Incidence of dementia among participants and nonparticipants in a longitudinal study of cognitive aging.

Although rates of incident dementia have been reported from several populations, the impact of nonparticipation on dementia incidence in studies of cognitive aging is unknown. In 2004, investigators with the Mayo Clinic Study of Aging selected persons aged 70-89 years from an enumeration of all Olmsted County, Minnesota, residents (age- and sex-stratified random sample). Of 4,398 potential participants, 2,050 agreed to undergo an in-person health assessment. Those participants were reevaluated in person using standard diagnostic procedures approximately every 15 months over a median follow-up period of 5.7 years (through September 15, 2013). There were 1,679 persons who refused any participation. A trained nurse abstractor reviewed the medical records of nonparticipants using the Rochester Epidemiology Project's medical record linkage system a median of 3.9 years after refusal. Nonparticipants had a higher prevalence of dementia than participants evaluated in person (6.5% vs. 3.3%; P < 0.0001). The standardized incidence of dementia was not significantly higher among the nonparticipants (23.2 per 1,000 person-years) than in those evaluated in person (19.6 per 1,000 person-years; hazard ratio = 1.17, 95% confidence interval: 0.95, 1.43 (P = 0.13); adjusted for education and sex, with age as the time scale). The small, nonsignificant impact of nonparticipation on rates of incident dementia is reassuring for future studies based on incident dementia cases.

Association of diabetes with amnestic and nonamnestic mild cognitive impairment.

BACKGROUND: Type 2 diabetes may increase the risk of amnestic mild cognitive impairment (aMCI) through Alzheimer's disease (AD)-related and vascular pathology and may also increase the risk of nonamnestic MCI (naMCI) through vascular disease mechanisms. We examined the association of type 2 diabetes with mild cognitive impairment (MCI) and MCI subtype (aMCI and naMCI) overall and by sex. METHODS: Participants were Olmsted County, Minnesota residents (70 years and older) enrolled in a prospective, population-based study. At baseline and every 15 months thereafter, participants were evaluated using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing for a diagnosis of normal cognition, MCI, and dementia by a consensus panel. Type 2 diabetes was ascertained from the medical records of participants at baseline. RESULTS: Over a median 4.0 years of follow-up, 348 of 1450 subjects developed MCI. Type 2 diabetes was associated (hazard ratio [95% confidence interval]) with MCI (1.39 [1.08-1.79]), aMCI (1.58 [1.17-2.15]; multiple domain: 1.58 [1.01-2.47]; single domain: 1.49 [1.09-2.05]), and the hazard ratio for naMCI was elevated (1.37 [0.84-2.24]). Diabetes was strongly associated with multiple-domain aMCI in men (2.42 [1.31-4.48]) and an elevated risk of multiple domain naMCI in men (2.11 [0.70-6.33]), and with single domain naMCI in women (2.32 [1.04-5.20]). CONCLUSIONS: Diabetes was associated with an increased risk of MCI in elderly persons. The association of diabetes with MCI may vary with subtype, number of domains, and sex. Prevention and control of diabetes may reduce the risk of MCI and Alzheimer's disease.

Telemedicine barriers associated with regional quality measures.

Telemedicine practitioners are familiar with multiple barriers to delivering care at a distance. Licensing and reimbursement barriers are well known and are being addressed at national and state levels by the American Telemedicine Association. Another telemedicine barrier comes in the form of quality measures for diabetes. Minnesota medical practices are currently being compared on the proportion of their patients with diabetes who have attained goals for blood pressure, low-density lipoprotein cholesterol, and hemoglobin A1C. The quality measure for blood pressure specifically excludes measurements taken by the patient, thus precluding blood pressure telemonitoring as a way to meet the blood pressure goal. To counter this barrier, advocacy in telemedicine is needed so that telemonitoring as a data collection tool is included in quality measures.

Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study.

