Volume 15, Issue 6
Unisys and DHH Systems Prepare for the Year 2000 Readiness
The arrival of the Holiday Season signifies the end of 1998 and
brings us closer to that inevitable Year 2000.
We have had many providers inquire about the Year 2000 (Y2K)
readiness of both the Department of Health and Hospitals (DHH) and the Unisys
Medicaid Management Information systems (MMIS). The conversion process was
started in 1997 and Unisys continues to work diligently to ensure that all
systems continue to function properly after the millennium change.
New enhancements to the Medicaid system such as the Medicaid
Eligibility Verification System (MEVS) and the Recipient Eligibility
Verification System (REVS) upgrade are Y2K ready. All additional enhancements to
be implemented during the coming year will also be Y2K ready.
Unisys continues to modify existing systems for the millennium
change. While the necessary changes are extensive, Unisys has tried to minimize
changes that would affect you, the provider / submitter. Additionally, with the
pending HCFA changes for standardized electronic submission standards, the
Department of Health and Hospitals and Unisys have elected to maintain current
EMC submission standards until the conversion to HCFA standardized submission,
which has an anticipated implementation date of Fall 2001. Current practices
(those of submitting dates in a six-digit field, MM/DD/YY) will remain in place
and Unisys will employ a windowing technique to expand these dates to an
eight-digit field (MM/DD/CCYY).
While we recognize that this will be different from the planned
Medicare changes, we sought to necessitate as little change as possible with the
forthcoming HCFA standards. By electing to maintain current submission
standards, existing software available in the marketplace should not have to be
modified or replaced; however, you should contact your software vendor to make
sure that your current software will continue to be operable after December 31,
1999. Medicare crossover claims per Medicare specifications will continue to be
accepted from Medicare and will require no changes by you.
Paper claims will continue under existing submission standards
using a six-digit date (MM/DD/YY), which Unisys will expand to eight digits
through a windowing technique. Additionally, Pharmacy Point of Sale submission
practices will not change since the system was implemented Y2K ready.
We hope this will not adversely impact your operations. Should
you have any questions, please feel free to contact Jerry Daugherty at
(225)237-3210. Please watch your future Remittance Advice messages for updates
on the Unisys Y2K conversion project.
Allergen Immunotherapy Codes Clarified
Questions have arisen about a statement made on page 93 of the Professional Services Training manual of 1998. The sentence reads, �For example, a physician may not charge Medicaid or the recipient the cost of allergy serum mixed for the recipient but not administered because the recipient failed to keep the medical appointment.� The answer to the question �To which codes does this statement refer� is as
The CPT Coding Assistant of May 1996 states the allergen immunotherapy codes 95115 and 95117 are for administration of the extract, only.
Codes 95120 through 95134 are to be billed by the prescribing physician for preparing, providing and administering the allergenic extract at a single patient
Code 95144 represents the preparation and provision of extract furnished in a single dose vial(s) by the allergist for administration by another physician. The administering physician reports his/her services with injection codes 95115 and
Codes 95145 through 95170 describe the preparation of the antigen, the antigen extract itself, and the physician�s assessment and determination of the concentration and volume to use, based on the patient�s history and results of previous skin testing. These codes do not include the administration of the
The intent of codes 95145-95165 is to focus on the dose of allergenic extract drawn. It is immaterial whether the dose comes from a series of vials or from a single vial. The code used must describe the
For example, if the patient were to receive a dose of allergenic extract drawn from either a series of vials, each containing a single allergenic extract off a treatment board, or from a single multidose vial, the correct code to use in billing for the service would be
If a physician were to prepare a 10-dose vial for a patient and also administer to the patient one dose in one injection on the same day, the correct codes to use in billing would be 95165 with 10 in the units column and
If the prescribing physician prepares and provides the extract, administers a single stinging insect venom via one injection and administers a separate injection of the venom of two stinging insects, he would bill two codes, 95130 and
A patient is known to be allergic to three different insect venoms (honeybees, hornets, and yellow jackets). The allergist prepares a dosage schedule for treatment, which includes venom for all three of the stinging insects combined into one multiple dose vial containing five doses. The allergist would bill 95147 with 5 in the units column for this
Consequently, the statement on page 93 applies only to codes 95120 through 95134, as all of a code�s components must be rendered before it can be billed.
Notice to Physicians and KIDMED Providers
The Bureau of Health Services Financing announces the funding for the $9.45 administration fee for the Hepatitis A vaccine (code 90730) for children under the age of 21 with the effective date of July 14, 1998.
