Brain Injury & Phineas Gage

Sep
14

On this date in 1848, railway employee Phineas Gage survived having an iron rod pushed through his brain. He was twenty-five years old, a good looking young guy and a hard worker, and was a foreman on a team cutting a railroad bed in the vicinity of Cavendish, Vermont. He was using a tamping iron to pack explosives into a hole in a boulder when the volatile powder detonated. It drove his tamping iron — which was 43 inches long, and an inch and one fourth wide — through his left cheek, up behind his left eye, and out the top of his head, where it landed some thirty yards away. He lost the vision in his left eye, but it’s feasible that he didn’t even lose consciousness; in any event, he was in a position to wander to an oxcart within a couple of minutes of the incident. Workers took him to his boarding house, where he had enough of his wits about him to quip to the local doctor, “Here is business enough for you. ” One witness reported that Gage got up and vomited; “the efforts of vomiting pushed out about half a teacupful of the brain, which dropped upon the floor. ”

The physician, John Martin Harlow, cleansed the injuries, removed the smaller sized bone fragments and supplanted a few bigger ones. He closed the top head wound with adhesive, but kept it open to drain into the dressing. Gage hit a couple of stumbling blocks in the following weeks, developing what the doctor called a “fungus” on an exposed segment of his brain, which placed him in a semi-comatose state and prompted his family members to purchase a coffin for him. He additionally developed an abscess below the scalp, which the doctor drained before it could leak into his brain cavity. But by the next January, Gage had completely recovered, even though the significant exit wound never fully healed.

Even though he was living a seemingly normal life, Gage’s associates observed remarkable changes in his character in the weeks after the episode. Dr. Harlow faithfully recorded them and shared them 20 years later in the Bulletin of the Massachusetts Medical Society: “He is fitful, irreverent, indulging at moments in the grossest profanity (which was not recently his custom), manifesting but little deference for his fellows, impatient of restraint of advice when it conflicts with his wants, at times pertinaciously obstinent [sic], yet capricious and vacillating, devising many strategies of future operations, which are no sooner arranged than they are forgotten in turn for others appearing more achievable. In this respect, his mind was radically changed, so highly that his associates and colleagues said he was ‘no longer Gage. ‘” He lost his job with the railway business and took work in stables, driving coaches, until he passed away 12 years afterwards following a string of seizures.

Had he merely lived through the incident with the majority of his faculties intact, he would have gone down in history as an oddity. As it turned out, he also inspired new areas of brain analysis and became one of the most famous individuals in neuroscience. Even though there wasn’t much hard data recorded about Gage, researchers began looking into a connection between brain damage and personality change. They also became engaged in “mapping” the mind, identifying a link in Gage’s scenario between the frontal cortex and societal inhibitions, and positing that different regions of the brain may manage various capabilities. Two-thirds of psychology textbooks refer to him. His skull and the tamping iron are on display at the Warren Anatomical Museum at Harvard’s School of Medicine.

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Poststroke Dementia

Dec
28

A range of studies have confirmed a prominent incidence of cognitive impairment and dementia after stroke with rates ranging from 6 to 32 percent in patients observed from three months to 20 years. Transitority assessments (<1 year) are probable to considerably over-diagnose post-stroke dementia. In one study that used a control unit, stroke was associated with a 3.83 relative risk (RR) for dementia compared with nonstroke hospitalized controls.

Populace-centered studies have observed somewhat conflicting results regarding the likelihood of dementia following stroke. A collective diagnosis that integrated both population-based and hospital-based cohorts determined that 10 percent of patients with a first stroke had pre-stroke dementia and 10 percent subsequently presented dementia, while more than one-third of patients developed dementia after a recurrent stroke. Mild cognitive impairment before stroke raises the likelihood of post-stroke dementia. In another meta-diagnosis, a stroke background was observed to confer a 2 -fold increased risk of dementia in patients younger than, but not older than 85 years.

Age is nearly uniformly determined to elevate the risk of dementia following stroke. Other risk factors frequently, but not uniformly, acknowledged in this environment include increased severity of the index stroke, atrial fibrillation, the presence of white matter ailment and cortical atrophy on imaging, multiple medical circumstances or lesions on neuroimaging, hypertension, obesity, elevated homocysteine or high density lipoprotein levels, and diabetes mellitus. A number of reviews point out that stroke in the left hemisphere, particularly the ones with associated aphasia, is a risk factor. Confirmation of premorbid cognitive harm is also a risk element, whereas higher educational level favorably modifies the possibility for post-stroke cognitive decline. In fact, one study determined that mild cognitive impairment was a prerequisite for incident dementia after stroke. Most studies have not recognized gender as a risk factor, but two observed a greater incidence in females and one in males.

While some analyses indicate that most conditions amass early after stroke, some others have demonstrated fairly steady accrual of conditions over years of yearly test evaluations. This is complicated by the actuality that cognitive status after stroke is unstable; comparisons among three-month and one-year assessments reveal that though certain patients worsen, some improve, and in a few cases the incidence of dementia is in reality much less at one year than it is at three months. Within one cohort study, chronic stroke was linked with elevated cognitive decline compared with patients with a single stroke. Most studies did not establish cases as AD or VaD; in the ones that did, VaD rather than AD was the prognosis in lots of cases (51 to 66.7 percent).

Data from the Nationwide Long-Term Care Evaluation suggest that post-stroke dementia is an ever-increasing problem, with age-uniform rates growing from 0.043 between 1984 to 1990 to 0.080 between 1991 to 2001. A concomitant decline in stroke case-fatality rates was also acknowledged, which could add to the higher proportion of dementia. Cognitive impairment subsequent to stroke is additionally an influential contributor to nursing home placement and shortens survival.

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Alzheimer’s is Not Waiting Part I: Screening

Dec
27

Advanced Edition
Leo J. Borrell, M.D.
President & Senior Medical Consultant

Our Mission
It is our pledge to provide compassionate service, care, and treatment for the emotional,  social and physical well-being of the elderly, their family and caregivers.