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is associated with neurodegenerative disease and particularly with the synucleinopathies. Convenience samples involving subjects with idiopathic RBD have suggested an increased risk of incident mild cognitive impairment (MCI), dementia (usually dementia with Lewy bodies), and Parkinson disease (PD). There are no data on such risks in a population-based sample. METHODS: Cognitively normal subjects aged 70 to 89 years in a population-based study of aging who screened positive for probable RBD using the Mayo Sleep Questionnaire were followed at 15-month intervals. In a Cox proportional hazards model, we measured the risk of developing MCI, dementia, and PD among the exposed (probable RBD [pRBD](+)) and unexposed (pRBD(-)) cohorts. RESULTS: Forty-four subjects with pRBD(+) status at enrollment (median duration of pRBD features was 7.5 years) and 607 pRBD(-) subjects were followed prospectively for a median of 3.8 years. Fourteen of the pRBD(+) subjects developed MCI, and 1 developed PD (15/44 = 34% developed MCI/PD); none developed dementia. After adjustment for age, sex, education, and medical comorbidity, pRBD(+) subjects were at increased risk of MCI/PD (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-3.9; p = 0.005). Inclusion of subjects who withdrew from the study produced similar results, as did exclusion of subjects with medication-associated RBD. Duration of pRBD symptoms did not predict the development of MCI/PD (HR, 1.05 per 10 years; 95% CI, 0.84-1.3; p = 0.68). INTERPRETATION: In this population-based cohort study, we observed that pRBD confers a 2.2-fold increased risk of developing MCI/PD over 4 years.

Differentiation of hydrochlorothiazide-induced dermatitis from stasis dermatitis.

A woman in her 60s with a history of hypertension and stasis dermatitis presented to a primary care clinic with a bilateral, erythematous rash on the legs, stomach, and chest. Photosensitive rash and dermatitis may be caused by many conditions. Hydrochlorothiazide-induced dermatitis is a rare side effect of thiazide diuretics. Early identification of sulfa-sensitivity and photoallergic or phototoxic reaction is essential to accurate diagnosis and treatment of photosensitive dermatitis. Soliciting a targeted history is essential to delineating drug-induced dermatitis from stasis dermatitis. A thorough skin examination can elucidate the focal or extensive nature of the rash and is essential to making an accurate diagnosis. Immediate cessation of hydrochlorothiazide and switching drugs classes for hypertension management typically leads to resolution of symptoms.

Engaging in cognitive activities, aging, and mild cognitive impairment: a population-based study.

The authors investigated whether engaging in cognitive activities is associated with aging and mild cognitive impairment (MCI) in a cross-sectional study derived from an ongoing population-based study of normal cognitive aging and MCI in Olmsted County, MN. A random sample of 1,321 study participants ages 70 to 89 (N=1,124 cognitively normal persons, and N=197 subjects with MCI) were interviewed about the frequency of cognitive activities carried out in late life (within 1 year of the date of interview). Computer activities; craft activities, such as knitting, quilting, etc.; playing games; and reading books were associated with decreased odds of having MCI. Social activities, such as traveling, were marginally significant. Even though the point-estimates for reading magazines, playing music, artistic activities, and group activities were associated with reduced odds of having MCI, none of these reached statistical significance. The equally high prevalence of reading newspapers in both groups yielded no significant between-group difference.

What is the quality of life in the oldest old?

BACKGROUND: Maintaining and improving quality of life has become a major focus in geriatric medicine, but the oldest old have received limited attention in clinical investigations. We aimed to investigate the relationship between self-perceived and caregiver-perceived quality of life (QOL), cognitive functioning, and depressive symptoms in the oldest old. METHODS: This IRB-approved prospective study recruited community dwellers aged 90-99 years old. Collected data included neurological evaluation, DSM III-R criteria for dementia, Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), Geriatric Depression Scale (GDS), Record of Independent Living (ROIL), and QOL assessment using the Linear Analogue Self Assessment (LASA). RESULTS: Data on 144 subjects (56 cognitively normal (normal), 13 mild cognitive impairment (MCI), 41 dementia (DEM), 34 dementia with stroke and parkinsonism (DEMSP)) over a three-year period were analyzed. Mean ages ranged from 93 to 94 years, and the majority were female with at least high school education. Overall functional ability was higher in groups without dementia (p < 0.0001). All subjects reported high overall QOL (range 6.76-8.3 out of 10), regardless of cognitive functioning. However, caregivers perceived the subjects' overall QOL to be lower with increasing severity of cognitive impairment (p < 0.0001). Lower GDS scores correlate with higher self-perceived overall QOL (ρ = -0.38, p < 0.0001). CONCLUSIONS: In our community sample of the oldest old, there was a fairly high level of overall QOL, whether or not cognitive impairment exists. Individuals perceive their QOL better than caregivers do, and the difference in subjects' and caregivers' perception is more pronounced for the groups with dementia. QOL is more strongly correlated with depressive symptoms than with dementia severity.

Metabolic syndrome, inflammation, and nonamnestic mild cognitive impairment in older persons: a population-based study.

