Mony J. de Leon

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism.

Having a parent affected with late-onset Alzheimers disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Forty-nine 50- to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[18F]fluoro-2-deoxy-d-glucose–positron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH−). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH− and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH− subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.

Magnetic resonance and PET studies in the early diagnosis of Alzheimer’s disease

The demographics of aging identify an immediate need for the early diagnosis and development of dementia prevention strategies. Recent neuropathological studies have pointed to the early involvement of the hippocampus and entorhinal cortex in the progression of Alzheimer’s disease in the brain. In particular, these studies have implicated tau-related pathology as an important cause of neuronal death. In addition, there is a large body of evidence showing that β-amyloid, which has a predilection for the neocortex, is also involved early in the course of the disease and may also have toxic effects on cells. In vivo cerebrospinal fluid studies have shown that markers for these brain changes have a diagnostic value for Alzheimer’s disease and that some measures also provide diagnostic specificity for Alzheimer’s disease. Structural and metabolic imaging studies demonstrate brain changes in impaired and at-risk individuals. While currently available magnetic resonance and positron emission tomography techniques are not by themselves specific for the pathologic features of Alzheimer’s disease, there are patterns of change that have been useful for the early diagnosis. As such, both prediction and longitudinal imaging studies demonstrate a capacity to recognize abnormalities that relate to future Alzheimer’s disease and most recently to future mild cognitive impairment. This review highlights cross-sectional, prediction, and longitudinal magnetic resonance and positron emission tomography imaging studies and attempts to put into perspective their utility for the early diagnosis of Alzheimer’s disease, and for their utility to provide diagnostic specificity. It is concluded that there is considerable promise for an early and specific diagnosis for Alzheimer’s disease by combining information from imaging and biomarker modalities.

Framigham cardiovascular risk profile correlates with impaired hippocampal and cortical perfusion

Lidia Glodzik, Henry Rusinek, Miroslaw Brys, Wai Tsui, Elizabeth Pirraglia, Lisa Mosconi, Susan De Santi, Yi Li, Mony de Leon, Center for Brain Health, Center of Excellence on Brain Aging, NYUSM, New York, NY, USA; Department of Radiology, NYUSM, New York, NY, USA; NYU Langone Medical Center, New York, NY, USA; MedAvante Inc., Hamilton, NJ, USA; Nathan Kline Institute, Orangeburg, NY, USA. Contact e-mail: lidia.glodzik@nyumc.org