Alzheimer S Dementia - 2021 - Rahman - Rural Urban Differences in Diagnostic Incidence and Prevalence of Alzheimer S

Received: 12 September 2020 Revised: 2 November 2020 Accepted: 4 December 2020
DOI: 10.1002/alz.12285
F E AT U R E D A R T I C L E
Rural-urban differences in diagnostic incidence and prevalence

of Alzheimer’s disease and related dementias
Momotazur Rahman Elizabeth M. White Caroline Mills Kali S. Thomas

Eric Jutkowitz
Department of Health Services, Policy and

Practice, Brown University School of Public Abstract
Health, Providence, Rhode Island, USA
Introduction: Understanding rural-urban variation in the diagnostic incidence and
Correspondence prevalence of Alzheimer’s disease and related dementias (ADRD) will inform policies
Momotazur Rahman, PhD, 121 South Main to improve timely diagnosis and access to supportive services for older adults in rural
Street, S-6, Providence, RI 02912, USA.
Email: [email protected] communities.
Methods: Using 2008 to 2015 national claims data for fee-for-service Medicare ben-
eficiaries (roughly 170 million person-years), we computed unadjusted and adjusted
diagnostic incidence and prevalence estimates for ADRD in metropolitan, micropoli-
tan, and rural counties, and examined differences in survival rates.
Results: Risk-adjusted ADRD diagnostic incidence was higher in rural versus
metropolitan counties despite lower prevalence. Among beneficiaries diagnosed with
ADRD in 2008, metropolitan county residents experienced longer survival compared
to residents in rural and micropolitan counties.
Discussion: These data suggest that older adults in rural communities may be under-
diagnosed with ADRD, and/or diagnosed at later stages of dementia. Further work is
needed to develop strategies to reduce this disparity.
KEYWORDS
ADRD, diagnostic incidence, diagnostic prevalence, rural-urban disparity
1 BACKGROUND The expected increase in incidence and prevalence of ADRD is

particularly concerning for rural areas where healthcare capacity is
Alzheimer’s disease and related dementias (ADRD) affect roughly 14% limited. There is growing evidence that disparities in disease bur-
of adults over age 70 and more than 37% of adults aged 90 and den as well as availability, accessibility, affordability, and acceptabil-
older.1 Older adults are disproportionally represented among rural ity of healthcare exist among older adults living in rural areas, thus
populations,2 suggesting that rural regions of the country may be dis- contributing to the growing gap in life expectancy and survival wit-
proportionally affected by ADRD in current and coming years as the nessed between urban and rural communities.5–8 As the population
population of older Americans grows. Additionally, individuals living in ages, there is also expected to be a decrease in the availability of
rural areas have higher rates of risk factors for ADRD, including chronic family and other informal caregivers who provide over 18 billion
health conditions (eg, diabetes, obesity, depression), lifestyle factors hours of unpaid care annually to people with ADRD.9 A decline in
such as alcohol and tobacco use, and lower educational attainment.2–4 caregiver availability will increase demand for formal supportive ser-
Yet, little is known about differences in ADRD incidence and preva- vices, yet availability and access to such services is limited in rural
lence between rural and urban-dwelling Americans. areas.2,10,11
Alzheimer’s Dement. 2021;17:1213–1230. wileyonlinelibrary.com/journal/alz © 2021 the Alzheimer’s Association 1213

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1214 RAHMAN ET AL .
2 METHODS
RESEARCH IN CONTEXT
2.1 Data sources
1. Systematic review: Rural-urban differences in the preva-
lence of Alzheimer’s disease and related dementias
We used 2007 to 2015 FFS Medicare enrollment and Part A data.
(ADRD) have been examined in only two previous stud-
The Medicare Beneficiary Summary File (MBSF) contains enrollment
ies, cited in this article. One found higher prevalence in
data on all beneficiaries enrolled in or entitled to Medicare per year.
rural versus urban communities in 2000 but no differ-
It includes a Chronic Condition Warehouse (CCW) section with annual
ence in 2010, based on self and proxy reporting, while
flags for 27 chronic conditions and 33 other chronic or potentially dis-
another using Medicare data found lower adjusted diag-
abling conditions. All conditions also have the date of the first diagno-
nostic prevalence in rural compared with urban counties.
sis. We linked these data with Medicare Part A inpatient, skilled nursing
2. Interpretation: Following the latter study, we expected
facility (SNF) and home health (HHA) claims.
lower diagnostic ADRD incidence and prevalence in rural
We linked the Medicare data with the nursing home Minimum Data
areas in Medicare data due to underdiagnosis, since the
Set (MDS) and home health Outcome and Assessment Information
relative risk of dementia is similar, if not higher, in rural
Set (OASIS) to identify beneficiaries’ settings of care. The MDS is a
versus urban communities.
federally-mandated assessment tool for all residents in Medicare- or
3. Future directions: These results will inform efforts to
Medicaid-certified nursing homes, completed at admission and at least
improve ADRD screening to ensure timely diagnosis for
quarterly thereafter. OASIS home healthcare assessments are com-
older rural adults, so they may access supportive services
pleted at start of care, 60-day follow-ups, and discharge (and surround-
and plan for long-term care needs, and will also provide
ing an inpatient or nursing facility stay).
data and background for larger studies to develop strate-
These data all informed our Residential History File,12,13 a per-
gies to reduce rural-urban disparities.
person chronological history of health service utilization and location
of service based on claims and assessment data.
2.2 Study cohort

Highlights
We examined all Medicare beneficiaries over the age of 65 who were
∙ ADRD diagnostic incidence was higher in rural vs.
enrolled in FFS Medicare between 2007 and 2015. For each year of
metropolitan counties.
observation, we excluded beneficiaries enrolled in Medicare Advan-
∙ ADRD diagnostic prevalence was lower in rural vs.
tage in that year or the prior year because their diagnoses and health-
metropolitan counties.
care utilization could not be identified. We calculated incidence and
∙ The share of decedents with ADRD diagnosis was lower in
prevalence measures for 2008 to 2015, but used 2007 data as our prior
rural vs. metropolitan counties.
year lookback window for 2008.
∙ Survival following ADRD diagnosis was lower in rural vs.
metropolitan counties
2.3 ADRD
We identified Medicare beneficiaries with ADRD, our main outcome