Global Surgery Periods Assigned to CPT Surgical Codes
Each CPT surgical code has been assigned a global surgery period of either 0, 10, or 90 days. NOTE: On printed material and on the procedure formulary file, codes having a gsp of �0� are shown as having a gsp of �1�. Because �0� is a null value in the Unisys computer system, its use will not activate the gsp edits. In order for the edits to work, a numeral other than �0� has to be used. The numeral selected was �1�. �Ones� in the gsp field on the file are treated in the edits as if they are �zeros�.
Change in Code GO127 Announced
Please be informed code G0127 - Trimming of dystrophic nails, any number - is being made payable to podiatrists for reimbursement on Medicare crossover claims for dates of service 1-1-98 forward. A recycle of claim denials with error edit 210 (provider not certified for this procedure) will be completed shortly. Please do not resubmit these claim denials.Code G0127 is payable for Medicare crossover claims, only.
Increased Fees for Gemzar
The Bureau of Health Services Financing is pleased to announce a fee increase for the chemotherapy drug Gemzar, effective with date of service October 15, 1998. The increased fees are as
J9397 - Gemzar - 200 mg\10ml - $ 76.46
J9398 - Gemzar - 1g\50ml - $382.30
Code 69210 Removed from Global Surgery Edits
As you know, CPT code 69210 - Removal of impacted cerumen (separate procedure), one or both ears - pends for Medical Review and is approved if the diagnosis code is 380.4 (impacted cerumen). Code 69210 is being removed from the global surgery edits. Therefore, if procedure code 69210 is approved by Medical Review, the office visit billed in conjunction with this procedure will be paid. Code 69210 is included in Medicare�s global surgery policy; therefore, all crossover claims for this procedure will continue to be guided by Medicare policy.
Alpha Code Errors Announced
Please be informed the following 1998 Alpha codes were placed in pay status in error. Disbursements for the following codes will be recouped in the near
DME Codes and Prices Change
Recently, two state assigned procedure codes (Z4100 & Z4101) were added to the DME Program for prior authorization and billing for Mickey Gastrostomy tubes. Code Z4100 was added, effective July 1, 1998, with a description of �Mickey Gastrostomy Insertion Kit� and a price maximum of $152.00. Code Z4101 was added, also effective July 1, 1998, with a description of �Mickey Gastrostomy Tube Replacement� and a price maximum of
Please note that BHSF is now revising the description and pricing of these two codes as follows:
The description of code Z4100 is being changed to �Low Profile Gastrostomy Kit w/ Obturator.� The new price maximum will be $192.00. The effective date for this change is December 1, 1998.
The description of code Z4101 is being changed to �Mickey Gastrostomy Kit and Replacement Tube.� The new price maximum will be $114.00. The effective date is also December 1,
Additionally, please note that BHSF is adding the following code to the DME Program for the prior authorization and billing of the Percutaneous Endoscopic Gastrostomy (PEG) tubes:
Procedure code Z1402 is being established, effective December 1, 1998, with a description of �PEG type Gastrostomy tube.� The price maximum established is
Other existing codes for gastrostomy and naso-gastric feeding tubes are:
- B4081 - Naso Tube w/ Stylet (price max = $15.82)
- B4082 - Naso Tube w/out Stylet (price max = $11.78)
- B4083 - Stomach (Levine) Tube (price max = $1.80)
- B4084 - Gastrostomy/ Jejunostomy Tube (price max = $13.21)
The following related supply items may be requested and billed using procedure code B9998 (�Miscellaneous Enteral Supplies�):
- Decompression Tubes (price max = $16.00)
- Extension Tubing (G-Tube Adaptor) (price max = $ 9.38)
- Secur-Lok Extension Set (price max = $ 15.00)
- Bolus Feeding Set (price max = $15.00)
DHH Accepting Nominations for Drug Utilization Committee
The Department of Health and Hospitals is currently accepting physician and pharmacist nominations for the Region 3 Drug Utilization Committee. The committee consists of three pharmacists and one physician who meet monthly to review profiles of drug usage from a therapeutic perspective and to clarify or send information to the medical community. Currently, one physician opening and one pharmacist opening are available. We are requesting that the nominees be Louisiana Medicaid providers and practice in at least one of the following
Prospective committee members must have time available to meet monthly for one to three hours and must meet the following
- Doctor of medicine degree from an accredited U.S. medical school
- Licensed to practice in Louisiana as a medical doctor
- Board certification in their specialty
- No previous sanctions from the State of Louisiana
- Pharmacy degree from an accredited U.S. pharmacy school
- Licensed to practice in Louisiana as a pharmacist
- No previous sanctions from the State of Louisiana
