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Objective: Depression and cognitive impairment are often comorbid in older adults, but optimal treatment strategies remain unclear. In a two-site study, the efficacy and safety of add-on donepezil versus placebo were compared in depressed patients with cognitive impairment receiving stable antidepressant treatment.Methods: A randomized, double-blind, placebo-controlled trial was conducted in older adults with depression and cognitive impairment (https://clinicaltrials.gov/ct2/show/NCT01658228; NCT01658228). Patients received open-label antidepressant treatment for 16 weeks, initially with citalopram and then with venlafaxine, if needed, followed by random assignment to add-on donepezil 5-10 mg daily or placebo for another 62 weeks. Outcome measures were neuropsychological test performance (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog] and Selective Reminding Test [SRT] total immediate recall) and instrumental activities of daily living (Functional Activities Questionnaire).Results: Of 81 patients who signed informed consent, 79 patients completed the baseline evaluation. Open antidepressant treatment was associated with improvement in depression in 63.93% responders by week 16. In the randomized trial, there were no treatment group differences between donepezil and placebo on dementia conversion rates, ADAS-Cog, SRT total immediate recall, or FAQ. Neither baseline cognitive impairment severity nor apolipoprotein E e4 genotype influenced donepezil efficacy. Donepezil was associated with more adverse effects than placebo.Conclusion: The results do not support adjunctive off-label cholinesterase inhibitor treatment in patients with depression and cognitive impairment. The findings highlight the need to prioritize discovery of novel treatments for this highly prevalent population with comorbid illnesses. [ABSTRACT FROM AUTHOR]

Jennifer Gatchel (Symposium Co-chair) will introduce the speakers and then present data from the Harvard Aging Brain Study and screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study. Mood, cognition, and PET data from 4,486 participants will be presented from the A4 Study and from 135 participants from the Harvard Aging Brain Study. These unpublished data show associations among neuropsychiatric symptoms, cognition, and in vivo neuroimaging biomarkers—amyloid and tau—in cognitively unimpaired individuals. Findings support cortical amyloid and regional cerebral tau as risk factors for cognitive decline in older adults. Davangere Devanand will review the evidence that olfactory identification deficits predict the development of Alzheimer's dementia, and show that olfactory impairments are superior to episodic verbal memory deficits in predicting cognitive decline. He will present data from a large community sample showing that intact performance on brief global cognitive and olfactory tests is associated with lack of transition to dementia during follow-up. These unique data will show that in 711 subjects, intact olfactory and cognitive abilities were protective with few transitions to dementia and none in the 70-75 and 81-83 years age groups. Terry Goldberg will review the apolipoprotein E e4 allele (APOE e4) as a risk factor for Alzheimer's dementia, and present unpublished data from the National Alzheimer's Consortium database showing that the apolipoprotein E e2 (APOE e2) genotype is protective against amyloid and tau pathologies of Alzheimer's disease but not Lewy body pathology, fronto-temporal or related tauopathy dementias as identified by gold standard neuropathological diagnosis. He will describe unpublished genetic and pathologic results from the Alzheimer's NACC consortium (N=1557) showing that APOE e2 protects against Alzheimer's and APOE e4 promotes Lewy body pathology in limbic and cortical regions but not midbrain. Gary Small (Symposium Chair) will moderate the audience questions and panel responses after presenting new data from randomized controlled trials indicating the cognitive benefits of pomegranate juice, bioavailable curcumin, or physical exercise – all strategies that reduce inflammation. These findings, as well as previous research on medications, physical activity, diet, obesity, and other risk/protective factors, suggest that several anti-inflammatory interventions may protect brain health and lower the risk for Alzheimer's dementia. He will describe data from placebo-controlled trials of memory effects of pomegranate juice (N=260) and curcumin (N=40), and a trial of memory training/aerobic exercise (N=55). [ABSTRACT FROM AUTHOR]

Jennifer Gatchel (Symposium Co-chair) will introduce the speakers and then present data from the Harvard Aging Brain Study and screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study. Mood, cognition, and PET data from 4,486 participants will be presented from the A4 Study and from 135 participants from the Harvard Aging Brain Study. These unpublished data show associations among neuropsychiatric symptoms, cognition, and in vivo neuroimaging biomarkers—amyloid and tau—in cognitively unimpaired individuals. Findings support cortical amyloid and regional cerebral tau as risk factors for cognitive decline in older adults. Davangere Devanand will review the evidence that olfactory identification deficits predict the development of Alzheimer's dementia, and show that olfactory impairments are superior to episodic verbal memory deficits in predicting cognitive decline. He will present data from a large community sample showing that intact performance on brief global cognitive and olfactory tests is associated with lack of transition to dementia during follow-up. These unique data will show that in 711 subjects, intact olfactory and cognitive abilities were protective with few transitions to dementia and none in the 70-75 and 81-83 years age groups. Terry Goldberg will review the apolipoprotein E e4 allele (APOE e4) as a risk factor for Alzheimer's dementia, and present unpublished data from the National Alzheimer's Consortium database showing that the apolipoprotein E e2 (APOE e2) genotype is protective against amyloid and tau pathologies of Alzheimer's disease but not Lewy body pathology, fronto-temporal or related tauopathy dementias as identified by gold standard neuropathological diagnosis. He will describe unpublished genetic and pathologic results from the Alzheimer's NACC consortium (N=1557) showing that APOE e2 protects against Alzheimer's and APOE e4 promotes Lewy body pathology in limbic and cortical regions but not midbrain. Gary Small (Symposium Chair) will moderate the audience questions and panel responses after presenting new data from randomized controlled trials indicating the cognitive benefits of pomegranate juice, bioavailable curcumin, or physical exercise – all strategies that reduce inflammation. These findings, as well as previous research on medications, physical activity, diet, obesity, and other risk/protective factors, suggest that several anti-inflammatory interventions may protect brain health and lower the risk for Alzheimer's dementia. He will describe data from placebo-controlled trials of memory effects of pomegranate juice (N=260) and curcumin (N=40), and a trial of memory training/aerobic exercise (N=55). [ABSTRACT FROM AUTHOR]

The article identifies psychological and physiological factors which antedate dementia and demise among the elderly focusing on its effects on different states of predementia, studies on cognitive impairment, and research on brain aging and dementia.