Our Goal
Our goal is to allow seniors to retain the highest possible level of comfort and cognitive  ability while maintaining their quality of life.

Because 50-90% of patients are undiagnosed with dementia and other brain or psychiatric problems that lead to behavior problems they are under treated or over treated. This often results in difficulties with Medicare surveyors with the consequences of F501, F329, F330 and F429 tags. Senior PsychCare, in cooperation with nursing staff, has developed a progress to conduct initial screening s on all patients. We utilize objective tests to evaluate the neurocognitive status of patients and cover a range of mental processes, such as motor performance, attention, and memory if there is suspicion of a problem. We ten have professionals so neurobehavioral evaluations and if indicated a more comprehensive computer assessment called BCNI (Borrell Cognitive Neuropsychiatric Inventory) is conducted. This assessment allows to:

• Establish and document current status and use in later treatment decisions
• This distinguishes early mild or subtle behavioral problems in patients through comparison to other individuals his/her age
• This leads to decision making on the course of action to take. Counseling, medications, and social treatments to maintain quality of life are provided.
• It helps families understand the problem that effect emotion and behavior. Also it allows making a
prediction of the future functions, emotional, and social needs to improve the quality of life.

Senior PsychCare will make best efforts to use the evaluation to direct treatment in collaboration with the family, facility, staff and primary care physician.

More information about the screening process is available by contacting Tammy Simon, FIR Director at SPC, at 713 850 0049. Based on the fact that we are committed to providing the best and available care, we are providing there services under the professional staff of your long-term health care center. Thus we comply and are compliant with all HIPAA regulations.

Thank you for your time and patience.

The Utility of Mandatory Depression Screening of Dementia Patients in Nursing Homes

Carl I. Cohen, M.D.
Kathryn Hyland, Ph.D.
David Kimhy, M.D.

Depression in Assisted Living is Common and Related to Physical Burden

Lea C. Watson, M.D., M.P.H., Susan Lehmann, M.D.,
Lawrence Mayer, M.D., PhD., Quincy Samus, M.S.,
Alva Baker, M.D., Jason Brandt, Ph.D.,
Cynthia Steele; R.N.,M.P.H., Peter Rabins,
Adam Rosenblatt, M.D., Constantine Lyketsos, M.D., M.H.S.

In the first clinical study implemented by geriatric psychiatry professionals in AL, depression was found to be common, under treated and related to physical burden. AK is a rapidly growing segment of long-term care and represents an important setting in which to find and treat serious depression. (Am J Geriatric Psychiatry 2006; 14:876-883)

Why Screening is Indicated on all Ltc. Residents for Depression and Dementia
Neuropsychological testing in Skilled Nursing Facilities: The Failure to Confirm Diagnoses of Dementia

Irwin J. Mansdorf, Ph.D., Mary Harrington, LCSW, Jacqueline Lund, LCSW, and Nancy Wohl, LCSW

Dementia diagnoses may be inaccurate for 90% nursing home residents. Using objective measurement of cognitive functioning provided by neuropsychological testing could result in greater diagnostic accuracy and help provide for more accurate and appropriate treatment planning (J Am Med. Dir. Assoc. 2008; 9: 271-274).

Why Do We Do Screening

This tool was developed to aid primary care clinicians in caring for their patients who suffer primarily from Dementia and Alzheimer’s. However , many of the tools will also be useful for managing chronic depression and minor depression, secondary to Dementia and Alzheimer’s. The care management process recommended here builds on the earlier guidelines from the Agency for Health Care Policy and research (AHCPR)- now known as the Agency for Healthcare Research and Quality (AHRQ)- which have been updated and adopted from other evidence based sources including recently published multi-site trials and current studies.

Quick Facts About Psychological Counseling
• In psychological counseling, patients with depression work with a qualified health care professional who listens to them, talks and helps them correct overly negative thinking (which reinforces depressed mood) and improve their relationships with others
• Psychological counseling for depression is not talking about your childhood, but rather focused on current concerns and ways to address them.

Treating Depression with Psychological Counseling
Psychological counseling has been shown to be effective as antidepressants in treating many people with depression. Psychological counseling can be done individually (only you and a mental health professional). in a group (a mental health professional, you and others with similar problems) or it can be family or marriage counseling where a mental health professional, you and your spouse or family members participate: -More than half of the people-with mild to moderate depression respond well to psychological counseling. While the length of time that persons are involved in counseling differs, people with depression can typically expect to attend a weekly hour-long counseling session for 6- 20 weeks. If your depression is not noticeably improved after 6-12 weeks of counseling, this usually means that you need to try different treatment for your depression. Psychological counseling by itself is not recommended as the only treatment for persons whose depression is recurrent, more chronic or severe. Medication is needed for those types of depression and it can be taken in combination with psychological counseling.

What Can You Do To Help SPC and Senior Psychological Most Effectively Treat Your Depression With Psychological Counseling?

• Be honest and open and ask questions
• Work cooperatively by completing tasks assigned to you as part of the psychological counseling
• Be available and tell your mental health care professional how well the psychological counseling is working (e.g., whether your depression is getting better or worse).

Information for Clinicians, Administrators, and Primary Care Physicians about Screening

We believe that our integrated Model of Care (psychotropic management and therapy) and protocols developed over the years can provide your families with a distinct advantage in day-to-day operations resulting in a higher quality of care for your residents.

The integrated Model of care stresses regulatory compliance for long-term care facility by addressing medical management (F-329, F-4290), assessment, and administrative tag (F-501). Reduction in medications result in reduced falls and engage residents in more activities of daily living. This results in better participation in psychotherapy modules and behavior modification provided by higher training psychologists and therapists adhering to our protocols to further the quality of life of your clients. When residents respond to mediation and therapy, hospitalization is therefore reduced resulting in higher occupancy for the facility.

