrated (15,32). In contrast to 18 F-FDG PET, results are based entirely on structural imaging and therefore are not influenced by actual synaptic function and pharmacodynamic effects, which facilitates the separation of progression from these functional effects.…”

“…These changes become detectable in individual subjects as significant deviation from controls 1-2 y before onset of dementia and are closely related to cognitive impairment (5). Compared with MRI morphometry, which is most sensitive in detecting and monitoring hippocampal atrophy and closely related to performance in memory tasks (6), 18 F-FDG PET is more sensitive in detecting neuronal dysfunction in neocortical association areas. The function of these areas is primarily related to cognitive deficits in nonmemory domains such as language and orientation (7), which are of particular interest at the stage of transition from a relatively pure memory deficit in MCI to a more extensive cognitive impairment that characterizes dementia.…”

Imaging Biomarkers in Alzheimer's Disease

“…The power of imaging to enable earlier detection of disease is particularly important in the world of clinical research; it opens a window of opportunity for conducting research on the early phase of disease and for allowing earlier intervention. Imaging measures are also attractive putative markers of disease progression for clinical trials, although they are still far from acting as surrogate outcomes in AD and are likely to require multiple results from disease‐modifying trials in order for this to occur 18 . However, the need for reliable biomarkers for clinical trials in AD is clearly pressing.…”

“…Typical protocols for MRI safety scans include a fluid‐attenuated inversion recovery (FLAIR) sequence, sensitive to vasogenic edema, inflammation, and infarction and susceptibility‐weighted imaging to detect microbleeds. Diffusion imaging is sometimes incorporated, however, there is currently a lack of consensus guidelines as use of these markers is still somewhat in its infancy 18 …”

Biomarkers in Alzheimer's Disease

“…If a treatment could completely stop disease progression, then atrophy should slow to normal aging rates: approximately 1–2% per year in normal subjects aged between 70–80 years, in contrast with 4–6% per year in AD for hippocampal atrophy 13 and 0.5% per year in normal subjects aged around 70 years, in contrast with 2% per year in AD for whole brain atrophy 14 . Although a beneficial effect on clinical outcomes remains paramount, MRI markers of disease progression might provide evidence of disease slowing earlier or more cost‐effectively than clinical outcomes 15 . Such markers of disease severity and progression may be highly nonspecific (not relate to pathological progress) and yet still retain utility 1 .…”