BOSTON—Temporoparietal cortical thickness may identify patients with early-onset or atypical dementia more effectively than hippocampal volume, according to research presented at the 2013 Alzheimer’s Association International Conference.
In a cross-sectional analysis, measurements of hippocampal volume identified 35% of patients with early-onset or atypical dementia, and measurements of temporoparietal cortical thickness identified 92% of the patients. The findings have the potential to change the way in which atypical patients are diagnosed, thus speeding the process considerably, said Gil D. Rabinovici, MD.
“These patients are typically young and can face a long road toward getting an accurate diagnosis,” one that may take several years, said Dr. Rabinovici, Assistant Professor of Neurology in Residence at the University of California, San Francisco (UCSF). “Getting a good, clear answer early on is key to getting [patients] the support they need, including therapy for symptoms, as well as time to plan and get on disability.”
Identifying Early-Onset and Atypical Dementia
Dr. Rabinovici and colleagues evaluated hippocampal volume and cortical atrophy in a cohort of patients with typical and atypical dementias. The group consisted of 49 patients examined at the UCSF Memory and Aging Center. Fourteen patients had early-onset dementia, 18 had primary progressive aphasia, and 17 had posterior cortical atrophy. These patients were compared with a cohort of seven patients with late-onset Alzheimer’s dementia, 97 subjects with confirmed Alzheimer’s disease from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and 166 ADNI normal controls.
The mean age of the late-onset group was 78, compared with 59 for the early-onset patients and 63 for those in the atypical-onset group. Mean age was 75 for the ADNI controls and 76 for the ADNI Alzheimer’s patients.
A receiver operating characteristic analysis showed that hippocampal volume identified late-onset Alzheimer’s patients with 86% sensitivity. But this measurement was significantly less sensitive in the early-onset group (43%), in individuals with primary progressive aphasia (28%), and in subjects with posterior cortical atrophy (35%).
Temporoparietal cortical thickness was a significantly more accurate method of identifying patients with atypical dementia. The technique had 93% sensitivity for early-onset dementia, 100% sensitivity for primary progressive aphasia, and 82% sensitivity for posterior cortical atrophy. Overall, the measurement had a 92% sensitivity for identifying patients with atypical dementia.
Clinical Variables Can Make Diagnosis Difficult
Early-onset or atypical dementia can be difficult to diagnose because patients often present with unusual symptoms. Instead of mentioning memory problems, they tend to complain of language and visuospatial dysfunction and problems with executive function, decision making, and judgment. “Memory can be spared in this population,” said Dr. Rabinovici. “There is usually no complaint of depression because they don’t recognize the symptoms.” Initial referrals, often to an ophthalmologist or psychiatrist, are usually unhelpful, he added.
Early-onset or atypical Alzheimer’s disease and frontotemporal dementia share a considerable number of symptoms, and this situation contributes to a delayed diagnosis of both conditions. “Studies show that even experts have a tough time discriminating between the two” based solely on clinical presentation, said Dr. Rabinovici.
The recent inclusion of beta-amyloid brain imaging into the Alzheimer’s diagnostic criteria might help clarify the picture, he said. However, amyloid imaging agents are not widely available and, because of the recent federal decision not to cover such exams, probably will not be available anytime soon.
“The other option is to use imaging markers of neuronal injury that would show brain atrophy, like MRI,” said Dr. Rabinovici. “It’s much more accessible for most people.” But most quantitative imaging studies focus on hippocampal volume because of its relation to memory. “This is a powerful marker in older patients, but in younger patients, there seems to be a sparing of the hippocampus for reasons we don’t entirely understand. They seem to show more atrophy in brain areas involved with vision and language, which makes sense, given their symptoms,” said Dr. Rabinovici.
Measuring Temporoparietal Cortical Thickness Could Reduce Expenses
The findings could have profound implications for clinical care. “Structural imaging of some sort is already part of the standard protocol for evaluating people with cognitive complaints, but few centers actually measure this kind of atrophy,” said Dr. Rabinivici. “In the typical scenario, the radiologist uses the scan to rule out strokes and tumors, but there’s no comment on atrophy. This is something that’s missing, even at really good centers.”
Quantitative measures like temporoparietal cortical thickness could prove useful for these patients, “particularly in light of the environment around amyloid imaging right now,” he added. “The information is already available in the MRI scan, and interpreting it correctly not only won’t break the bank, it will spare much expense in the prolonged search for a diagnosis that so many of these patients endure.”