As you are aware, the more engaged the residents, the less prone to agitation they become. This reduces stress on your caregivers and turn over. You are bale to attract an retain happier staff and other clinical members of your facility. With stable occupancy and staff it is easier to plan for staffing, and scheduling, Educating physicians , family and the general public are also part of our responsibility.

If we can be of any assistance to you, please do not hesitate to contact any of us. We look forward to working with you.

Sincerely,
Leo J. Borrell

Reducing Psychotropic Drug use is Easy

67.7% of assisted living residents have dementia and 26.3% have an active non-cognitive psychiatric disorder. Screening has been found to be helpful in assisted living facilities and nursing homes.

Research shows that in nursing homes with treatment:
• 51% of participants with dementia and depression did improve their quality of life.
• 58% of those with depression alone, receiving counseling and medication recovered six months later and had a better quality of life.
• Only 25% of those receiving medication alone improved, but did not have a significantly better quality of life.
• Patients need to be seen 1-4 times per month in order to monitor-the constant fluctuation of behavioral and psychiatric symptoms and medical problems.
• Post stoke depression usually resolves in 6 months but can last two years.

In conclusion, patients who received psychotherapy (counseling) did 100% better than those that received medication alone. They also had a significant decrease in behavioral problems sooner and a better quality of life for longer.

Without psychotherapy, individuals with depression or dementia or both:
• 20% continued to-exhibit behavioral symptoms.
• 40% exhibited physically and/or verbally aggressive behavior

Because of these residents at nursing homes and assisted living facilities:
• Need to be routinely screened for depression
• All patients with behavioral problems need to be evaluated by a team of psychiatrist and mental health professionals.
• Most patients with many medical illnesses are not depressed.
• Staff needs to realize that many demented people will not spontaneously engage in activities because of depression or Alzheimer’s.
• Residents with dementia are taking several medications for problems such as insomnia or anxiety, the resident’s physician needs to review and possibly reduce the number of medications.

In conclusion, early evaluation and accurate comprehensive diagnosis is necessary. Medications alone are not enough. A comprehensive plan of 6-24 months with counseling is necessary to maximize results, prevent relapse and improve lie quality of life.

Screening is Important on Admissions to Nursing Homes

Psychiatric and Behavioral Symptoms in Dementia

• 80% of Nursing Home residents have psychiatric symptoms that progress unless properly treated.
• The elderly account for 20% of all suicides and have the greatest amount of depression, delirium, and dementia.
• Improving social skills, social involvement, the ability to participate in psychotherapy, coping skills, and avoid adjustment problems.
• Proper Diagnosis Important – Pseudo Dementia, Psychosis, and Cooperation.
• Psychotherapy minimizes the use of psychiatric medications and improves communicational development of the families.

Initiation of Services for Psychotherapy & Psychiatry
For All Primary Care Physicians and Charge Nurses

Please give completed form to the Director of Social Work.

Please refer to the list below as a guideline for determining which patients could benefit from psychiatric and/or psychotherapy treatment. If you have a question about whether or not a patient would benefit, please go ahead and refer that patient and an evaluation will be done to determine the course of treatment, if any.
Appropriate Mental Health Referrals include:
1. Residents who are newly admitted and dealing with adjusting to the loss of their previous residence and the nursing home setting.
2. Residents who are not new, but still struggling with adjusting to the nursing home setting and loss of their prior life.
3. Residents who are not complying with their medical or rehabilitation treatment needs.
4. Residents who are depressed about family or personal issues.
5. Residents who are nervous, anxious, or agitated.
6. Residents who have a history of depression, anxiety, or “nervous breakdown”.
7. Residents who have behavioral difficulties such as aggression, attempts at elopement, and resistance to A.DLS.
8. Residents who express a wish, intent or plan to die.
9. Residents who are dealing with chronic illness or disability (such as an amputation or gait disturbance with forced use of walker or wheelchair, etc).
10. Residents who are experiencing chronic pain and/or somatic symptoms that fail to remit with treatment.
11. Residents who are having difficulty resolving conflicts especially with their roommates.
12. Residents who are facing family conflicts.
13. Residents who are not responding to psychotropic medications.
14. Residents with previous psychiatric problems such as insomnia, depression, anxiety or previous psychiatric medications or hospitalizations.
15. Residents who are referred for Psychotherapy should also be seen by the Psychiatrist for medication review.

Please Evaluate: ? Psychiatric Medication Management ? Psychotherapy ? Other
Facility Name: ______________________________________________________________
Date: __________________ Referred by: ________________________________________
Send to DON or the Social Worker who is the coordinator of Mental Health referrals and if it is an emergency then call (210) 438-1900 or fax form to (800) 605-2138.

Lists of Patients:
Patient Name Room Number
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
SCREENING FOR PSYCHIATRIC MEDICATIONS AND PSYCHOTHERAPY REFERRALS

This form is to assist staff of non professionals in identifying behavior and psychiatric problems that require evaluation and treatment. Please have the Director of Social Work complete the request for Psychiatry & Psychotherapy Family Evaluation and forward it to SPC by fax at the number listed above.