The metabolic syndrome (MetS) is more strongly associated with cognitive impairment in the presence of inflammation. This suggests that the association of MetS with mild cognitive impairment (MCI) may vary with the etiology and the subtype of MCI. This study investigated the association between MetS with or without inflammation and MCI [amnestic (a-MCI) and nonamnestic (na-MCI)]. We studied a randomly selected sample of 1969 participants (ages 70 to 89 y) from Olmsted County, MN, using the Clinical Dementia Rating Scale, a neurologic evaluation, and neuropsychologic testing. Data for participants were reviewed for a diagnosis of normal cognition, MCI, or dementia. Clinical components of MetS were ascertained by interview and confirmed from the medical records; biochemical measurements were assayed from a blood draw. We compared 88 na-MCI cases and 241 a-MCI cases with 1640 cognitively normal participants. MetS was not associated with either na-MCI or a-MCI. High C-reactive protein (CRP; highest tertile vs lowest tertile) was associated with na-MCI [odds ratio (OR)=1.85; 95% confidence interval (CI)=1.05, 3.24] but not with a-MCI, after adjusting for sex, age, and years of education. The combination of MetS and high CRP (compared to no MetS and lowest CRP tertile) was associated with na-MCI (OR=2.31; 95% CI=1.07, 5.00), but not with a-MCI (OR=0.96; 95% CI=0.59, 1.54). The combined presence of MetS and high levels of inflammation is associated with na-MCI in this elderly cohort, and suggests etiologic differences in MCI subtypes.

Association of C-reactive protein with mild cognitive impairment.

BACKGROUND: Inflammation is proposed to play a role in the development of Alzheimer's disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population-based sample. METHODS: Olmsted County, MN, residents aged 70-89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis alpha (TNFalpha), and adiponectin were measured at baseline. RESULTS: Among 313 subjects with MCI and 1570 cognitively normal subjects, a CRP level in the upper quartile (>3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00-2.01) and with nonamnestic MCI (OR, 2.05; 95% CI, 1.12-3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (OR, 1.21; 95% CI, 0.81-1.82). No association was observed with the other inflammatory markers. CONCLUSIONS: Plasma CRP is associated with prevalent MCI and with nonamnestic MCI in elderly, nondemented persons in a population-based setting. These findings suggest the involvement of inflammation in the pathogenesis of MCI.

Nelfinavir monotherapy increases naïve T-cell numbers in HIV-negative healthy young adults.

Although patients treated with HIV protease inhibitor (PI) containing regimens manifest increases in naïve T cell number, it is unclear whether this is due to reduction in viral replication or a direct drug effect. We questioned whether Nelfinavir monotherapy directly impacted naïve T-cell number in HIV-negative individuals. HIV-negative volunteers received Nelfinavir, 1250 mg orally, BID for 3 weeks, and T-cell receptor recombination excision circles (TREC) content in peripheral blood were assessed. Whereas TREC copies did not change over 3 weeks in untreated controls, TREC copies/copies CCR5 increased following Nelfinavir monotherapy in 8 patients (p < 0.02), and did not change in 7 patients (p = NS). Those patients who responded were younger than those who did not with a median age of 55 years for responders and 71 years for non-responders (p < 0.03). The increase in TREC was most pronounced in those patients less than 40-years old (p < 0.01). Moreover, the patients who did not increase TREC levels were more likely to have suffered a medical illness previously shown to reduce thymic function. In HIV-negative patients, monotherapy with the HIV PI Nelfinavir for 21 days increases TREC-positive naïve T cell number, particularly in individuals who are healthy and young.

The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics.

BACKGROUND: The objective of this study was to establish a prospective population-based cohort to investigate the prevalence, incidence and risk factors for mild cognitive impairment (MCI) and dementia. METHODS: The Olmsted County, Minn., population, aged 70-89 years on October 1, 2004, was enumerated using the Rochester Epidemiology Project. Eligible subjects were randomly selected and invited to participate. Participants underwent a comprehensive in-person evaluation including the Clinical Dementia Rating Scale, a neurological evaluation and neuropsychological testing. A consensus diagnosis of normal cognition, MCI or dementia was made by a panel using previously published criteria. A subsample of subjects was studied via telephone interview. RESULTS: Four hundred and two subjects with dementia were identified from a detailed review of their medical records but were not contacted. At baseline, we successfully evaluated 703 women aged 70-79 years, 769 women aged 80-89 years, 730 men aged 70-79 years and 517 men aged 80-89 years (total n = 2,719). Among the participants, 2,050 subjects were evaluated in person and 669 via telephone. CONCLUSIONS: Strengths of the study are that the subjects were randomly selected from a defined population, the majority of the subjects were examined in person, and MCI was defined using published criteria. Here, we report the design and sampling, participation, baseline measures and sample characteristics.

