Mild Cognitive Impairment

Transcription

1 Mild Cognitive Impairment Susan K. Schultz MD Professor of Psychiatry University of Iowa Carver College of Medicine Disclosure Statement I, Susan K. Schultz, MD do not have any financial interests or relationships with any manufacturers of products or providers of services I might be discussing in my presentation. I have no financial relationships with any of the companies supporting this educational event. I will not discuss any pharmaceuticals, medical procedures, or devices that are investigational or unapproved for use by the FDA. Diagnosis of Mild Cognitive Impairment (MCI) Mild Cognitive Impairment In population-based studies ranges from 10 to 20% in persons older than 65 years of age In general population about 1-2% may be diagnosed with dementia in one year In MCI: 5-10% in general community develop dementia each year MCI in specialty clinics: 10-15% per year Petersen RC, Smith GE, Waring SC et al. (1999), Arch Neurol 56(3): Peterson RC, N Engl J Med Jun 9;364(23): Importance of Managing MCI Record numbers of patients presenting with MCI Clinical Assessment An opportunity to delay or prevent onset of dementia Future trials may benefit patients without dementia who have Alzheimer s disease pathology Senile plaques and neurofibrillary tangles Volume loss in brain in the temporal lobe reflecting loss of neuron number May predate cognitive deficits Mild Neurocognitive Disorder Mild Neurocognitive Disorder New disorder Allows a diagnosis of mild symptoms May be associated with many different types of brain changes, not necessarily AD and not necessarily involving memory changes New in DSM-5 Diagnostic and Statistical Manual of Mental Disorders DSM5, American Psychiatric Press, Arlington

2 Features of Mild Neurocognitive Disorder (Mild NCD) Requires a concern about cognition Evidence that performance is below expectations for age and education Daily activities are not markedly impaired Mild NCD May Be Attributed to Different Conditions Alzheimer s disease Cerebrovascular disease (stroke) Frontotemporal lobar degeneration Parkinson s disease Diffuse Lewy Body disease Different Types of Cognitive Changes May Be Seen in Mild NCD Attention and Speed of Processing Tasks may feel more difficult to do More double-checking of work Trouble multi-tasking Executive Function More difficult to make decisions, organize complex activities, social events Different Types of Cognitive Changes May Be Seen in Mild NCD Visuospatial skills Trouble getting turned around and difficulty navigating places Difficulty searching for items on a written page or items in surroundings Other Types of Cognitive Changes in Mild NCD Memory Difficulty remembering recent events but usually can remember when reminders are used Need to use reminders and calendars more frequently Trouble remembering a list of items More Types of Cognitive Changes Language Trouble finding the correct words, using unusual words Social cognition Making inappropriate decisions 2

3 Criteria for Mild NCD A. Evidence of modest cognitive decline from a previous level of performance in one or more domains, based on: Concerns of the individual, a knowledgeable informant, or the clinician that there has been a mild decline in cognitive function A modest impairment in cognitive ability preferably documented by an objective clinical assessment Criteria for Mild NCD, continued Changes are NOT sufficient to interfere with independence in everyday activities However, greater effort, compensatory strategies, or accommodation may be required to maintain independence. The cognitive deficits do not occur exclusively in the context of a delirium. The cognitive deficits are not attributable to another disorder (e.g., major depressive disorder). Mild NCD Due to Alzheimer s Probable AD is diagnosed if one of the following is present Evidence of a causative Alzheimer s disease from either genetic testing or family history Mild NCD Due to Alzheimer s Possible AD may diagnosed: All three of the following are present: Clear evidence of decline in memory Steadily progressive, gradual decline in cognition, with no extended plateaus No evidence of mixed source (i.e., absence of concomitant cerebrovascular disease, Lewy Body disease, Parkinson s disease, etc.). Mild NCD Due to AD At the Mild Neurocognitive Disorder phase, Alzheimer s disease presents typically with impairment in memory, sometimes accompanied by deficits in executive function (e.g., difficulty making decisions, organizing complex activities, etc.) The clinical features are consistent with a vascular source: The onset of the cognitive deficits is temporally related to one or more vascular events Evidence for decline is prominent in complex attention (e.g., speed of processing information, multi-tasking difficulties) and/or executive function 3

4 There is evidence for the presence of cerebrovascular disease from history, physical examination and/or neuroimaging Vascular etiology may range from large vessel stroke to microvascular disease (small vessel ischemic disease, white matter ischemia) The symptoms are not better accounted for by another brain disease or systemic disorder Vascular Neurocognitive Disorder is considered Probable if one of the following is present: Clinical criteria are supported by neuroimaging evidence of cerebrovascular disease (neuroimaging-supported) The neurocognitive syndrome is temporally related to one or more cerebrovascular events and there is documented evidence of these events Possible if the clinical criteria are met, but neuroimaging is not available, and the onset of the cognitive deficits cannot be definitely related to one or more cerebrovascular events. Cerebrovascular disease and Alzheimer s disease may co-occur as causes of a neurocognitive disorder, in which case both etiologies should be recognized: Neurocognitive disorder due to cerebrovascular disease and Alzheimer s disease; or Neurocognitive disorder due to Alzheimer s disease and cerebrovascular disease. Vascular neurocognitive disorder and depression may co-occur. MCI and Depression Major Depressive Disorder in MCI Dementia Is depression a risk factor? Is it is the earliest sign of MCI? (-) MDD (+) MDD Followed 114 patients with amnestic MCI for 3 years 41 with MDD 73 without MDD 85% with (+) MDD developed incident AD vs. 32% with (-) MDD RR 2.6 (95% CI ) Modrego PJ et al. Arch Neurol 2004;61:

5 Depression and Progression of MCI to Dementia Followed 114 patients with amnestic MCI for 3 years 41 with MDD 73 without MDD 85% with (+) MDD developed incident AD vs. 32% with (-) MDD RR 2.6 (95% CI ) Treatment of Depression and MCI N=109 subjects >65 years in an outpatient geriatric mental health clinic 38% were diagnosed with MCI Despite adequate depression treatment response, nearly half of remitted depressed subjects still had a cognitive disorder Bhalla RK. Am J. Geriatr Psychiatry Apr;17(4): Modrego PJ et al. Arch Neurol 2004;61: Evaluation for MCI Patients/families frequently extremely anxious Among the most worried well patients Often the patient had parent with dementia Affected individuals may lack insight Meet patient and family separately if possible Patient alone for history and exam Family alone for history Often need to discuss highly charged issues Elements of the Evaluation History from patient and family Examination Diagnostic tests Screening cognitive assessment Montreal Cognitive Assessment MOCA < 26 Full neuropsychological testing Brain Imaging (CT, MRI, PET) Laboratory evaluation History of Present Illness Identify highest level of functioning, SES Anchor around when last well Earliest signs and symptoms Temporal course of symptoms Relationship to one another Systematic ROS Cognitive, functional, neuropsychiatric Role of Imaging Identify treatable/reversible conditions Mass lesions tumors, subdural hematoma Normal pressure hydrocephalus Establish other diagnoses Identify infarcts multi-infarct dementia, vascular dementia + AD Identify microvascular disease Better disease characterization Atypical presentations Early onset cases 5

6 Office Treatment: What does the evidence say? No clearly positive trials of AD medications Interventions with positive-leaning results Treatment of depression Exercise Cognitive stimulation Variety in leisure activities Cholinesterase Inhibitors Recommendations Not routinely indicated in MCI Three published and five unpublished randomized trials met the inclusion criteria (donepezil -3, rivastigmine-2, galantamine -3). Rate of conversion ranged 13% (over 2 yr) to 25% (over 3 yr) among treated patients 18% (over 2 y) to 28% (over 3 y) among those in the placebo groups Use in MCI was not associated with delay in the onset of AD / dementia Raschetti R et al. PLoS Med Nov 27;4(11):e338. Cholinesterase Inhibitors Patients with MCI and mild AD who were treated with cholinesterase inhibitors and memantine were assessed across ADNI sites. 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-ad were treated with ChEIs Those with MCI receiving ChEIs (with or without memantine) were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Schneider LS Arch Neurol Jan;68(1): Cholinesterase Inhibitors Older adults treated for depression: N=135; >65 yrs Compared donepezil with antidepressant therapy to placebo with antidepressant therapy In cognitively intact patients, donepezil appeared to have no benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression. The mild cognitive impairment subgroup (n=57) had recurrence rates of major depression of 44% with donepezil vs 12% with placebo Reynolds CF, Arch Gen Psychiatry Jan;68(1): Diet, Lifestyle, Nutrition Vitamin E There was no significant difference in progression from MCI to AD between the Vitamin E group and placebo. No significant difference between the placebo group and the Vitamin E group in death, adverse events. Issac MG: Cochrane Database Syst Rev Jul 16; 3. Farina N et al. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst Rev Nov 14. Risk factors and preventive interventions for AD : Diabetes mellitus, hyperlipidemia in midlife, and current tobacco use were associated with increased risk of AD Mediterranean-type diet, folic acid intake, low or moderate alcohol intake, cognitive activities, and physical activity were associated with decreased risk Daviglus ML et al. Arch Neurol Sep;68(9): Lifestyle Changes Manage co-morbidities and vascular factors Exercise Cognitive stimulation (?) Increase variety of leisure activities (?) Optimize nutrition Favor dietary choices with omega-3 fatty acids, antioxidants, polyphenols 6

7 Exercise Physical exercise, aging, and mild cognitive impairment: a population-based study. N=1324 without dementia who completed a Physical Exercise Questionnaire. 198 with MCI, 1126 without MCI Odds ratio: Any frequency of moderate exercise: 0.61 for midlife (age range, years) 0.68 for late life >65 years Conclusion: Any frequency of moderate exercise performed in midlife or late life was associated with a reduced odds of having MCI. Geda YE, Arch Neurol Jan;67(1):80-6. How Much to Exercise? Light exercise: e.g., bowling, leisurely walking, stretching, slow dancing, golfing with golf cart. Moderate exercise: e.g., brisk walking, hiking, aerobics, strength training, swimming, tennis doubles, yoga, martial arts, weight lifting, golfing without a golf cart, and moderate use of exercise machines (e.g., an exercise bike). Vigorous exercise: e.g., jogging, backpacking, bicycling uphill, tennis singles, racquetball, skiing, and intense use of exercise machines. Geda YE, Arch Neurol Jan;67(1):80-6. Meta-analysis of Exercise 15 studies; N= 33,816 non-demented subjects followed for 1-12 years 3210 had cognitive decline High level of physical activity HR 0.62 p< Low to moderate physical activity HR 0.65 p< Conclusion: A significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline. Sofi F et al. J Intern Med Jan;269(1): Summary MCI and Mild NCD offer ways to identify and follow early cognitive changes Prevention and treatment options are less well-defined and will be more clear as we continue to study our aging population. Use of medications depends on style of practice Treatment of depression Supportive care and management Lifestyle changes 7