Please print or type your nomination on the form in the space provided below and return the form as soon as possible
Unisys Louisiana Medicaid
8591 United Plaza Blvd., Suite 300
Baton Rouge, LA 70809
ATTN: S. Delaville
LMMIS REGION THREE DRUG UTILIZATION REVIEW COMMITTEENAME:________________ PHONE:_____________________ ADDRESS:___________________________________________ _________________________________________ PARISH:_______________ EMPLOYER:_________________
I am nominating the above mentioned for consideration as a member in the LMMIS REGION THREE DRUG UTILIZATION REVIEW
DHH Accepting Nominations for State Drug Utilization Review
The Department of Health and Hospitals is currently accepting pharmacist nominations for the State Drug Utilization Review Board. The DUR Board is an advisory board that meets quarterly in Baton Rouge and fulfills these functions:
- Application of standards
- Retrospective drug utilization review
- On-going interventions with pharmacists and physicians concerning therapy problems identified in the course of retrospective drug utilization reviews
- Publishing an annual report
One pharmacist opening is currently available. We are requesting that the nominee be a Louisiana Medicaid provider and meet the following requirements:
- Pharmacy degree from an accredited U.S. Pharmacy school
- Licensed to practice in Louisiana as a pharmacist
- No previous sanctions from the State of Louisiana
Please print or type your nomination on this form in the space provided below and return the form as soon as possible
Unisys: Louisiana Medicaid
8591 United Plaza Blvd., Suite 300
Baton Rouge, La. 70809
ATTN: S. Delaville
STATE DRUG UTILIZATION REVIEW BOARD
NAME:________________PHONE:_____________________ ADDRESS:_________________________________________ _________________________________________ PARISH:_______________ EMPLOYER:_________________
I am nominating the above mentioned for consideration as a member in the LMMIS STATE DRUG UTILIZATION REVIEW
Usual and Customary Charges
Can Cause DiscrepancyPostlethwaite and Netterville, our contracted agent for conducting pharmacy audits, has completed the second year of audits. A discrepancy that has frequently occurred involves usual and customary charges. We would like to reiterate our policy to assure compliance with federal and state
Federal regulations governing the Medicaid Program require that participating providers agree to charge no more for services to eligible recipients than they charge for similar services to non- recipients (general public). In implementing this regulation, the Medicaid Program states that providers in the Pharmacy Program may not charge a higher dispensing fee, on the average, for recipients� prescriptions than is charged for non-recipients� prescriptions (third party and insurance prescriptions are components of the non-recipient
In performing the pricing portion of the audit, there are certain criteria utilized to establish whether a pharmacy is overcharging the Medicaid program. Some of these criteria include the following: making sure the prescription is not for catheters, catheterization trays, insulin, or diabetic supplies. (These are audited
Thus, we would like to remind pharmacists that if generic prescriptions are to be included in the general public sample of the pricing audit, then the manufacturer or labeler of the drug must be identified on the hard copy prescription or the computerized prescription file. Also, pharmacists should indicate their usual and customary charge on their claims when billing for prescription services, even if this charge exceeds our maximum payment.
CPT Code 78315 Announced
The Bureau of Health Services Financing is pleased to announce the funding of CPT code 78315 - Bone and/or joint imaging; three phase study, effective with date of service December 1, 1998, at a full service fee of $170.84. The professional component fee is $68.34.
Prescription Payment Responsibility of Skilled Nursing
When a resident of a skilled nursing facility is in Medicare payment status, payment for prescription medications becomes the responsibility of the facility as prescription services are included in the per diem paid by Medicare. When the facility is paying for the medications, the facility has a right to contract with a pharmacy of its choice. If the resident converts back to Medicaid, at that point the resident may exercise his right to utilize the pharmacy of his
A skilled nursing facility may choose to contract with whomever it wishes in order to obtain medications for the Medicare
When Medicare is the primary and Medicaid is the secondary payor for a resident, Medicare regulations govern the reimbursement. The same holds true for Medicare as the primary with no Medicaid as the secondary.
New Codes for CNPs
Effective with date of service October 1, 1998 the following codes are being added to the list of codes reimbursable to Certified Nurse
Certified Nurse Practitioner services are reimbursed at 80% of the current fee on file, with the exception of immunizations, which are reimbursed at 100% of the fee on file.