Mild Cognitive Impairment in Geriatrics.

Mild cognitive impairment remains a clinical diagnosis, aided by history, neurologic examination, screening mental status examination, and secondary testing. It can be difficult to distinguish from normal aging without understanding a patient's prior level of intellectual function and new complaint. Geriatricians encounter patients with mild cognitive impairment in all long-term care settings. Making the diagnosis allows patients and their families to understand limits and develop strategies to maximize function. Etiologies associated with mild cognitive impairment include degenerative and vascular processes, psychiatric causes, and comorbid medical conditions. Treatable medical conditions may also present as mild cognitive impairment and have reversible outcomes.

Alzheimer's disease patients' cognitive status and course years prior to symptom recognition.

This is a prospective examination of the cognitive performance and cognitive course of persons in an asymptomatic "preclinical" phase who eventually developed Alzheimer's disease (AD). We compared performances on the Mayo Cognitive Factor Scales (MCFS) of 20 persons in a neurologically normal cohort who subsequently developed AD to the performances of 60 persons who remained free of dementia symptoms. For the AD patients, exams occurred prior to the appearance of dementia symptoms (an average of 4.2 and 1.5 years prior to symptom onset). Results reveal strong group differences on learning and retention, with eventual AD patients scoring lower than controls years prior to reporting symptoms of the disease. There was no significant interaction effect (group x testing session) for memory retention, suggesting that memory decline in this preclinical period may be too slow to be a useful indicator of future AD. A significant interaction (but no group effect) was seen for verbal comprehension.

De novo 2p16.1 microdeletion with metastatic esophageal adenocarcinoma.

Microdeletions involving chromosome 2p15-16.1 are a rare genetic abnormality and have been reported in 18 separate patients, mainly children, since 2007. This microdeletion syndrome is characterised by a heterogeneous expression of intellectual impairment, dysmorphic facies, musculoskeletal abnormalities and potential neurodevelopmental anomalies. We report the first case of natural progression in an adult patient who died at a young age of metastatic esophageal adenocarcinoma. Important learning points include the variable phenotypic expression of this microdeletion syndrome and the fact that clinicians must be thorough in investigating objective discrepancies in patients who cannot endorse classical symptoms.

Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia.

BACKGROUND: The pathologic outcome of patients diagnosed with mild cognitive impairment (MCI) following progression to dementia is poorly understood. OBJECTIVE: To determine the pathologic substrates of dementia in cases with prior diagnosis of amnestic MCI. DESIGN AND SETTING: Community-based cohort. PATIENTS: Thirty-four subjects followed up prospectively as part of a community-based study who were diagnosed with amnestic MCI, progressed to clinical dementia, and underwent subsequent postmortem brain analysis. MAIN OUTCOME MEASURES: Neuropathologic analyses resulted in assignment of a primary pathologic diagnosis and included staging of Alzheimer pathologic abnormalities and identification of contributing vascular disease, Lewy bodies, and argyrophilic grains. RESULTS: Although the majority of subjects progressed both clinically and pathologically to Alzheimer disease (AD), 10 (29%) of them developed non-AD primary pathologic abnormalities. All of the cases were found to have sufficient pathologic abnormalities in mesial temporal lobe structures to account for their amnestic symptoms regardless of the cause. Most subjects were found to have secondary contributing pathologic abnormalities in addition to primary pathologic diagnoses. No significant differences between subjects with and without neuropathologically proven AD were detected in demographic variables, apolipoprotein E genotype, or cognitive test measures at onset of MCI, onset of dementia, or last clinical evaluation. CONCLUSIONS: The neuropathologic outcome of amnestic MCI following progression to dementia is heterogeneous, and it includes AD at a high frequency. Complex neuropathologic findings including 2 or more distinct pathologic entities contributing to dementia may be common in community-based cohorts. Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD.

Neuropathologic features of amnestic mild cognitive impairment.