This study aims to assess differences in the diagnostic incidence and variable, using the CCW flag for Alzheimer’s Disease, Related Disor-
prevalence of ADRD between metropolitan, micropolitan, and rural ders, or Senile Dementia. This flag captures 24 ICD-9 codes (for claims
counties, and determine whether these differences are explained by submitted prior to October 1, 2015) or 22 ICD-10 codes (for claims
underlying beneficiary demographics, prior healthcare utilization, and on or after October 1, 2015) for dementia present on one or more
comorbid illness. Of note, we did not aim to measure actual ADRD inpatient, SNF, HHA, hospital outpatient, or carrier claim over a 3-year
incidence and prevalence as determined by specific diagnostic crite- lookback. Compared to clinically-diagnosed cases of dementia in the
ria as has been done through prospective cohort studies like the Aging, ADAMS study, the CCW ADRD algorithm had a sensitivity of 0.85 and
Demographics, and Memory Study (ADAMS).1 Rather, we used 2007 specificity of 0.89.14 Validation studies in other populations have mea-
to 2015 Medicare claims to understand diagnostic patterns, broadly, sured sensitivity between 0.51 and 0.85 and specificity between 0.77
in the entire fee-for-service (FFS) Medicare population. We also per- and 0.92.15,16
formed a survival analysis of FFS Medicare beneficiaries who were For each year of observation, we used the annual CCW flags and
diagnosed with ADRD in 2008 to examine rural-urban differences in the associated date of the first diagnosis to classify beneficiaries as not
10-year survival rates. diagnosed with ADRD, newly diagnosed with ADRD in that year (ie,
RAHMAN ET AL . 1215
study year is the same as the year of first diagnosis), or started the year nosed with ADRD, newly diagnosed with ADRD, or started the year
with an ADRD diagnosis (ie, study year is greater than the year of the with a diagnosis of ADRD). The main explanatory variables were cate-
first diagnosis). Because CCW flags are based on claims since 1999, the gories for rurality (metropolitan, micropolitan, or rural). We controlled
earliest possible date of ADRD diagnosis is January 1, 1999. for beneficiaries’ demographics, comorbidities, healthcare utilization,
and zip code characteristics. Second, we calculated the adjusted like-
lihood of each category of outcome as the marginal effects of rurality
2.4 Metropolitan, micropolitan, and rural categories (margins command in Stata). We performed these two steps
residence for each year. We then plotted these predictive margins for a given out-
come by year. An illustration of detailed steps of risk adjustment for
We used the MBSF to determine each Medicare beneficiary’s county year 2015 is presented in Appendix Table 4.
of residence. We then used the rural urban continuum codes (RUCC) to In the second part of our analysis, we compared Medicare ben-
determine the rurality of a beneficiary’s county: metropolitan (RUCC eficiaries in metropolitan, micropolitan, and rural counties who died
1 to 3), micropolitan (RUCC 4 to 7) and rural (RUCC 8 and 9).5,8,17,20 between 2008 and 2015. We calculated the share of those who had
Detailed codes are presented in Appendix Table 1. an ADRD diagnosis (either new or existing) among all decedents, by
the year of death. Finally, among the persons who were diagnosed with
ADRD in 2008, we compared the probability of survival over ten years
2.5 Covariates from the date of diagnosis for metropolitan, micropolitan, and rural
counties. Here we focused on incident cases in 2008 because they had
Beneficiary demographic characteristics (sex, race, and Medicaid eli- the longest follow-up in our dataset. In this survival analysis, the event
gibility) came from the MBSF. We classified beneficiaries’ comorbidi- is death. The cases were tracked at the end of 2017. Our survival anal-
ties using two measures1 : a count of chronic and potentially disabling ysis involves two steps. First, we estimated a Cox proportional hazards
conditions identified in the CCW file for the previous year, and2 a model (stcox command in Stata) including rurality indicators and the
hierarchical chronic condition (HCC) score derived from ICD-9 codes same set of covariates as described above in the Cox regression model.
reported on all Part-A claims during the previous year. As an additional Second, we plotted the survival function (stcurve command in Stata) for
measure of clinical complexity, we also computed summary measures metropolitan, micropolitan, and rural counties. Stata, version 15.1, was
of each beneficiary’s healthcare utilization in the prior year,21,22 includ- used for all statistical analysis.
ing the number of inpatient hospital admissions, days in a nursing home,
and a count of home health assessments. The main reason for includ-
ing prior healthcare utilization and comorbidities as risk adjusting vari- 3 RESULTS
ables is to ensure that differences in ADRD prevalence between rural
and urban counties are not just a reflection of differences in overall We examined approximately 170 million person-years for Medicare
health. Finally, to characterize beneficiaries’ residential neighborhood, FFS beneficiaries, 76% of whom (person-years) were in metropolitan
we determined the share of Medicare beneficiaries eligible for Medi- counties, 14% in micropolitan counties, and 10% in rural counties. Ben-
caid and the share of beneficiaries enrolled in Medicare Advantage for eficiaries residing in nonmetropolitan counties were slightly younger,
each beneficiary’s zip code. less likely to be female and white, and had slightly fewer chronic con-
ditions (Table 1), though the HCC score derived from inpatient claims
was similar across all counties. Rural beneficiaries spent more time in
2.6 Statistical analysis nursing homes compared to beneficiaries residing in metropolitan and
micropolitan counties. These differences were fairly consistent across
Change in ADRD prevalence at a given point of time is determined by non-ADRD, new-ADRD and existing ADRD cases (Appendix Table 2).
two factors: new incident cases and deaths in the population. In the Unadjusted diagnostic incidence and prevalence were higher in
first part of our analysis, we examined how the new inflow of ADRD metropolitan counties compared to micropolitan and rural counties
cases differed from the existing population of ADRD cases in rural and throughout the study period (left panels of Figure 1). Between 2008
urban counties. The diagnostic incidence is the percent of Medicare and 2015, ADRD diagnostic incidence declined, though there were
beneficiaries newly diagnosed with ADRD in a given year. The diagnos- small spikes in new diagnoses in 2012 and 2015. At the same time, diag-
tic prevalence is the percent of Medicare beneficiaries who started a nostic prevalence increased from 2008 to 2010, generally plateaued
given year with a diagnosis of ADRD. For both measures, the denomi- from 2010 to 2013, then decreased from 2013 to 2015. After adjust-
nator consists of the entire FFS over age 65 Medicare population as of ment for beneficiary and zip code characteristics, incidence was higher
January 1 of a given year. We plotted these measures for the years in rural and micropolitan counties compared to metropolitan counties
2008 to 2015 stratified by county rurality (metropolitan, micropolitan, (right panels of Figure 1). The difference in prevalence between rural
vs rural). We calculated risk-adjusted incidence and prevalence using and urban counties was also reduced substantially after risk adjust-
two steps. First, we estimated a multinomial logistic regression (mlogit ment (from 1 percentage point in the unadjusted rate to 0.5 percentage
command in Stata) in which the outcome was ADRD status (ie, not diag- points following adjustment).
1216 RAHMAN ET AL .
TA B L E 1 Characteristics of Medicare beneficiaries enrolled in fee-for-service Medicare between 2008 and 2015
Metropolitan Micropolitan Rural