Pharmacy Compliance Audit Findings
Reference: Chapter 16, Medicaid of Louisiana
Page 10-2, Reissued February 1, 1993
Both State and Federal Regulations certify that the MAC limits for drugs do not apply if �A physician certified in his own handwriting, in his medical judgement, a specific brand is medically necessary for a particular medication for a particular recipient�. The wording of the certification must testify to the medical necessity of the brand name drug either �Brand Medically Necessary�: or �Brand Necessary�. Dispense as written� or Do not substitute� are not acceptable for overriding MAC limitations. Again, the certification must be in the physician�s
Please note: To prevent a change from the brand name product to a generic product on a Medicaid prescription, the physician must make a notation �Brand Medically Necessary� in his own handwriting for each prescription written on the face of the prescription. If two or more prescriptions are written on the same prescription pad and the physician indicates that the Brand name product is necessary for more than one of the medications, he must write �Brand Medically Necessary� for each medication. It is suggested that a drug which the physician testifies to have the medically necessity of Brand name for a particular recipient should be listed individually on a
Please note: The intent of the Federal and State regulations regarding Maximum Allowable Costs is to allow for a specific brand of medication when it is deemed to be of medical necessity, and to prevent practices which result in unnecessary costs to the Medicaid program or in reimbursement for services that are not medically necessary or that fail to meet professionally recognized standards for health care.
Reference: Chapter 16, Medicaid Services Manual
Page 5-6, Reissued February 1, 1993
Please be advised that Nicotine transdermal patches and Nicotine polacrilex gum are covered only with a handwritten prescription signed by the prescribing practitioner - an original prescription only - with no provisions for refills. The physician will need to rewrite a prescription each time. Also, physicians must certify, in their own handwriting, either directly on the prescription or on an attachment to the prescription, that the recipient is enrolled in a physician-supervised behavioral program in order for Medicaid to provide coverage for Nicotine adhesive patches. Providers should verify that the above noted documentation is included on the prescription.
Reference: Chapter 16, Medicaid of Louisiana
Page 5-6, Reissued February 1, 1993
Please be advised, Isotretenoin capsules (10 mg, 20 mg, and 40 mg) will be covered only if a handwritten prescription signed by the prescribing practitioner is submitted, with no provisions for refills.
Reference: Chapter 16, Medicaid Services Manual
Page 5-1, 5-2, Reissued February 1, 1993
Please be advised that all prescriptions must be signed by a licensed practitioner. In cases where a prescription is from a Charity Hospital and the physician�s name is difficult to read, an original prescription must be on file. All telephone prescriptions from Charity Hospitals should clearly identify the prescriber who authorized the prescription. When updating an original hard copy prescription, be sure to identify the physician authorizing the new prescription. You should bill using the prescribing physician�s provider number and not the institution�s number in as many instances as possible.
Reference: Chapter 16, Medicaid Services Manual
Page 10-1, Reissued February 1, 1993
Louisiana Medicaid Provider UpdateVolume 13, Number 2 (March/April 1996)
All providers of medical services are required by Federal regulations to charge no more for services provided than is charged to the general public. Consequently, pharmacists are required to indicate their usual and customary charge on their claim forms for prescription
Specifically, Federal regulations governing Medicaid of Louisiana require that participating providers agree to charge no more for services to eligible recipients than they charge for similar services to non-recipients (the general public). In addition, in implementing this regulation, Medicaid of Louisiana states that providers in the pharmacy program may not charge a higher dispensing fee, on the average, for recipients� prescriptions than is charged for non-recipients prescriptions. These non-recipient prescriptions include all third-party prescriptions, all other insurance prescriptions, and cash customer prescriptions. Therefore, all prescriptions filled for patients other than Medicaid recipients are included in general public prescriptions.
DRUG UTILIZATION REVIEW (DURS)
ESTIMATED DAYS SUPPLY
It has come to our attention that some claims are being submitted with incorrect estimated days supply information. We are aware that some computer systems or policies automatically default to a predetermined value. Please remember to individualize each entry using your best professional judgement and to carefully consider your input. Incorrect estimations will result in incorrect identification of overutilization and underutilization parameters which are used to provide important clinical data. Your attention to this detail is appreciated.
Correct Taxpayer ID Information for All Providers
As we approach the end of another year, the Bureau is reminding all providers once again of their responsibility to report any changes in Taxpayer Identification Number (TIN), also known as Employer Identification Number (EIN), to the Provider Enrollment Unit. If you submitted a Form SS-4 to the Internal Revenue Service for a new number in 1998 and obtained a new number, please mail or fax a copy of your Notice of New Employer Identification Number Assigned to the Provider Enrollment Unit. In a letter or on the fax cover sheet, please list the Medicaid provider numbers affected by any changes.
Bureau of Health Services Financing
P. O. Box 91030
Baton Rouge, LA 70821-9030
Attention: Provider Enrollment Unit
FAX Number: (225) 342-3893
We are asking that you act upon this immediately in order for the forms 1099 which will be issued the latter part of January 1999 to include the correct identification number.