Staff Member who completed this form:

Name: ____________________________________________

Primary Care Physician: ______________________________

REASON FOR REFERRAL
MEDICAL PROBLEMS/MEDICATION PROBLEMS

1. Having hallucinations/delusions/disordered thinking
2. Crying and/or persistent feelings of sadness/depression
3. Suicidal ideation (talks about suicide)
4. Persistent verbal/physical aggression toward others
5. Not coping well with terminal illness
6. Sexually inappropriate behaviors
7. Appears anxious/fearful
8. Significant change in eating/sleeping habits
9. Significant decline in physical/cognitive functioning or loss of limb
10. Death of family member or friend
11. Persistently low self esteem
12. Family issues that adversely effect resident’s emotional state
13. Has a new/old mental illness diagnosis Dx: ________________
14. Agitation and/or depression related to unrealistic expectations for rehabilitation
15. Somatization (obsessive health complaints not consistent with current physical status)
16. Withdrawal from activities/isolation
17. Resistant, uncooperative to counsel
18. Behavioral or cognitive side effects of psychoactive medications
19. Diagnosis of alcohol, drugs or pain medication dependence/addiction
20. Having significant difficulty adjusting to nursing home environment
21. Recent or impending loss of limb, speech or hearing
22. New medical problem that may affect behavior
23. Family concerns or problems
24. Evaluate medication

Other/Comments: _______________________________________________________
______________________________________________________________________

SENIOR PSYCHCARE, INC. IN AFFILIATION WITH SENIOR PSYCHOLOGICAL CARE, INC.
4314 Yoakum Blvd. Houston, Texas 77006 Phone: 713-850-0049 Fax: 713-850-0036 Toll-Free Fax: 800-605-2138
Web:http://www.SeniorPsychiatry.com
Patient Name:
Nursing Home:
Room #
Date Consultant :
Age:

FACILITY REFERRAL REQUEST FOR PSYCHIATRIC MEDICATIONS/PSYCHOTHERAPY CONSULTATIONS
(Short Form – for more detail use the Long Form)

Consent Form/ Face Sheet appreciated at time of consult. PCP order and info required before patient can be seen.
*******************TO BE COMPLETED BY REFERRAL MANAGER/ NURSING HOME STAFF***************
(CIRCLE) 48HRS / Routine: 3 to 7 Days Requested by______________________ Primary Care Physician______________
Urgent: Call Dr. Borrell at 713-850-0049; if no response, call cell phone 832-265-2882_______________________________
Nature of Urgency: ___________________________  Resistant to Care ? Family Session  Other: _________________
Please Check One:
Psychiatric
Psychotherapy
Both
Medicare Part A
SNF
Guardian
Chief complaint or immediate reason for Referral (Please Check all that Apply):
Depression
Anxiety
Psychosis
Agitation
Aggression
Suicide
Confusion
Other: ___________________
Chief complaint or immediate reason for Referral (Please Check all that Apply):
Depression
Anxiety
Psychosis
Agitation
Aggression
Suicide
Confusion
Other: ___________________
Dementia
Yes
No
Other Diagnoses: _________________________________________________________
A. EMOTIONAL SIGNS & SYMPTOMS (*E1,a,b,c,d,e,f,g,l,m,h,I) A resident’s emotional status interferes or enhances his/her ability to adjust to the institutional environment or to achieve self-actualization. Description:
A1. Anger
A2. Anxiety
A3. High Risk Behavior
A4. Reduced Social Interaction
A5. Depression/Sadness
A6. Sleep Problems
Comments: ______________________________________________________________________________________________________
PSYCHOSIS:
Delusions
Hallucinations Description: _________________________________________________

B. INTERACTIVE SIGNS & SYMPTOMS (*C-1, 2, 3, 4, 5) Communication problems may interfere with an individual’s ability to interact in positive ways, putting them at risk for isolation and sensory deprivation. The following are indicators.
B1. Aphasia
B2. Hearing
B3. Rarely understands others
B4. Rarely understood by others
B5. Sight Impairment
B6. Speech
Comments: ______________________________________________________________________________________________________

C. BEHAVIORAL SIGNS AND SYMPTOMS (*E4) Behavior associated with cognitive, emotional or diagnostic symptom logy may interfere with the efficient and safe operation of a facility. Such behaviors include:
C1. Disruptive Behaviors (also consider C3)
C2. Resistance to Care or ADL/Medications
C3. Inappropriate Behaviors (also consider C1)
C4. Aggressive Behaviors (Verbal/Physical)
C5. Wandering (also consider C2b, C2c, F3-Elopement)
C6. Weight Loss
Comments: ______________________________________________________________________________________________________

D. COGNITIVE SIGNS & SYMPTOMS: Many factors contribute to changes or decline. If addressed, symptoms may be minimized to improve quality of life.

____________________________________________________
D1. Confusion (also consider B3 and B4)
D2. Delusions
D3. Disorganized Speech
D4. MR/Developmental Disorder with Organic Condition
D5. Restlessness
D6. Short/Long-term memory problems
Comments: ______________________________________________________________________________________________________

E. SOCIAL SIGNS & SYMPTOMS Difficulties in social relationships may lead to emotional and/or behavioral problems.
E1. Adjustment Difficulty
E2. Conflict/Anger with family and/or friends
E3. Constantly Critical
E4. Loss of Close Family Member or Friend
E5. Sadness/Anger/Emptiness over Loss of Status
E6. Unhappy with Others
Comments: ______________________________________________________________________________________________________

F. OTHER CONCERNS
F1. Substance Abuse
F2. Discharging
F3. Elopement (also consider C5-Wandering)
F4. End Stage
F5. Wants and Needs
????F6. Pain ????F7. Evaluations
Comments: ______________________________________________________________________________________________________

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Office-Centred Background, Testing Can Help Detect Dementia

Dec
07

Taking a reliable history and administering a brief cognitive screening test can go a long way with regard to identifying Alzheimer’s disease and other dementias, according to one personal health practitioner.

Currently, too many patients with slight to normal dementia–patients with considerable functional impairment–are being missed within the office, according Dr. Kathleen R. Soch, associate professor in the division of family and community medicine at the Texas A&M Health Science Center in Corpus Christi.

But physicians can strengthen their track records by following a few straightforward steps: take a complete history, administer the Folstein Mini Mental Status Exam (FMMSE), rule out depression, execute standard laboratory testing, and contemplate ordering an imaging report, she said at the yearly assembly of the American Academy of Family Physicians.