counties counties counties
Person-years (N) 129,624,353 23,649,523 17,282,079
Age in calendar year, mean 76.9 76.5 76.4
Female (%) 58.4% 57.1% 56.2%
Black (%) 7.7% 4.6% 4.7%
Hispanic (%) 5.2% 2.4% 1.7%
Other race (%) 3.7% 1.8% 1.7%
Dual eligible (%) 12.1% 13.0% 15.6%
No. of chronic conditions, mean 4.22 4.01 3.86
HCC score, mean 0.66 0.64 0.64
No. of hospitalized days, mean 0.28 0.29 0.31
No. of nursing home days, mean 9.00 10.15 11.45
No. of home health assessments, mean 0.23 0.21 0.23
Residential ZIP code Medicare Advantage penetration (%) 23.03 15.46 13.32
Residential ZIP code dual-eligible rate (%) 16.17 18.15 19.79
Abbreviation: HCC, hierarchical chronic conditions.
Differences in diagnostic prevalence and incidence between rural last year of life compared to decedents in metropolitan and micropoli-
and urban counties can perhaps be better understood in terms of risk tan counties.
and prevalence ratios. For example, the adjusted diagnostic incidence Among decedents with ADRD, age at death was 0.5 years younger
is about 1.14 times higher in rural versus urban counties and 1.08 and age at diagnosis of ADRD was 0.4 years younger in micropoli-
times higher in micropolitan versus urban counties. Conversely, the tan/rural counties compared to metropolitan counties (Appendix Table
adjusted diagnostic prevalence is about 0.93 times lower in rural ver- 3). As a result, the mean time from diagnosis to death was about 40 days
sus urban counties and 0.95 times lower in micropolitan versus urban shorter in rural/micropolitan counties compared to metropolitan coun-
counties. These ratios were fairly stable over time (Appendix Figures 1 ties (Appendix Table 3).
and 2). In the survival analysis, out of the 655,440 subjects, 556,136 experi-
Appendix Figure 3 compares ADRD diagnostic incidence and preva- enced the event of death. To evaluate the proportional hazard assump-
lence between rural and urban counties in different regions of the tion, we assessed Kaplan-Meier observed versus expected survival
US in 2015. In general, patterns are fairly similar across regions. We curves, which appeared to be quite close for each type of county imply-
observed a lower unadjusted incidence and prevalence in rural coun- ing that the rurality variable satisfies the proportional hazard assump-
ties, a higher adjusted incidence in rural counties, and a decline in the tion. We evaluated the fit of the model by using the Cox-Snell residu-
rural-urban difference in prevalence after adjustment. als. We graphed the Nelson-Aalen cumulative hazard function and the
Between 2008 and 2015, there was an increase in the share of Medi- Cox-Snell residuals so that we can compare the hazard function to the
care beneficiaries dying with ADRD across metropolitan, micropoli- diagonal line. The hazard function follows the 45 degree line, implying
tan, and rural counties (Figure 2). In unadjusted analyses, a larger per- that it approximately has an exponential distribution with a hazard rate
centage of decedents in metropolitan and micropolitan counties had of one and that the model fits the data well.
ADRD compared to decedents in rural counties (metropolitan coun- Figure 3 plots the adjusted likelihood of survival in days following
ties were about four percentage points higher than rural counties in all ADRD diagnosis in 2008 in the different types of counties. The adjusted
years). In adjusted analyses, the overall trends remained consistent but share of beneficiaries who survived 365 days following diagnosis was
the difference in prevalence between metropolitan and rural counties 80% in metropolitan counties and 79% in rural and micropolitan coun-
decreased. Similar to diagnostic prevalence ratios in the entire popula- ties. This implies that 365-day survival rates were about 1.013 times
tion, adjusted prevalence among decedents was about 0.92 times lower or 1% higher in metropolitan counties compared to nonmetropolitan
in rural counties and 0.95 times lower in micropolitan counties relative counties. The adjusted share of beneficiaries who survived 2555 days
to urban counties (Appendix Figure 4). Table 2 displays the character- (ie, 7 years) following diagnosis was 24% in metropolitan counties and
istics of decedents in metropolitan, micropolitan, and rural counties. 21% in rural and micropolitan counties. The 2555-day survival rates
Average age at death was 0.7 years lower in micropolitan/rural coun- were about 14% (ie, 1.14 times) higher in metropolitan counties com-
ties compared to metropolitan counties. Decedents in rural counties pared to nonmetropolitan counties. Thus, the gap in likelihood of sur-