New Local Phone Number for REVS
A new, local telephone number has been added to the Recipient Eligibility Verification System (REVS) for local provider use. The new number is 216-REVS (7387). If you are located in the Baton Rouge area, please begin using this number rather than (800) 776-6323. This will allow more long distance providers accessing REVS to use the toll free number for eligibility verification. We hope this new number will be a positive and effective addition for your
REVS Reminders: Please remember to use eight-digit numbers (dates of birth, dates of service, etc.) when accessing information using REVS. Also, please remember if you are using a 13 digit recipient number to access REVS, only recipient identification numbers which are current within the last 12 months will allow you to access REVS eligibility information. If you are using a number that is not valid within the last 12 months, the system will respond stating the recipient is not on file.
LONG TERM CARE COMPLAINTS
The Health Standards Section toll free phone line for Long Term Care complaints is now active. The toll free number is
LONG TERM CARE REPORTS OF ABUSE/NEGLECT NOTIFICATION
When a LTC Facility (Nursing homes or ICF/MR) notifies the Health Standards Section of a report of abuse or neglect, or sends in a completed investigation/report, address this correspondence to: Report of Abuse/Neglect Program Desk, P.O. Box 3767, Baton Rouge, LA 70821 or FAX to (225)
HEALTH STANDARDS FAX LINE:
The Health Standards Section FAX number was temporarily changed during the summer due to moving to a new location (655 North Fifth Street-Third Floor). The original fax number was reinstated in late September. Please make note that our FAX number is (225) 342-5292.
Electronic Claims Submission
Electronic media claim submission is an alternate method of submitting Medicaid claims to Unisys. With electronic media, a provider or a third party contractor (billing agent) submits Medicaid claims to Unisys on a computer encoded magnetic tape, diskette or via
Each claim undergoes the editing common to all claims, e.g., verification of dates and balancing. Each type of claim has unique edits consistent with the requirements outlined in the provider manuals. All claims received via electronic media must satisfy the criteria listed in the manual for that type of
Advantages of submitting claims electronically include increased cash flow, improved claim control, decrease in time for receipt of payment, automation of receivables information, improved claim reporting by observation of errors and reduction of errors through pre-editing claims
Each reel of tape, diskette or telecommunicated file submitted for processing must be accompanied by a submission certification form signed by the authorized Medicaid provider or billing agent for each provider whose claims are billed using electronic media. The certification must be included in each tape or diskette submitted. Providers submitting by telecommunications must submit this certification within 48
If you are not in possession of the certification forms, you should call the EMC Department at Unisys and request an EMC packet. The packet includes all the different types of certification forms required. Third-party billers are also required to submit a certification form. You should select the certification form in the packet that applies to your particular provider type and make copies as necessary for submission to Unisys. Contact the EMC Department at Unisys at (225) 237-3303. The mailing address for the EMC Department at Unisys is P.O. Box 91025, Baton Rouge, LA 70821.
Guidelines for Timely Filing
In order to be reimbursed for services rendered, all providers must comply with the following filing limits set by Medicaid of Louisiana:
- Straight Medicaid claims must be filed within 12 months of the date of service.
- Claims for recipients who have Medicare and Medicaid coverage must be filed with the Medicare fiscal intermediary within 12 months of the date of service in order to meet Medicaid�s timely filing regulation.
- Claims that fail to cross over via tape and have to be filed hardcopy may be filed up to six months after the date on the Explanation of Medicare Benefits (EOMB), provided they were filed with Medicaid within a year of the date of service.
- Claims with third -party payment must be filed within 12 months of the date of service.
- Claims for recipients with retroactive coverage, e.g., spend-down medically needy claims, should be sent to Unisys with a note of explanation or a copy of the recipient�s Medicaid identification card as soon as possible. The mailing address for Unisys is as
P.O. Box 91024
Baton Rouge, LA. 70821
All claims for recipients with retoactive medical coverage will be forwarded to the BHSF for review and authorization.
CommunityCARE Claims Corrected
During the time period from May through October of 1998, certain claims filed with a place of service of inpatient hospital, outpatient hospital, or ambulatory surgical center were paid in error. Due to a systems error, these claims were not subject to the edit (EOB 106) which requires that the correct referral number for a CommunityCARE recipient�s Primary Care Physician be entered on the claim form. All pertinent claims have been recycled, and any paid in error appeared as voided claims on Remittance Advices dated October 27, 1998. Voided claims may be refiled with referral authorization numbers for the CommunityCARE PCP. If you have questions regarding this matter, please contact Unysis provider Relations at 800 473-2783 or 225 924-5040
Act 1142 Extends Program Material Life
Act 1142 passed by the 1997 Legislature increased the length of time a provider must maintain program-related material from three years to five years.
Increased Fees for Depo- Provera
The Bureau of Health Services Financing is pleased to announce a fee increase for Depo-Provera for contraceptive use, code J1055, effective with date of service October 15, 1998. The increased fee is $43.05.