Most physicians know to ask patients and their family members concerning memory loss, Dr. Soch said, but they do not recognize that family members constantly neglect problems with memory. A family caregiver could think their parent’s memory loss is ordinary for their age and that they are doing well, while in fact the memory injury may well be significant, she said. In these instances, families commonly go to the office simply because of the behavioral problems sometimes observed in dementia patients. When taking a history, consider other signs such as aphasia, apraxia, agnosia, along with issues with executive functionality.

For sufferers with signs of dementia, Dr. Soch recommends utilising the FMMSE as a vetting tool. The examination is one of the most widely used screening tests. It requires less than ten minutes to carry out within the office, and physicians can administer it themselves or instruct someone else in the office to execute it, she noted.

The FMMSE is a 30-point test that asks patients to distinguish where they are, the date and time of year, repeat words they have heard, recall words, spell a word backward, display simple verbal communication competencies, and carry out simple tasks. The cut off score is 24, and most people without any cognitive impairment should be able to score 29 or 30 on the assessment, she observed.

The examination has a sensitivity of 87% and a specificity of 82%. Most individuals who obtain a ranking of 24 or less will possess some form of cognitive impairment, but the test also will omit a lot of persons with primitive dementia, she said. The FMMSE also is less precise in patients with higher and lower levels of schooling.

Dr. Soch stated if she sees a patient who is extremely well educated and scores 28 or 29 points, she is more probable to contemplate a prognosis of dementia. On the other hand, sufferers who are not able to read will have issues with the examination regardless of any dementia evaluation. The test is additionally less accurate as patients grow older. Dr. Soch said she often scores the assessment more moderately for a patient above age 80 years.

For those patients who grade around the 24-point cutoff, Dr. Soch recommends ordering a few fundamental laboratory screens including CBC, a comprehensive metabolic panel, a test of TSH amounts, as well as a check of the patient’s vitamin [B.sub.12] level to rule out reversible factors. Physicians additionally need to ask for an imaging test, either a CT scan or MRI, to dispose of other possible conditions such as vascular dementia.

In addition, physicians should screen every affected person being assessed for dementia for depression. Depressive disorder impacts between 30% and 50% of dementia sufferers. Seeing that clinical depression typically presents along with exhaustion, psychomotor slowing, and apathy, it may possibly be misinterpreted like a worsening of dementia.

Dr. Soch advised physicians to maintain a high index of suspicion for clinical depression and contemplate a test with a selective serotonin reuptake inhibitor. He mentioned having no conflicts of interest.

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Advances in Imaging Expand Alzheimer’s Research

Nov
11

Trials of two new sup.18F imaging compounds have demonstrated the agents’ practical ability to attach to amyloid plaque, revealing their capacity to determine the buildup of amyloid over time with patients who develop or have procession of cognitive inadequacy and to differentiate alzheimer’s disease from ancillary types of dementia.

Studies of another genre of molecules, called luminescent conjugated oligothiophenes (LCOs), are beginning to expose differences in the ways in which amyloid is deposited in the brains of Alzheimer’s patients who are homozygous for the apolipoprotein E e4 allele (APOE e4) compared in conjunction with those who are homozygous for the e3 allele.

Florbetaben and florbetapir are both .sup.18F imaging compounds that bind to amyloid plaque in the human cerebral cortex. Both have shown hopefulness as agents that might be able to establish a firm physical diagnosis of the affliction, even early in the disease development–allowing for early, more efficacious healing, said Dr. Marwan Sabbagh, chief medical and technological executive at Banner Sun Health Research Institute, Sun City, Ariz.

“The field has been going a lot further towards the development of in vivo diagnostic agents that would provide for us to affirm a clinical diagnosis with rationally adequate promise and to go beyond using the necroscopy as the gold standard of Alzheimer’s diagnosis,” he said in an interview. “In the research setting, having a firm diagnosis will allow us to amass subjects for trials on the consideration with regard to whether they have amyloid in the brain. Present-day estimates are that as many as 15% of Alzheimer’s trial participants in actuality don’t have amyloid present, which probably contributes a lot of dissonance to the trials.”

Both florbetaben and florbetapir are akin to the Pittsburgh reagent B (PiB)–the first compound capable of visualizing amyloid plaques in a living subject during a positron-effusion tomography examination. But PiB has a very short half-life, intensely confining its large-range medical applicability, said Dr. Sabbagh.

“PiB PET was a great early stage in the dominion of amyloid imaging, but its broadening has been mired by the fact that it’s a .sup.11C compound, with a 20-minute half-life. The .sup.18F compounds don’t have that concern, and because of that, can be used in a way that is similar to the current fluorodeoxyglucose PET scan that is employed to diagnose carcinoma and other diseases. The .sup.18F amyloid agents are merely replacing fluorodeoxyglucose with another radioisotope. We will be able to make use of the same technology, just with radiologists who are educated on the new visualizations. But the commission in respect to the imaging won’t change the current technology–and that’s what is very captivating.”

Florbetapir Amyloid Imaging

Dr. Sabbagh has been an investigator on two florbetapir trials, both of which were presented at the assembly in Honolulu, which this newspaper covered remotely.

In a phase III trial of florbetapir, amyloid burden seen in PET scans extremely correlated with plaques seen in the very same patients at postmortem. A secondary analysis showed that duplicated florbetapir amyloid imaging could discern differences in the levels of amyloid binding over time in a number of healthy controls and patients with subdued cognitive inadequacy.

In the end-of-life study, headed by Dr. Christopher Clark of Avid, the radioisotope was employed to study plaque cumbrance in 35 Alzheimer’s patients with less than 6 months to live. After passing, brain sections from regions seen as plaque-impaired were examined histopathologically to define correlation with PET results.

The autopsies showed a considerable contingency between amyloid burden and both the visual ratings of the florbetapir PET scans and the patients’ average altered scores on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological block.