spent significantly more days in hospitals and nursing homes during the vival between rural/micropolitan and metropolitan counties increased
RAHMAN ET AL . 1217
F I G U R E 1 Diagnostic incidence and prevalence of Alzheimer’s disease and related dementias (ADRD) in urban and rural counties in the US
from 2008 to 2015. (A) ADRD diagnostic incidence. (B) ADRD diagnostic prevalence. Adjusted measures and the 95% confidence intervals are
estimated separately for each year using two steps. First, we estimate a multinomial logit regression of ADRD diagnosis onto rurality of
beneficiary’s residential county, beneficiary’s demographic, clinical and residential zip code characteristics (listed in Table 1). Second, we estimate
the marginal effects of rurality. Abbreviations: Metro, metropolitan counties; Micro, micropolitan counties; Rural, rural counties
1218 RAHMAN ET AL .
F I G U R E 2 Proportion of deceased Medicare beneficiaries with Alzheimer’s disease and related dementias (ADRD), 2008 to 2015. Adjusted
measures and the 95% confidence intervals are estimated separately for each year using two steps. First, we estimate a logit regression of ADRD
diagnosis onto rurality of beneficiary’s residential county, beneficiary’s demographic, clinical and residential zip code characteristics (listed in
Table 2). Second, we estimate the marginal effects of rurality. Abbreviations: Metro, metropolitan counties; Micro, micropolitan counties; Rural,
rural counties
over the follow-up years. We observed similar patterns in terms unad- overall declining ADRD diagnostic incidence are consistent with pre-
justed survival curves as well. vious findings of declining dementia incidence among participants of
the Framingham Heart Study.24 Both the Framingham and Health and
Retirement Studies cited an increase in educational attainment as par-
4 DISCUSSION tial explanation for the trends they observed.
We found a significant increase in the proportion of deceased
To our knowledge, this is the first national prospective cohort study Medicare beneficiaries with ADRD between 2008 and 2015, com-
to assess differences in ADRD diagnostic prevalence and incidence porting with existing evidence from the Centers for Disease Con-
between metropolitan, micropolitan, and rural counties in the United trol and Prevention (CDC) showing an increase in mortality rates due
States. We found that, while unadjusted estimates suggest lower inci- to Alzheimer’s disease over time.25 Importantly, our findings reflect
dence and prevalence of ADRD in rural counties, after adjustment, the proportion of Medicare beneficiaries who died with ADRD as
ADRD incidence was higher in rural counties compared to metropoli- captured on a lookback of claims data, rather than as reported on
tan counties, despite lower prevalence in these rural counties. We also death certificates as an underlying cause of death, which is what the
found that beneficiaries with ADRD in metropolitan counties typically CDC uses. Our estimates are significantly higher than the CDC esti-
had a longer survival following diagnosis compared to beneficiaries mates, which is likely due to dementia being underreported on death
with ADRD in rural and micropolitan counties. certificates.26 Additionally, the CDC estimates are only for Alzheimer’s
ADRD diagnostic prevalence in the overall FFS Medicare popula- disease, whereas the CCW algorithm for Medicare claims captures
tion increased from 2008 to 2010, plateaued from 2010 to 2013, then multiple types of dementia.
declined from 2013 to 2015. Prevalence in 2015 was lower than in Variations in prevalence and incidence measures over time can
2008, though this decline was more prominent in metropolitan coun- be driven by multiple factors, not all of which are fully understood.
ties versus micropolitan and rural counties. This overall trend is simi- Because we used Medicare data, we also have to consider how changes
lar to previous findings from the Health and Retirement Study23 which in administrative policies over time may have affected the coding of
demonstrated a decline in dementia prevalence between two time ADRD in claims. For example, the Centers for Medicare and Medi-
points, 2000 and 2012. At the same time, we found a general decline caid Services (CMS) expanded the allowable number of diagnosis codes
in diagnostic incidence of ADRD between 2008 and 2015, despite hospitals could report from 9 to 25 in 2011, which has increased
some slight disruptions in that trend in 2012 and 2015. Our findings of the reported number of comorbidities in hospital claims.27 This could
RAHMAN ET AL . 1219
TA B L E 2 Characteristics of Medicare beneficiaries who died between 2008 and 2015
Metropolitan Micropolitan Rural