CPT Code 83019 Returned to Pay Status
Recently you were notified that CPT code 83019 - Helicobacter pylori, breath test (including drug and breath sample collection kit) was being placed in nonpay status effective with date of service July 1, 1998. This test was considered by Medicare to be investigational.
Due to a revision in Medicare�s policy, as stated in the September, 1998 issue of the Louisiana Part B - Medicare Providers� News, we are placing this code in pay status effective with date of service September 15, 1998. The 62% fee for code 83019 is $41.33. The 60% fee is $40.00.
CPT Code 87799 Priced Individually
Please be informed claims for CPT code 87799 - Infectious agent detection by nucleic acid (DNA or RNA); not otherwise specified, quantification - are individually considered for pricing. Claims are to be submitted hardcopy with documentation including a description of the test performed and its methodology attached. Claims submitted electronically, or without attached documentation, will be denied.
LADUR Educational Article
Alzheimer�s Disease:Diagnosis and Treatment
By C. David Matthews, Pharm.D., Doris L. Matthews, R.N., J. Lance Nickelson, Pharm.D., and Edwin H. Adams, Pharm.D.
ISSUES . . . -
The number of Americans suffering from Alzheimer�s Disease is expected to triple in the next 50 years.
The risk of Alzheimer�s Disease increases with age, with the incidence doubling every 5.1 years after age 40.
Alzheimer�s Disease is the third most expensive disease in the U.S. behind heart disease and cancer. effective cost
Alzheimer�s Disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the industrialized world. It is one of the most prevalent illnesses among the elderly, and with an aging population, AD will become an even greater problem in most industrialized countries. The disorder usually begins gradually, causing a person to forget recent events or familiar tasks. How rapidly AD advances varies from person to person, but the degenerative disease eventually causes confusion, personality and behavior changes, and impaired judgment. Communication is increasingly difficult as the affected person struggles to find words, finish thoughts or follow directions. Most people with Alzheimer�s disease eventually become unable to care for themselves. With disease progression, patients may experience psychiatric and behavioral disturbances and always suffer progressive loss of the ability to perform activities of daily living (ADL). When the deterioration of the patient causes several ADLs to be lost, the AD patient may eventually be placed in a nursing home.
Alzheimer�s disease affects approximately 4 million Americans in the United States alone, a figure that is expected to triple over the next 50 years as the elderly population grows. One in 10 patients over 65 and nearly half of those over 85 have Alzheimer�s disease. Fourteen million Americans will have AD by the middle of the next century unless a cure or prevention is found. The risk of AD increases with age, with the incidence doubling every 5.1 years after age 40.
A person with Alzheimer�s disease lives an average of 8 years, and a few live as many as 20 years or more, from the onset of symptoms. U.S. society spends at least $100 billion a year on Alzheimer�s disease. Neither Medicare nor private health insurance covers the type of long term care most patients need. More than 7 of 10 people with Alzheimer�s disease live at home. Almost 75 percent of the home care is provided by family and friends. The remainder is �paid� care costing an average of $12,500 per year, most of which is covered by families.
Half of all nursing home patients suffer from Alzheimer�s or a related disorder. In 1991, the discounted direct cost average per patient for nursing home care was $47,000 per year, but exceeded $70,000 per year in some areas of the country. The average lifetime cost per patient is estimated to be $174,000, making Alzheimer�s disease the third most expensive disease in the United States, trailing only heart disease and cancer.
ETIOLOGY & DISEASE PROGRESSION OF AD
Scientists are still not certain of the exact etiology of Alzheimer�s disease. Age and family history have been identified as potential risk factors. Alzheimer�s disease causes the formation of abnormal structures in the brain called plaques and tangles. As they accumulate in affected individuals, nerve cell connections are reduced. Areas of the brain that influence short-term memory tend to be affected first. Later, the disease advances to areas that control other intellectual and physical functions.
Alzheimer�s disease affects people in different ways, making it difficult for medical professionals to predict how an individual�s disease will progress. Some experts classify the disease by stage (early, middle and late). Specific behaviors and the duration of them vary greatly among patients, even within each stage of the
AD is diagnosed conclusively only by an autopsy after death. Its telltale signs during life, suchas dementia symptoms, also may be caused by other problems. To confirm AD, pathologists look for the presence of characteristic plaques and tangles in brain tissue during an autopsy. Through the work of many researchers, the diagnosis of AD in living people has become more and more accurate. In specialized research facilities, neurologists now can diagnose AD with up to 90 percent accuracy, as confirmed later at autopsy. As more is learned about the progression of the disease, new assessment scales are being developed to help physicians track, predict, and treat symptoms of Alzheimer�s. In keeping with FDA-defined dual-outcome criteria for clinical trials in AD patients, both a cognitive performance scale and a global-function assessment scale are used to evaluate the efficacy of treatment. Two scales have been accepted by the FDA as measures of the efficacy of AD treatments: the Alzheimers�s Disease Assessment Scale-Cognitive Portion (ADAS-cog) and the Clinician�s Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus).