The longitudinal follow-up analysis, conducted by Dr. Reisa Sperling of Brigham and Women’s Hospital in Boston, comprised 47 patients with confirmed moderate cognitive debilitation (MCI) who were partnered in association with 62 aging healthy controls.

After a neuropsychological testing battery, all of the patients underwent PET imaging with florbetapir. The images were visually scored as amyloid positive or negative by three readers obscured to the diagnoses. Testing 6 and 12 months later included indicator reassessment, the dementia severity rating scale, and informant-based practicable determination.

Images were positive for amyloid in 38% patients with MCI at baseline, compared with 13% of the healthy controls. Florbetapir uptake correlated affirmatively with the dementia extremity appraisal measurement in both groups, with higher baseline amyloid correlated to greater functional impairment at follow-up.

By 1 year, none of the healthy controls had progressed to mci. Nevertheless, 4 of the 18 amyloid-positive MCI patients (22%) had progressed to Alzheimer’s disease, compared among 1 of the 29 amyloid-negative MCI patients (30%).

Although the results are promising, Dr. Sabbagh said, “it’s too soon to tell if florbetapir can be used as a prognostic agent,” as well as a diagnosis tic agent.

Dr. Sperling and Dr. Sabbagh have received research grants and subsidization from Avid.

Florbetaben Studies

The studies for Bayer’s compound, florbetaben, focused upon its affectivity and specificity, and its adequacy to set apart Alzheimer’s from unaffiliated forms of mental illness.

Dr. Osama Sabri of the University of Leipzig, Germany, lead a phase II trial that comprised 150 subjects imaged with the compound; 81 of these had probable Alzheimer’s disease. The PET images were visually rated by three blinded readers.

More than 95% of the images were calculated to be of high caliber. The investigators found that florbetaben had a sensitivity of 80% and a specificity of 90% for the perspicuity of Alzheimer’s patients from healthy controls. They also found that the APOE e4 was significantly more frequent in the amyloid-positive than the amyloid-negative patients (65% vs. 22%, respectively).

“The sensitivity and specificity were reasonably good for this compound,” Dr. Sabbagh said.

The characteristic clinical diagnosis endeavor, lead by Dr. Victor Villemagne of the Austin Hospital, Melbourne, used florbetaben PET imaging in 26 Alzheimer’s patients, 11 with frontotemporal lobar degeneration (FTLD), 6 with Lewy body dementia (LBD), and 26 healthy controls.

The Alzheimer’s patients showed significantly higher uptake of the compound in neocortical areas compared in conjunction with all the separate groups.

Practically all of the Alzheimer’s patients (96%) showed perfuse cortical uptake, although only white matter connecting was seen in the greatest number of the healthy controls (85%), FTLD patients (91%), and LBD patients (67%).

“This should not be unexpected, because frontotemporal dementia is a tauopathy, not related to amyloid, and Lewy body patients and normal controls should not have amyloid in their brain,” Dr. Sabbagh said. “It’s appropriate to deduce that this compound has the capacity to contrast one design of conceptual affliction from another.”

Both florbetaben studies were sponsored by Bayer Schering Pharma. Dr. Villemagne and Dr. Sabri have both received exploration grants and support from the company.

Plaque Differences Detected

New agents called luminescent conjugated oligothiophenes (LCOs) are beginning to demonstrate to scientists how APOE condition affects the way in which beta-amyloid protein aggregates in the brain of Alzheimer’s patients.

These compounds have shown that Alzheimer’s patients with a double clone of apoe e4 evolve beta-amyloid aggregates in brain blood vessels that are conspicuously different in structure and/or conformation from the aggregates in the brain substance, whilst within those who are homozygous for the APOE e3 allele, the protein clumps in both the vascular and essential structures take on evidently coequal organization, said Dr. Samuel E. Gandy, who serves as affiliate supervisor of the Alzheimer’s Disease Research Center at Mount Sinai School of Medicine, New York.

LCOs intercalate into lipid structures and fluoresce manifold colors depending upon the distinct conformational shape they take whenever encountering different proteins.

When the compounds happen upon amyloid plaques, they tend to phosphoresce orange; when they encounter neurofibrillary tau tangles, they tend to glow yellowish green.

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Loving Touch Makes A Difference

Oct
27

Traditional care offered in skilled nursing and assisted living lodgings often fails to pay attention to the psychosocial and psychosensory needs in relation with residents in later stages of retentiveness depletion. Many residents with advanced-stage Alzheimer’s disease and mutual dementias cannot interact in a community’s daily activities like bingo, trivia, or sing-alongs. While not engaged in activities they may become agitated, depressed, apathetic, or disinterested and are at an increased risk for falls.

A platform called namaste care, implemented in eight EPOCH Senior Living communities in Massachusetts and Rhode Island, offers an innovative line of action towards care that places residents with enhanced mental deficiency in a peaceful setting along with relevant activities charted specifically for them.

The term “namaste” comes from a Hindu statement that means “to deify the divine spark within.” The program, which was first implemented six years ago, has been precipitously prominent and is astoundingly affordable. EPOCH’s management found it could address the needs of some of its most delicate residents and foster their quality of essence without adding additional staff, purchasing costly supplies, and/or setting apart a spare room exclusively in contemplation of the program.

“From the beginning, it was a very moving experience,” says Joanna Cormac-Burt, EPOCH’s chief operating officer. “We had agitated residents who, whenever they were communicating with a caregiver in a quiet space along with pleasant chairs and delicate music, calmed down. Participants come to be further absorbed in cursory ways, instead of being lined up in wheelchairs in front of the nurse’s station, or sitting unaccompanied with a television.”

A different conception

EPOCH’s Namaste Care program provides a sense of tranquillity and composure to residents who are unable to interact with the larger environment of their skilled nursing community. From the individualized welcome each party receives at the start of a consultation to the peaceful environment where the program takes place, the individual resident is respected and cared for by means of a “loving touch” approach to activities in regard to daily living.