counties counties counties
N 7,609,611 1,403,745 1,036,497
Age at death, mean 82.7 82.0 81.9
Female (%) 56.13% 54.58% 53.67%
Black (%) 8.47% 5.29% 5.45%
Hispanic (%) 4.46% 2.01% 1.47%
Other race (%) 2.56% 1.57% 1.65%
Dual eligible (%) 20.94% 24.44% 28.14%
No. of Chronic Conditions, mean 6.34 6.06 5.93
HCC score, mean 1.40 1.31 1.29
No. of Hospitalization Days, mean 0.93 0.91 0.98
No. of Nursing Home Days, mean 47.03 52.08 57.17
No. of Home Assessments, mean 0.75 0.70 0.72
Residential zip code Medicare Advantage penetration (%) 23.65 15.84 13.72
Residential zip code dual-eligible rate (%) 16.87 18.78 20.42
Abbreviation: HCC, hierarchical chronic conditions.
potentially explain why we saw a spike in ADRD diagnostic incidence

in 2012. Similarly, the spike in incident ADRD diagnoses in 2015 could
potentially be due to the transition from ICD-9 to ICD-10, though this
would have only affected claims after October 1, 2015, when ICD-
10 took effect. Another policy change that may have increased clini-
cal diagnoses of ADRD was the introduction of the annual Medicare
wellness visit in 2011, which has enabled primary care providers to be
reimbursed for preventative care, including a screening for cognitive
impairment. This may also partially explain the spike in diagnostic inci-
dence we found in 2012.
Our findings are similar to those by Abner and colleagues who, also
using Medicare data, found that rural counties in Kentucky and West
Virginia had lower adjusted diagnostic ADRD prevalence than urban
counties in the same states.28 However, our findings differ from those
of Weden and colleagues29 who found that the unadjusted dementia
prevalence was higher in rural communities than urban communities
(5.1% vs 4.4%) in 2010. They also found higher prevalence of cognitive
impairment with no dementia (CIND) in rural versus urban communi-
ties (16.5% vs 14.9%). For that same year, we found that the unadjusted
dementia prevalence was lower in rural counties than urban counties
F I G U R E 3 Adjusted survival functions among beneficiaries newly
(10.3% vs 11.7%). These differences are likely to be driven by differ-
diagnosed with Alzheimer’s disease and related dementias (ADRD) in
ences in measurement and classification of dementia between the two
2008. Survival functions are plotted based on Cox regression onto
rurality of beneficiary’s residential county, beneficiary’s demographic, studies. Weden et al. used data from the Health and Retirement Study,
clinical and residential zip code characteristics (listed in Table 1). which relies on telephonic cognitive assessments with self or proxy
Detailed results of the Cox regression are presented in Appendix Table reporting and the ADAMS dementia classification methodology.30 We
5. Second, we estimate the marginal effects of rurality. Lines for rural identified dementia cases using the CCW indicator in Medicare claims,
(green) and micropolitan (red) counties are almost identical and
which is derived from an algorithm that has been validated against the
overlapping in this figure. Abbreviations: Metro, metropolitan
counties; Micro, micropolitan counties; Rural, rural counties ADAMS classification for dementia, but not for CIND. Medicare claims
do not have separate indicators for CIND or mild cognitive impair-
ment, so some of the discrepancy in unadjusted prevalence between
our study results may be related to misclassification. Despite these
1220 RAHMAN ET AL .
differences in unadjusted prevalence, the risk adjustment models in If ADRD diagnosis is associated with Medicare Advantage enrollment,
both studies move the estimated rural-urban difference in the same lower Medicare Advantage penetration in rural counties may bias our
direction. estimates. We tried to minimize this bias by including Medicare Advan-
Rural-urban differences between our adjusted and unadjusted esti- tage penetration of beneficiary’s residential zip code in our models.
mates are driven by several factors. First, age at ADRD diagnosis is Finally, we cannot measure many risk factors that may be associated
about six months younger in rural and micropolitan counties com- with ADRD and vary by rurality such as life expectancy, education, and
pared to metropolitan counties (see Appendix Table 2 for newly diag- healthcare access.
nosed beneficiaries and Appendix Table 3 for decedents). As a result, In conclusion, we found higher adjusted diagnostic incidence, but
adjusting for differences in age distribution between metropolitan, not unadjusted diagnostic incidence in rural counties compared to
micropolitan, and rural counties alone reduces the gap in ADRD diag- metropolitan counties, suggesting underdiagnosis of ADRD in rural
noses (Appendix Figure 5). Second, it is possible that underdiagnosed areas. We also found lower diagnostic prevalence and shorter time
ADRD is more prevalent in micropolitan and rural counties compared to death following ADRD diagnosis in rural counties compared to
to metropolitan counties. Additionally, both Abner et al.28 and Weden metropolitan counties, suggesting that rural beneficiaries may be diag-
et al.29 found fewer chronic conditions diagnosed in rural counties nosed at later stages of disease. These rural-urban disparities raise
compared to metropolitan counties. In our data, we observed the num- unique challenges for policymakers given the declining availability of
ber of chronic conditions to be about five percent lower despite higher formal support services2,10,11 and primary care providers7,31 in rural
healthcare utilization in rural beneficiaries compared to the urban areas. Further research is needed to better understand the factors
beneficiaries (Tables 1 and 2). Abner et al.28 interpreted this lower driving underdiagnosis of ADRD among rural residents.
comorbidity as underdiagnosis of chronic conditions in nonmetropoli-
tan counties. As in the prior studies, we included the number of chronic ACKNOWLEDGMENTS
conditions as a risk-adjusting variable because it is an important predic- This project was funded by grants from the National Institute on Aging,
tor of ADRD diagnosis. Additionally, because both ADRD and chronic No. R03 AG054687-01 and No. P01AG027296.
conditions are likely to be underreported in rural counties, the bias in
rural-urban difference in ADRD due to underreporting is likely to be CONFLICT OF INTEREST
smaller in the adjusted model when the number of chronic conditions The authors declare there are no conflicts of interest or financial dis-
is included as a risk adjustor. closures.
The most perplexing aspect of our findings is that we observed lower

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2018;37(8):1274-1281. How to cite this article: Rahman M, White EM, Mills C,
23. Langa KM, Larson EB, Crimmins EM, et al. A comparison of the preva-
Thomas KS, Jutkowitz E. Rural-urban differences in diagnostic
lence of dementia in the United States in 2000 and 2012. JAMA Intern
Med. 2017;177(1):51-58. incidence and prevalence of Alzheimer’s disease and related
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Study. N Engl J Med. 2016;374(6):523-532.
RAHMAN ET AL .
Alzheimer’s disease and related dimentias (ADRD) prevalence ratios among Medicare fee-for-service (FFS) beneficiaries
Alzheimer’s disease and related dimentias (ADRD) incidence ratios among Medicare fee-for-service (FFS) beneficiaries
FIGURE A1
FIGURE A2
APPENDIX
1222
RAHMAN ET AL . 1223
F I G U R E A 3 Diagnostic incidence and prevalence of Alzheimer’s disease and related dimentias (ADRD) among Medicare fee-for-service (FFS)
beneficiaries in urban and rural counties in 2015 across different regions of the US. (A) Percent of Medicare FFS beneficiaries newly diagnosed
with ADRD in 2015. (B) Percent of Medicare FFS beneficiaries that started 2015 with an ADRD diagnosis
RAHMAN ET AL .
Alzheimer’s disease and related dimentias (ADRD) prevalence ratios among deceased Medicare fee-for-service (FFS)
FIGURE A4
beneficiaries
1224
RAHMAN ET AL . 1225
F I G U R E A 5 Diagnostic incidence and prevalence of Alzheimer’s disease and related dimentias (ADRD) among Medicare fee-for-service (FFS)
beneficiaries in 2015 with different levels of risk adjustment. (A) Percent of Medicare FFS beneficiaries newly diagnosed with ADRD in 2015. (B)
Percent of Medicare FFS beneficiaries that started 2015 with an ADRD diagnosis
1226 RAHMAN ET AL .
TA B L E A 1 Rurality categories of counties
RUCC 2013 Description Category