The Mini-Mental State Examination (MMSE) is a 30 point standardized test that evaluates the patient�s mental status. It includes questions that evaluate orientation, attention, short-term and intermediate-term recall, language, and the ability to follow simple oral and written commands. Lower scores indicate greater cognitive impairment.
In the mid 1970�s, scientists discovered that levels of a neurotransmitter called acetylcholine fell sharply in people with Alzheimer�s disease. The discovery was intriguing for several reasons. Acetylcholine is a critical neurotransmitter in the process of forming memories. Moreover, it is the neurotransmitter used commonly by neurons in the hippocampus and cerebral cortex�regions devastated by Alzheimer�s disease.
Since that early discovery, one of the first to link Alzheimer�s disease with biochemical changes in the brain, acetylcholine has been the focus of hundreds of studies. Scientists have found that ACh levels fall somewhat in normal aging, but drop by 90 percent in people with Alzheimer�s disease. There is evidence linking this decline to memory impairment. Treatment has centered upon methods to boost ACh levels to arrest progression of the disease.
The current treatment of Alzheimer�s disease is somewhat analogous to the way Parkinson�s disease was treated 25 years ago, before the availability of levodopa. Immediate goals in treating and managing the dementia symptoms of AD are to slow, reduce, and/or reverse its mental and behavioral signs. The eventual goal is to stop the disease process altogether. Scientists are pursuing many leads to accomplish these goals, but the current focus is on the patient�s symptoms and unusual behaviors. Several clinical trials are testing a variety of compounds to evaluate effectiveness. Scientists are looking for treatments that work on many patients, stay effective for a long time, ease a broad range of symptoms, improve patients� activities of daily living and cognitive function, and have no serious side effects.
In 1996, the Food and Drug Administration (FDA) approved donepezil hydrochloride (Aricept�) to help treat some mild to moderate symptoms of AD. Aricept� was the second drug approved by the FDA to treat AD. The first drug, Cognex� (tacrine), has been marketed since 1993. These agents confirm the �cholinergic deficency hypothesis,� which holds that AD is caused by the loss of cholinergic neuronal function. Both drugs are classified as acetylcholine esterase inhibitors (AChEI) which inhibit the breakdown of Acetylcholine by the enzyme. Unfortunately, neither drug stops nor reverses the progression of AD. Occasional side effects of Aricept include diarrhea and nausea. The drug also can cause an irregular heartbeat, especially in patients with heart conditions. Fainting spells have been reported in some patients. However, Aricept� seems not to affect liver enzymes, an effect that prevented many patients from taking Cognex�. Most researchers agree that neither Aricept� nor Cognex� works for all, or even most, patients so that the drugs� effects and duration of usefulness are limited. These drugs only temporarily halt or reverse cognitive losses from AD, and do not prevent AD from continuing to kill the nerve cells that normally produce acetylcholine.
The search for more effective ways to treat and prevent AD includes studying the use of estrogen, anti-inflammatory drugs, and other compounds in AD patients; determining which groups of people develop AD; and conducting several initiatives related to caregiving. Recent findings in a study by Grant indicate that elderly African-Americans and Japanese living in the United States have a much higher prevalence of Alzheimer�s disease (6.24% and 4.1%, respectively) than those still living in their ethnic homelands (<2%) suggested that environmental rather than genetic factors are the primary agents causing Alzheimer�s disease. Recent papers linking clinical expression of Alzheimer�s disease to oxidative stress and cerebral infarct suggest that diet may be a key factor in the development of Alzheimer�s disease. The primary findings are that fat and total caloric supply have the highest correlation with Alzheimer�s disease. In addition, fish consumption is found to reduce the prevalence of Alzheimer�s disease in the European and North American countries. The literature suggests that fat contributes to oxidative stress and inflammation and that fish oils combat inflammation. Recent papers finding that several dietary components and supplements have been found effective in delaying the onset of Alzheimer�s disease, including antioxidants, fish and fish oils, and non-steroidal anti-inflammatory drugs (NSAIDs) are consistent with this
USE OF SELEGINE AND VITAMIN E
Oxidative changes are seen in the brains of AD patients. Studies of compounds that fight oxidation put researchers one step closer to understanding processes that damage cells and finding ways to treat, and possibly prevent AD. The NIA-supported ADCS trial of selegiline (l-deprenyl or Eldepryl�) and alpha-tocopherol (vitamin E) is one such study.