In EPOCH communities, Namaste Care-introduced by Joyce Simard, MSW, a private geriatric professional and EPOCH’s Alzheimer’s specialist-is offered seven days a week for six hours a day in a designated Namaste Care room.

The regular operation begins after most residents have finished breakfast and are toileted and groomed. Residents in the Namaste Care program are taken to the Namaste Care room, which features soft lighting, cushy, pleasant lounge chairs, calming music, and the calming scent of orchid.

Staff members greet residents according to their preferences. One resident goes by “Millie,” another prefers “Granny,” and a third might favor the more formalized “Dr. Powell.”

If a resident is in a wheelchair, she is placed in a comfortable lounge chair. Namaste Carers dispose of uncomfortable shoes, wrap a blanket around each resident, and checkup to be sure each and every resident is comfortable.

According to a new investigation reported in the American Journal of Alzheimer’s Disease and Other Dementias, each activity was proffered with a gentle, caring fashion with the caregiver dealing CarEgivingto the resident all through the activity.

The study, conducted by Simard and Ladislav Volicer, MD, describes how residents responded to facial softening and moisturizing. “The women seemed to be affected agreeably to the scent of Ponds Cold Cream, a standard article lots of them employed while they were younger. The men responded with the very same deportment to the scent of Old Spice.”

The staff also offered residents in the enterprise sips of liquid periodically. Since residents with broad dementia scarcely convey thirst and take a long time to drink even insubstantial amounts of liquid, hydration is an intrinsic component of the Namaste Care routine.

Namaste Carers have individual items at hand that can help residents interact with their environment, such as realistic stuffed dogs and cats. The residents frequently cheerfully interact with their “pet.” They talk to, cuddle with, and doze comfortably along with the stuffed animals.

Namaste Carers similarly supply clues in regard to the seasons to convey enjoyment towards residents who scarcely ever go outside. They employ what nature provides: daffodils and tulips in the spring, roses and geraniums in the summer, pumpkins and many-colored leaves in the fall, and snow or branches from fir trees in the winter.

Implementing The Program

Each EPOCH segment that introduced Namaste Care faced distinctive challenges. Various buildings had no extra capacity for a room to be designated just for Namaste Care.

The bellwether program, stationed in EPOCH’s community in Chestnut Hill, Mass., began in an empty room that had been a resident’s room. Simard and other staffers created a peaceful, comfortable place using a dab of paint, some homelike curtains, a quilt hung over the call lamp array, old furniture, and a few pictures. As the program grew, staff moved the Namaste Care room to the onetime dining room, where as many as 20 residents could come to the undertaking.

At EPOCH’s community in Norton, Mass., one of the pioneer nursing installations fashioned in the state, the wing that cared for the bulk of residents with advanced dementia had a single Day Room in use for meals, activities, and relatives visits. Each day after breakfast, staff transformed the room. The Namaste Carer lowered the lights, started the soothing music, turned on the fragrance diffuser, placed tablecloths on the round tables, and placed china tea sets and/or centerpieces on some of the tables. When residents were taken back to the room, it felt like a separate setting.

At EPOCH’s community in Weston, Mass., Administrator Adam Goldman introduced Namaste Care even during which time the building underwent renovations and the assembly of a new assisted living memory care wing. The program started in one room and moved three times until being settled in a fixed room, improving residents’ caliber of life, irrespective of the construction.

Namaste Care is exceptionally affordable. Communities to date carry lots of the supplies, such as nail clippers, basins, and emery boards. Face cloths and towels are furnished in laundry, and beverages and snacks are procurable from food service. Namaste Care requires a few comparatively inexpensive purchases, such as soft quilts, a compact disc (CD) player, CDs, lifelike stuffed animals, and an aroma diffuser. The largest amount is often a lunchroom or tea handcart with wheels that holds Namaste Care supplies.

Some communities additionally budgeted for comfy recliners that many homes have in the television room. Most communities did not have money for lounge chairs and used padded geri-chairs. More recently, EPOCH has begun investing $5,000 to $10,000 on lounge chairs when it creates a Namaste Care room. “It could probably be done for less, but we desired to use excellent-quality, longer-lasting chairs,” Cormac-Burt says.

EPOCH employed no superfluous board members to launch Namaste Care, instead training one nurse associate from each and every existing detail and assigning them to the program.

EPOCH’s administrators eventually added a Namaste Care position to each community’s budget at an added cost of $23,000. Over time, many employees at epoch have come to view being assigned to the Namaste Care room as a commendation or sought-after assignment.

A triumph development

Namaste Care immediately became a key practice offered by EPOCH. According to nurse reports, participants get fewer urinary tract infections and improved skin integrity, amid additional advancements.

“Sometimes we see a resident who is very discomforted until we emplace them in Namaste Care, and their whole affectation changes,” Cormac-Burt says. “This has happened again and again, which is why it’s so effective.”

Research now backs up this claim: The study found that residents attending Namaste Care for 60 days showed a curtailment in the use of anti-angst medications, improved employment in their environment, and a decrease in indicators in respect to mental confusion.

In addition, the smallest data set Challenging Behavior Profile was significantly decreased subsequent to admission in the Namaste program, indicating decreased liability in social exchange.

“For residents who are withdrawn or have reduced social interaction, the study showed that participating in the program had decreased most indicators in reference to mental confusion and decreased the demand for administration of anti-anxiety medications,” according to the study.

Staff and family members discern that residents are more and more conversational and aware of their environment. This is distinctly consequential to visiting family members.

“The Namaste program opened up a complete creative methodology for my mom and me to communicate in a loving and safe environment,” Damon Grew Syphers, the son of a certain resident who attended Namaste Care until her death, wrote recently. “We had periods of mixed times when we could touch, hug, and kiss. I sensed a restfulness and tranquility that I had not witnessed earlier in my mother. Mother felt treasured and wanted.”