1 Metro - Counties in metro areas of 1 million population or more Metro
2 Metro - Counties in metro areas of 250,000 to 1 million population Metro
3 Metro - Counties in metro areas of fewer than 250,000 population Metro
4 Nonmetro - Urban population of 20,000 or more, adjacent to a metro area Micro
5 Nonmetro - Urban population of 20,000 or more, not adjacent to a metro area Micro
6 Nonmetro - Urban population of 2500 to 19,999, adjacent to a metro area Micro
7 Nonmetro - Urban population of 2500 to 19,999, not adjacent to a metro area Micro
8 Nonmetro - Completely rural or less than 2500 urban population, adjacent to a metro area Rural
9 Nonmetro - Completely rural or less than 2500 urban population, not adjacent to a metro area Rural
Abbreviation: RRUC, rural urban continuum code.
TA B L E A 2 Characteristics of Medicare beneficiaries enrolled in fee-for-service Medicare between 2008 and 2015 by ADRD status
ADRD Status
Newly diagnosed with ADRD in Started the observation year
No ADRD diagnosis the observation year with ADRD diagnosis
Metro Micro/Rural Metro Micro/Rural Metro Micro/Rural
Person-years (N) 111,000,409 35,626,357 3,758,537 1,131,654 14,865,407 4,173,591
Age in calendar year, mean 75.9 75.6 81.9 81.4 83.3 82.9
Female (%) 57.1% 55.4% 62.1% 61.2% 67.2% 67.0%
Black (%) 7.3% 4.4% 8.5% 5.7% 9.9% 6.7%
Hispanic (%) 5.1% 2.1% 5.0% 2.0% 5.8% 2.2%
Other race (%) 3.8% 1.8% 3.0% 1.6% 3.1% 1.5%
Dual eligible (%) 9.9% 11.6% 17.6% 22.7% 27.3% 32.6%
No. of Chronic Conditions, mean 3.77 3.56 7.47 7.10 6.77 6.40
HCC score, mean 0.59 0.59 0.91 0.89 1.08 1.03
No. of Hospitalization Days, mean 0.22 0.25 0.48 0.50 0.69 0.69
No. of Nursing Home Days, mean 2.09 2.95 11.02 15.43 60.13 75.50
No. of Home Assessments, mean 0.15 0.15 0.50 0.51 0.74 0.69
Residential zip code Medicare Advantage 23.0% 14.6% 23.2% 14.4% 23.5% 14.6%
penetration (%)
Residential zip code dual eligible rate (%) 16.0% 18.7% 16.9% 19.6% 17.4% 19.9%
Note: These mean values are based on beneficiary year level data. Number of chronic conditions is calculated from the chronic condition warehouse (CCW)
data segment of the beneficiary summary file. Community based HCC score was calculated using part-A claims data using algorithm provided by the Centers
for Medicare and Medicaid Services. Care use rates are calculated using residential history algorithm applying claims and assessment data from the previous
year.
Abbreviations: ADRD, Alzheimer’s disease and related dementias; HCC, hierarchical chronic conditions.
RAHMAN ET AL . 1227
TA B L E A 3 Characteristics of Medicare beneficiaries who died between 2008 and 2015 with and without ADRD diagnosis
Non-ADRD ADRD
Metro Micro/Rural Metro Micro/Rural
Person-years (N) 4,061,189 1,398,525 3,548,422 1,041,717
Age at death, mean 80.1 79.6 85.7 85.2
Female (%) 50.3% 48.2% 62.8% 62.2%
Black (%) 7.9% 4.8% 9.1% 6.2%
Hispanic (%) 4.5% 1.8% 4.4% 1.8%
Other race (%) 2.8% 1.8% 2.3% 1.4%
Dual eligible (%) 15.6% 19.9% 27.1% 34.2%
No. of Chronic Conditions, mean 5.59 5.38 7.19 6.84
HCC score, mean 1.36 1.28 1.44 1.33
No. of Hospitalization Days, mean 0.88 0.91 0.99 0.97
No. of Nursing Home Days, mean 16.83 20.78 81.59 99.15
No. of Home Assessments, mean 0.64 0.63 0.89 0.82
Residential zip code Medicare Advantage penetration (%) 23.7% 15.1% 23.6% 14.8%
Residential zip code dual eligible rate (%) 16.8% 19.2% 17.0% 19.9%
ADRD-specific variables
Age at diagnosis 82.9 82.5
No. of days survived following ADRD diagnosis 1383.4 1339.3
Note: These mean values are based on beneficiary year level data. Number of chronic conditions is calculated from the chronic condition warehouse (CCW)
data segment of the beneficiary summary file. Community based HCC score was calculated using part-A claims data using algorithm provided by the Centers
for Medicare and Medicaid Services. Care use rates are calculated using residential history algorithm applying claims and assessment data from the previous
year.
Abbreviations: ADRD, Alzheimer’s disease and related dementias; HCC, hierarchical chronic conditions.
1228 RAHMAN ET AL .
TA B L E A 4 An illustration of how we calculated risk adjusted diagnostic incidence and prevalence
For each year, risk-adjusted incidence and prevalence are calculated using two steps.
Step 1: Estimate a multinomial logit model of Alzheimer’s disease and related dementias (ADRD) diagnosis status (variable name adrd: 0 = no ADRD
diagnosis, 1 = newly diagnosed with ADRD, 2 = started year with ADRD diagnosis) onto explanatory variables listed in Table 1 and rurality categories
(variable name: F1406709; 1 = metropolitan, 2 = micropolitan, and 3 = rural). Below is the estimation for 2015. Here the control variables are the
same as reported in Table 1 (Age in 2015, female indicator, indicators of different races: Black, Hispanic and other race, dual eligibility indicator,
number of chronic conditions, hierarchical chronic conditions (HCC) score, number of hospitalized days, number of nursing home days, number of
home health assessments, Medicare Advantage penetration in residential zip code and share of dual eligible in residential zip code).
. mlogit adrd age hksex black hispanic orace dual No_CCW_CC HCC_Community Hosp_count_PY Total_NH_Days_PY HHA_Assmnt_PY shma shdual
i.F1406709
Iteration 0: log likelihood = -9990884.3
Multinomial logistic regression Number of obs = 21,446,383
LR chi2(30) = 5298058.90
Prob > chi2 = 0.0000
Log likelihood = -7341854.9 Pseudo R2 = 0.2651
Adrd Coef. Std. Err. z P > |z| [95% Conf. Interval]
0 (base
outcome)
Age .0875532 .0001844 474.86 0.000 .0871918 .0879146
Hksex .1150767 .0028127 40.91 0.000 .1095638 .1205896
Black .1244485 .0053954 23.07 0.000 .1138736 .1350234
Hispanic −.0981258 .007341 −13.37 0.000 −.1125139 −.0837378

