APOE-4 Genotype and Neurophysiological Vulnerability to Alzheimer's and Cognitive Aging

Susan Bookheimer, Alison Burggren
2009 Annual Review of Clinical Psychology  
Many years before receiving a clinical diagnosis of Alzheimer's disease (AD), patients experience evidence of cognitive decline. Recent studies using a variety of brain imaging technologies have detected subtle changes in brain structure and function in normal adults with a genetic risk for AD; these brain changes have similar pathological features as AD, and some appear to be predictive of future cognitive decline. This review examines the most recent data on brain changes in genetic risk for
more » ... D and discusses the benefits and potential risks of detecting individuals at risk. Keywords neuroimaging; functional MRI (fMRI); dementia Alzheimer's disease (AD) is the most common form of dementia, affecting between 5% and 10% of individuals in their sixties; the incidence increases to nearly 50% of those who reach their nineties (Small et al. 1997) . Characterized first by memory loss, the disease is relentlessly progressive, culminating in sharp cognitive decline and complete incapacity. Because the brain but not the body is affected, patients can live for years while lacking the ability to recognize friends, family, and self, unable to communicate, eat independently, or maintain continence. Alzheimer's likewise has a devastating effect on families and caregivers (Schulz et al. 2008) ; up to 65% of caregivers suffer from depression (Papastavrou et al. 2007 ). Psychiatric symptoms, ranging from anxiety, agitation, and depression to psychosis, may occur in preclinical Alzheimer's mild cognitive impairment (MCI) at a rate of twice that of healthy controls (Geda et al. 2008 ). There is no cure for AD, and treatments are generally limited. A few pharmacotherapies may improve cognition for a relatively short duration, and although new treatments are under development, the most promising treatments aim to reduce or halt the rate of decline rather than reverse it. As these treatments are developed, there will be an increasing need to identify in the earliest possible stages the individuals fated to develop AD who will benefit most from intervention; preservation of cognitive status at the time of diagnosis offers little to patients or family.
doi:10.1146/annurev.clinpsy.032408.153625 pmid:19327032 pmcid:PMC3118550 fatcat:y6rar2w4cne45pzhnndx3nl2dy