Both selegiline and vitamin E act as anti-oxidants. Selegiline, which has been used to treat patients with Parkinson�s disease, works by inhibiting an enzyme in the brain that impairs certain neurotransmitter systems. For 2 years, researchers studied 341 moderately impaired patients with probable AD who were recruited from 23 centers taking part in the ADCS. Participants were divided into four groups that received different treatments: selegiline, vitamin E, both selegiline and vitamin E, or a placebo. Overall, this study shows that treatment with selegiline or vitamin E reduced moderately impaired AD patients� risk of reaching one of the four primary outcomes, with an estimated average delay of 6.5 months. In addition, these findings support the idea that damage due to oxidation plays a role in AD.
Scientists caution that further research is needed to confirm these preliminary findings. Researchers need to find out if these types of drugs actually can delay the development of symptoms much earlier in the course of the disease and learn how these drugs might affect patients at different stages of AD. Investigators further warn that selegiline may have potential side effects and interactions with other drugs. In addition, the dosage of vitamin E used in this study was much higher than that typically found in daily supplements. Vitamin E may be associated with an increased risk of bleeding in some people. Although both selegiline and vitamin E showed efficacy when used alone, when used together their benefit was less than either agent used alone, in other words, there was no synergy between agents.
ESTROGEN REPLACEMENT THERAPY
Estrogen replacement therapy (ERT) was associated with a reduced incidence of AD in a group of older women. This 5-year investigation was unique because all of the women were examined and interviewed about their estrogen use before they developed AD symptoms; and it was the first AD study group with similar numbers of older women of African American, European, and Hispanic American ancestry. Previous studies depended on the review of death certificates and patients� and/or caregivers� memories of using estrogen. The estimated annual incidence rate for AD among women in the study who took estrogen was 2.7 percent, compared to 8.4 percent among those who did not take estrogen.
These results suggest that estrogen use during and after menopause may significantly lower therisk of AD and delay the onset of AD symptoms. The duration of estrogen use also seemed important in reducing risk. Women with a history of long-term use (more than 10 years) had the lowest risk. But, even women who took estrogen for a short time and then stopped also benefitted. From this study, researchers conclude, for example, that a woman who takes estrogen for 10 years at, and after, menopause may reduce her risk of developing AD by 30 to 40 percent, compared to other women her age.
While these findings are encouraging, clinical trials are needed before doctors can recommendestrogen to women for delaying or preventing AD. Clinical trials will determine whether estrogen therapy can delay or prevent the onset of AD as well as the safety, dose, and duration of estrogen treatment needed to produce these effects. One such clinical trial, the Alzheimer�s Disease Cooperative Study (ADCS) trial of estrogen, is assessing the effect of ERT on the progression of AD in postmenopausal women who have the disease.
The tremendous amount of research and recent clinical progress in our understanding of this disease bodes well for new treatment developments in the future. In a very few years at the current pace of research and pharmacological agent development, the medical community should have agents that prevent and slow the spread of this debilitating disease.
Aricept package insert. New York : Roerig, Division of Pfizer, Inc.;
Ernst RL, Hay JW, Max W et al. The economic burden of Alzheimer�s disease care. AM J Public Health ,
Grant, WB, Dietary Links to Alzheimer�s Disease, Alzheimer�s Disease Review 2, 1997:42-45.Jann, MW. Pharmacology and clinical efficacy of cholinesterase inhibitors. Am J Health-Syst Pharm. 1998; 55 (Suppl
Jenkins on ML, Bliss MR, Brain AT et al. Rheumatoid arthritis and senile dementia of the Alzheimer�s type. Br J Rheumatolo. 1989;28:86-8
Lerner A, Koss E, Debanne S et al. Smoking and estrogen replacement therapy as protective factors for Alzheimer�s disease. Lancet. 1997;349:403-404
Parnetti, L, Senin U, Mecocci P. Cognitive enhancement therapy for Alzheimer�s disease: the way forward. Drugs, 1997:53:752-
Ranks AS, Rawls WN. Alzheimer�s Disease: clinical features and pharmacologic management. Am J Manag Care. 1998;4:595-
Rice DP, Fox PJ, Max W et al. The economic burden of Alzheimer�s disease care. Health Aff.
Rich JB, Rasmusson DX, Folstein MF et al. Nonsteroidal anti-inflammatory drugs in Alzheimer�s disease. Neurology. 1995;
Sano M, Ernesto C, Thomas RG et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer�s disease. N Engl J Med. 1997;
Schumock, Glen T. Economic considerations in the treatment and management of Alzheimer�s disease. Am J Health-Syst Pharm. 1998; 55 (Suppl 2):
Simonson, W. Promising agents for treating Alzheimer�s disease Am J Health-Syst Pharm. 1998; 55 (Suppl 2):S11-6.