SAN DIEGO – Robust behavioral changes are not common in presymptomatic familial Alzheimer’s disease, but increases in certain behaviors such as agitation, apathy, and appetitive changes can accompany early cognitive changes, results from a large ongoing study demonstrated.
The findings "are consistent with observations in late-onset Alzheimer’s disease and support behavioral changes in familial Alzheimer’s disease being a state associated with incipient Alzheimer’s pathology rather than a life-long disposition," Dr. John M. Ringman said at the annual meeting of the American Academy of Neurology.
"It’s well established now that the neuropathology of Alzheimer’s disease begins 15-20 years prior to overt symptoms," said Dr. Ringman, a neurologist at the Mary S. Easton Center for Alzheimer’s Disease Research at the University of California, Los Angeles. "Symptoms of depression, anxiety, apathy, and irritability are more frequent in persons with mild cognitive impairment (MCI). Further studies suggest that the presence of such symptoms in the context of MCI may better predict who will progress to develop Alzheimer’s disease."
Previous data published by Dr. Ringman and his associates suggest an increased degree of depressive symptoms in otherwise asymptomatic women inheriting PSEN1 mutations relative to their non–mutation carrying kin (J. Neurol. Neurosurg. Psychiatry 2004; 75:500-2). A study of persons destined to develop familial Alzheimer’s disease (FAD) "can help us differentiate between such symptoms as a ‘trait’ associated with a predisposition to AD or a ‘state’ related to the incipient development of AD pathology," he said.
At the meeting, Dr. Ringman presented findings from the first 212 men and women enrolled in the Dominantly Inherited Alzheimer Network (DIAN), an international multicenter study intended to characterize early clinical and biomarker changes occurring in people who inherit known FAD mutations in the PSEN1, APP, or PSEN2 genes. Men and woman at 50% risk for inheriting such a mutation underwent comprehensive evaluations including the Neuropsychiatric Inventory-Q (NPI-Q), the 15-item Geriatric Depression Scale (GDS), and the Clinical Dementia Rating Scale (CDR). Subjects who were aware of their mutation status were excluded from analysis.
The investigators classified FAD mutation carriers as being asymptomatic (defined as a CDR score of 0), mildly symptomatic (defined as a CDR score of 0.5), or overtly symptomatic (defined as a CDR score of greater than 0.5).* The researchers then compared FAD mutation carriers to noncarriers with respect to the frequency of behavioral changes on the NPI-Q and depression severity on the GDS. The 212 study participants included 133 mutation carriers and 79 noncarriers.
Of the 212 subjects, Dr. Ringman reported that 159 were at risk for PSEN1 mutations, 19 for PSEN2 mutations, and 34 for APP mutations. The 133 mutation carriers included 75 who were asymptomatic, 37 with mild symptoms, and 21 who were overtly affected. The researchers observed no statistically significant differences between asymptomatic mutation carriers and noncarriers in terms of neuropsychiatric symptoms. However, compared with noncarriers, mutation carriers with CDR scores of 0.5 demonstrated a significantly higher frequency of agitation (30% vs. 4%, respectively), apathy (41% vs. 3%), appetitive changes (30% vs. 9%), depressive symptoms (49% vs. 15%), disinhibition (16% vs. 1%), irritability (51% vs. 10%), and sleep changes (32% vs. 4%). In addition, the mean GDS score was mildly elevated in mildly symptomatic mutation carriers, compared with noncarriers (3.7 vs. 1.1; P value less than .001).
The study was funded by the National Institute on Aging, the Easton Consortium for Alzheimer’s Disease Drug Discovery and Biomarker Development, and UCLA’s Alzheimer’s Disease Research Center and Clinical Translational Research Institute. Dr. Ringman reported having no financial disclosures relevant to the study.
* 4/3/13, Correction to CDR score definitions.