Orace −.1037752 .0083075 −12.49 0.000 −.1200577 −.0874928
Dual .3544636 .0040938 86.58 0.000 .3464398 .3624873
No_CCW_CC .4018247 .0004737 848.32 0.000 .4008964 .4027531
HCC_Community −.1036427 .002543 −40.76 0.000 −.1086269 −.0986586

Hosp_count_PY −.1042952 .002525 −41.31 0.000 −.109244 −.0993463
Total_NH_Days_PY .0042147 .0000371 113.46 0.000 .0041419 .0042875
HHA_Assmnt_PY .0571485 .0012526 45.62 0.000 .0546935 .0596035
Shma −.0984688 .0110809 −8.89 0.000 −.1201869 −.0767507

Shdual −.0167419 .0147715 −1.13 0.257 −.0456935 .0122097
F1406709
2 .054408 .0041051 13.25 0.000 .0463622 .0624538
3 .1059648 .0047921 22.11 0.000 .0965726 .1153571
_cons −12.67833 .0158433 −800.23 0.000 −12.70938 −12.64728

2
Age .1136594 .0001113 1021.18 0.000 .1134412 .1138775
Hksex .1799482 .0017415 103.33 0.000 .1765349 .1833615
Black .1991068 .0032032 62.16 0.000 .1928287 .2053849
Hispanic .0013809 .0041882 0.33 0.742 −.0068278 .0095896
(Continues)
RAHMAN ET AL . 1229
TA B L E A 4 (Continued)
Orace −.1715693 .004912 −34.93 0.000 −.1811965 −.161942

Dual .8023836 .0023737 338.03 0.000 .7977313 .8070359
No_CCW_CC .2736333 .0002981 918.06 0.000 .2730491 .2742175
HCC_Community −.1242536 .0015052 −82.55 0.000 −.1272037 −.1213036

Hosp_count_PY .0684595 .0014101 48.55 0.000 .0656956 .0712233
Total_NH_Days_PY .0104315 .0000203 514.02 0.000 .0103917 .0104713
HHA_Assmnt_PY .1978542 .0007169 276.00 0.000 .1964492 .1992592
Shma .054728 .0067072 8.16 0.000 .041582 .0678739
Shdual −.1246478 .0089432 −13.94 0.000 −.1421761 −.1071194

F1406709
2 −.0434924 .0025471 −17.08 0.000 −.0484846 −.0385003

3 −.0575522 .0030114 −19.11 0.000 −.0634545 −.0516499
_cons −13.06908 .0096544 −1353.68 0.000 −13.088 −13.05016
Step 2: Generate predicted probabilities of each ADRD diagnosis status for different categories of rurality using predictive margins
. margins F1406709
Predictive margins Number of obs = 21,446,383
Model VCE: OIM
1._predict: Pr(adrd = = 0), predict(pr outcome(0))
Delta-method
Margin Std. Err. z P > |z| [95% Conf. Interval]
_predict#F1406709 |
1 1 .8645893 .0000712 1.2e+04 0.000 .8644497 .8647288
1 2 .8662672 .0001715 5051.37 0.000 .8659311 .8666033
1 3 .8660872 .0002069 4186.10 0.000 .8656816 .8664927
2 1 .0282892 .0000397 712.16 0.000 .0282113 .028367
2 2 .0300535 .0001005 298.93 0.000 .0298565 .0302506
2 3 .031596 .0001253 252.08 0.000 .0313503 .0318416
3 1 .1071216 .0000662 1619.33 0.000 .1069919 .1072512
3 2 .1036793 .0001588 653.04 0.000 .1033681 .1039905
3 3 .1023169 .0001901 538.35 0.000 .1019444 .1026894
Note: We performed these two steps for each year. We then plotted these predictive margins for a given outcome by year.
1230 RAHMAN ET AL .
TA B L E A 5 Detailed results of Cox regression for survival analysis rurality categories (variable name: F1406709; 1 = metropolitan,
2 = micropolitan, and 3 = rural). Here the control variables are the same as reported in Table 1 (Age in 2008, female indicator, indicators of
different races: Black, Hispanic and other race, dual eligibility indicator, number of chronic conditions, hierarchical chronic conditions (HCC) score,
number of hospitalized days, number of nursing home days, number of home health assessments, Medicare Advantage penetration in residential
zip code and share of dual eligible in residential zip code)
.stcox i.F1406709 age hksex black hispanic orace dual No_CCW_CC HCC_Community Hosp_count_PY Total_NH_Days_PY HHA_Assmnt_PY shma
shdual
failure _d: surv
analysis time _t: surv_days
Iteration 0: log likelihood= -7079801.6
Iteration 3: log likelihood= -6995383
Refining estimates:
Cox regression – Breslow method for ties
No. of subjects = 655,440 Number of obs = 655,440
No. of failures = 556,136
Time at risk =1031695650
LR chi2(15)= 168837.53
Log likelihood = -6995382.8 Prob > chi2 = 0.0000
_t Haz. Ratio Std. Err. Z P > |z| [95% Conf. Interval]
F1406709
2 1.004739 .0056723 0.84 0.402 .9936823 1.015918
3 .9252037 .004421 -16.27 0.000 .9165793 .9339094
Age 1.060842 .0002143 292.35 0.000 1.060422 1.061262
Hksex .7304632 .0020683 -110.92 0.000 .7264207 .7345282
black .9155114 .0048876 -16.53 0.000 .9059818 .9251413
hispanic .7045382 .0054185 -45.54 0.000 .6939978 .7152386
orace .6962504 .006804 -37.05 0.000 .6830418 .7097145
dual 1.030797 .0040088 7.80 0.000 1.02297 1.038684
No_CCW_CC 1.063543 .0005535 118.38 0.000 1.062459 1.064629
HCC_Community 1.307859 .0035458 99.00 0.000 1.300928 1.314828
Hosp_count_PY .9816694 .0017256 -10.52 0.000 .9782931 .9850574
Total_NH_Days_PY 1.001207 .0000206 58.51 0.000 1.001167 1.001248
HHA_Assmnt_PY 1.039136 .0011753 33.94 0.000 1.036835 1.041442
shma 1.012407 .0120466 1.04 0.300 .9890693 1.036295
shdual .875022 .0125622 -9.30 0.000 .8507438 .899993