BACKGROUND: The neuropathologic substrate of amnestic mild cognitive impairment (aMCI) is not known. OBJECTIVE: To determine the neuropathologic features of patients who died while their clinical classification was aMCI. DESIGN: Cohort study. SETTING: Community based. PARTICIPANTS: Sixty-six individuals, including 15 who had memory impairment beyond that allowed for aging but who were not demented, were studied along with 28 clinically healthy individuals and 23 patients with probable Alzheimer disease (AD) for comparison. MAIN OUTCOME MEASURES: Standard neuropathologic techniques and classification according to Khachaturian, Consortium to Establish a Registry for Alzheimer Disease, and National Institute on Aging-Reagan criteria were used to analyze autopsy tissue from 15 individuals who died while their clinical diagnosis was aMCI. For comparison, autopsy data on age-matched groups of clinically healthy individuals and patients with probable AD were analyzed. RESULTS: Most patients with aMCI did not meet the neuropathologic criteria for AD, but their pathologic findings suggest a transitional state of evolving AD. All the patients with aMCI had pathologic findings involving medial temporal lobe structures, likely accounting for their memory impairment. In addition, there were many concomitant pathologic abnormalities, including argyrophilic grain disease, hippocampal sclerosis, and vascular lesions. CONCLUSIONS: The neuropathologic features of aMCI matched the clinical features and seemed to be intermediate between the neurofibrillary changes of aging and the pathologic features of very early AD.

Challenges in the Pharmacological Management of Nursing Home Residents with Overactive Bladder or Urinary Incontinence.

OBJECTIVES: To determine the proportion of nursing home (NH) residents (NHR) with overactive bladder (OAB) or urinary incontinence (UI) with potential pharmacodynamic contraindications to antimuscarinic treatment because of concomitant anticholinergic medications or acetylcholinesterase inhibitors (AChEIs) and nonpharmacological limitations to antimuscarinic treatment. DESIGN: Cross-sectional retrospective analysis. SETTING: U.S. skilled nursing facilities. PARTICIPANTS: Nursing home residents with a diagnosis of OAB or UI. MEASUREMENTS: Linked and deidentified pharmacy claims and Minimum Data Set (MDS) 3.0 records (October 1, 2010 to September 30, 2012). RESULTS: Of NHRs, 71.3% received at least one anticholinergic medication. Medications that can cause or worsen UI were used commonly. AChEIs and antimuscarinic treatment were prescribed concurrently in 24% of NHRs with OAB or UI. NHRs with OAB or UI were more likely to have concurrent moderate to severe cognitive impairment (MSCI) (70.1%) than those without (29.9%) (P < .001). NHRs with or without OAB or UI and with MSCI were more likely to be treated with an anticholinergic medication than those without MSCI (P = .001). When NHRs with MSCI, severe mobility impairment (SMI), and anticholinergic medication and AChEI use were excluded, only a small proportion of NHRs were potential candidates for antimuscarinic treatment (6.6% with OAB or UI, 6.2% with UI). CONCLUSIONS: This study advances understanding of the challenges in prescribing antimuscarinic treatment safely and appropriately in elderly NHRs with a high prevalence of drug interactions, underlying MSCI, and SMI.

Brain health: the importance of recognizing cognitive impairment: an IAGG consensus conference.

Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States' Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient's right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline.

Comparison of the short test of mental status and the mini-mental state examination in mild cognitive impairment.

BACKGROUND: The Mini-Mental State Examination (MMSE) is the most widely used brief screening measure of cognition, but it is not sensitive in detecting mild memory or other cognitive impairments. The Short Test of Mental Status (STMS) was specifically developed for use in dementia assessment and was intended to be more sensitive to problems of learning and mental agility that may be seen in mild cognitive impairment (MCI). OBJECTIVE: To compare the STMS and MMSE for detecting or predicting MCI. DESIGN: Comparison of STMS and MMSE scores at baseline among 4 groups of patients: 788 patients with stable normal cognition, 75 patients with normal cognition at baseline but who developed incident MCI or Alzheimer disease during follow-up, 129 patients with prevalent MCI at baseline, and 235 patients with prevalent mild Alzheimer disease. All patients and control subjects for this study were evaluated through the Mayo Alzheimer's Disease Patient Registry or the Mayo Clinic Alzheimer's Disease Research Center, Rochester, Minn, using a standardized diagnostic approach. RESULTS: The STMS was slightly more sensitive than the MMSE in discriminating between patients with stable normal cognition and patients with prevalent MCI. The STMS was superior to the MMSE in detecting deficits in cognition in individuals who had normal cognition at baseline but later developed incident MCI or Alzheimer disease. CONCLUSIONS: Compared with the MMSE, the STMS was better able to document MCI and was more sensitive in detecting deficits in cognition in individuals who had normal cognition at baseline but later developed incident MCI or Alzheimer disease.