Dementia update 2005

As noted, this update necessarily reflects the views of the author and cannot be assumed to be either all encompassing or balanced. With these caveats, important current themes in dementia research include the following: AD is highly prevalent in older adults yet remains underdiagnosed. The strongest risk factors for sporadic AD are age, family history, and APOE genotype. Many other modulating factors may operate at distinct "windows" or timepoints during a long preclinical phase of AD to increase or decrease risk for the clinically expressed disorder. Examples include cardiovascular factors in midlife (increased risk for AD) and engagement in cognitive, physical, and social activities (decreased risk for AD). There is no conclusive evidence of reduced risk for AD for statins, nonsteroidal anti-inflammatory drugs, or the antioxidant vitamins E and C. Estrogen replacement therapy does not reduce risk for AD, at least in women 65 years and older, and may be harmful. AD can be diagnosed with high accuracy using clinical methods that combine informant interviews and objective assessment of the patient. The rate of cognitive decline in AD is determined largely by the severity of dementia. The PDA-approved symptomatic therapies for AD are the cholinesterase inhibitor drugs for mild-moderate AD and memantine for moderate-severe AD. The cost-effectiveness of cholinesterase inhibitor therapy in AD has been questioned. The safety of high-dose vitamin E supplementation and the atypical antipsychotic drugs have been challenged. Multiple candidate biomarkers for AD are being investigated, but to date none have been validated. CMS has approved reimbursement of PET studies as an adjunct tool for dementia evaluation in limited circumstances that involve the distinction of frontotemporal lobar degeneration and AD. Neuroimaging measures potentially can be used as surrogate markers for AD. In particular, the advent of amyloid tracers holds promise for molecular imaging as a diagnostic and prognostic tool in AD. Agents with the potential to modify the AD process currently are in trial or soon will be, including immunotherapeutic strategies using passive administration of anti-Aβ monoclonal antibodies. The preclinical stage of AD will require detection by antecedent biomarkers but may be the optimal period for intervention should safe, tolerable, and effective agents be developed to delay or prevent the onset of dementia. MCI criteria have been expanded to include prodromal forms of non-AD dementing disorders. Not all individuals with MCI will progress to dementia. However, the subset of MCI individuals with prodromal AD can be identified by clinical methods and for these individuals MCI may represent the earliest symptomatic stage of AD. There is no currently approved treatment of the indication of MCI. Pure vascular dementia is rare (at least in the United States). Attention increasingly is focused on understanding how vascular insults, including microvascular pathology, contribute to cognitive impairment in "mixed dementia." Dementia with Lewy Bodies is the second most common dementing disorder after AD. However, its clinical diagnosis is problematic. Frontotemporal lobar degeneration encompasses a group of heterogeneous clinical and neuropathological phenotypes. Motor neuron disease and frontotemporal lobar degeneration frequently co-occur. 20. Neuroimaging findings in combination with cerebrospinal assays are useful in the diagnostic assessment of cases of suspected Creutzfeldt-Jakob disease.