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Received: 12 September 2020 Revised: 2 November 2020 Accepted: 4 December 2020

Rural-urban differences in diagnostic incidence and prevalence

Momotazur Rahman Elizabeth M. White Caroline Mills Kali S. Thomas

Department of Health Services, Policy and

1 BACKGROUND The expected increase in incidence and prevalence of ADRD is

Alzheimer’s Dement. 2021;17:1213–1230. wileyonlinelibrary.com/journal/alz © 2021 the Alzheimer’s Association 1213

2.2 Study cohort

We identified Medicare beneficiaries with ADRD, our main outcome

Metropolitan Micropolitan Rural

Abbreviation: HCC, hierarchical chronic conditions.

TA B L E 2 Characteristics of Medicare beneficiaries who died between 2008 and 2015

Metropolitan Micropolitan Rural

Abbreviation: HCC, hierarchical chronic conditions.

potentially explain why we saw a spike in ADRD diagnostic incidence

is included as a risk adjustor. closures.

The most perplexing aspect of our findings is that we observed lower

TA B L E A 1 Rurality categories of counties

RUCC 2013 Description Category

Abbreviation: RRUC, rural urban continuum code.

TA B L E A 4 An illustration of how we calculated risk adjusted diagnostic incidence and prevalence

Iteration 0: log likelihood = -9990884.3

Iteration 1: log likelihood = -7959847.3

Iteration 2: log likelihood = -7791967.1

Iteration 3: log likelihood = -7363992.1

Iteration 4: log likelihood = -7346301.1

Iteration 5: log likelihood = -7341857.7

Iteration 6: log likelihood = -7341854.9

Iteration 7: log likelihood = -7341854.9

Multinomial logistic regression Number of obs = 21,446,383

Prob > chi2 = 0.0000

Log likelihood = -7341854.9 Pseudo R2 = 0.2651

Adrd Coef. Std. Err. z P > |z| [95% Conf. Interval]

Age .0875532 .0001844 474.86 0.000 .0871918 .0879146

Hksex .1150767 .0028127 40.91 0.000 .1095638 .1205896

Black .1244485 .0053954 23.07 0.000 .1138736 .1350234

Hispanic −.0981258 .007341 −13.37 0.000 −.1125139 −.0837378

No_CCW_CC .4018247 .0004737 848.32 0.000 .4008964 .4027531

HCC_Community −.1036427 .002543 −40.76 0.000 −.1086269 −.0986586

HHA_Assmnt_PY .0571485 .0012526 45.62 0.000 .0546935 .0596035

Shma −.0984688 .0110809 −8.89 0.000 −.1201869 −.0767507

2 .054408 .0041051 13.25 0.000 .0463622 .0624538

3 .1059648 .0047921 22.11 0.000 .0965726 .1153571

_cons −12.67833 .0158433 −800.23 0.000 −12.70938 −12.64728

Age .1136594 .0001113 1021.18 0.000 .1134412 .1138775

Hksex .1799482 .0017415 103.33 0.000 .1765349 .1833615

Black .1991068 .0032032 62.16 0.000 .1928287 .2053849

Hispanic .0013809 .0041882 0.33 0.742 −.0068278 .0095896

Orace −.1715693 .004912 −34.93 0.000 −.1811965 −.161942

No_CCW_CC .2736333 .0002981 918.06 0.000 .2730491 .2742175

HCC_Community −.1242536 .0015052 −82.55 0.000 −.1272037 −.1213036

Total_NH_Days_PY .0104315 .0000203 514.02 0.000 .0103917 .0104713

HHA_Assmnt_PY .1978542 .0007169 276.00 0.000 .1964492 .1992592

Shma .054728 .0067072 8.16 0.000 .041582 .0678739

Shdual −.1246478 .0089432 −13.94 0.000 −.1421761 −.1071194

2 −.0434924 .0025471 −17.08 0.000 −.0484846 −.0385003

Predictive margins Number of obs = 21,446,383

Model VCE: OIM

1._predict: Pr(adrd = = 0), predict(pr outcome(0))

2._predict: Pr(adrd = = 1), predict(pr outcome(1))