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Perspectives From The Inside: Mental Soundness Problems With Regard To The Elderly In Nursing Homes

Oct
01

Occupant views as to comportment and emotive problems within nursing homes have been practically abandoned among the gerontology literature. In an attempt to better discern this forgotten perspective and its association to the views of professionals, residents (n = 92) and staff members (n = 74) of 20 nursing homes were surveyed concerning their views pertaining to problems of the inhabitant community. Confusion, wanting to return home, and depression were seen as the primary problems by both residents and staff. Results of the evaluation give evidence that staff members and residents assess the identical areas proportionately difficult, yet, in contrast to staff, the majority of residents affirm that external assistance is not desired and that they desire to discuss problems together with kin and/or friends.

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Diagnoses From Clinical Evaluations and Standardized Diagnostic Interviews Don’t Agree

Sep
29

A recent meta-analysis demonstrated that diagnoses yielded from clinical evaluations often do not concur with the results of structured and semistructured interviews-together called standardized diagnostic interviews (SDIs). Such a study could easily be overlooked as another dry and “methodological” investigation. However the implications of this meta-analysis are extensive.

Whenever clinicians pick up a journal to learn the latest clinical research, it is very probable that the patients described in those studies received their diagnosis in no small part from an SDI. Indeed, it is very difficult to issue a clinical study without using one. SDIs, which can be performed by both clinicians and nonclinicians, are designed so that interviewers ask the identical diagnostic queries in the same fashion, thereby minimizing unevenness within and across studies. The determinations of clinical research are plainly intended to be applicable to the clinician in commonplace clinical practice, where SDIs are rarely used. This discrepancy in diagnostic approach would not be a problem if, regardless of method, the results of both strategies generally led to the same diagnostic conclusion.

The trouble is that they do not. Instead, the diagnoses generated from SDIs incline to be different from the diagnoses derived from standard clinical evaluations. The 38 studies evaluated in our meta-analysis included about 16,000 patients and encompassed 10 different standardized interviews as well as a broad range of diagnoses, ages, and clinical settings. One requirement for the included studies was that the interviewers using SDIs and the clinical evaluators did not know the diagnostic outcomes of the other method.

Most of these studies calculated a ? statistic as their measure of accord between SDIs and clinical evaluations. While there is debate on the issue, ? values of 0.6 to 0.8 are generally considered acceptable to good, depending on the circumstance.

In our meta-analysis, the overall ? value across all diagnoses was 0.27. Some individual diagnoses clearly fared better than others. The ? for anorexia nervosa was 0.86 while the ? for generalized anxiety disorder was a paltry 0.19. Numerous diagnoses had a ? between 0.30 and 0.40.

SDIs come in 2 main types-structured and semistructured. Semistructured interviews allow for more flexibility in their delivery, whereas the questions on structured interviews are intended to be understood as written. While one might expect semistructured interviews to correspond more closely to clinical evaluations than to structured interviews, no statistical deviations were determined. There was some indication that accord was stronger in outpatient contexts and children. However, these improvements were modest and statistically nonsignificant when all prospective modifiers were recorded in a meta-regression.

These findings mean that if an SDI or a clinical evaluation produced a beneficial diagnosis for a particular disorder, the majority of time the other diagnostic system did not make the same diagnosis. Why was agreement overall so deficient? The study was not equipped to look immediately at this question, and the writers were careful not to attribute blame to either clinicians or SDIs. Interviewers using SDIs tended to return a higher number of diagnoses than clinicians. However, this difference cannot make a judgment about who is correct.

Possible sources for the poor agreement included features of both clinical evaluations and SDIs. Clinicians, on the one hand, might tend to pick a single diagnosis on the basis of clinical impressions-even if a patient satisfies criteria for several. They may likewise tailor their interviews more closely around the chief complaint and weigh contextual data, such as family history, in the diagnosis.

Clinicians may also hold back on making diagnoses out of concern about stigma. SDIs, by direct contrast, could provoke a lot of negative reactions because of the sheer number of questions that are typically asked. These interviews also lean to rely more heavily on the opinion of the patient or a parent about what represents a clinically substantial symptom.

To exemplify how these procedures may work in a clinical situation, consider the theoretical model of 15-year-old Billy who presents initially to a psychologist in the community.

Billy was neglected and abused by his biological parents who contended with their own mental health problems. He was taken from home at age three and lived in several foster homes before he was adopted into a sound household. He has been observed in manifold settings to be arbitrary, aggressive, disturbed, and inclined to profound behavioral blowups with minimal incitation. The adopted parents take Billy to a community clinician who directs an evaluation without an SDI and makes a diagnosis of posttraumatic stress disorder, noting the history of trauma and profound behavioral disturbance even in the absence of symptoms such as prominent flashbacks or nightmares. The clinician begins trauma-based psychotherapy and regards such interventions as eye movement desensitization and reprocessing.

After a raging episode at school, Billy is hospitalized at an academic medical center where an SDI is conducted as part of the admission procedure. According to this consultation, Billy meets standards for attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder. Treatment with a psychostimulant is initiated, and recommendations are made for parent behavioral education using a cognitive-behavioral context.

After discharge, Billy is assessed by a local psychiatrist who notices the degree of impairment and intense mood swings and diagnoses pediatric bipolar disorder-even without a history of prolonged manic symptoms lasting several days. The psychiatrist begins treatment with an antipsychotic agent and considers discontinuing the stimulant.

The example shows the decision making that can underlie the widely divergent diagnoses and treatment plans. Indeed, when these data were first presented as a poster at a meeting of the American Academy of Child and Adolescent Psychiatry, the informal comments made by viewers reflected the different perspectives. Those who inclined not to use SDIs interpreted these determinations as verification that SDIs were not useful, while academics who conducted research trials found the results to be validation that continuing utilization of SDIs was needed to create accurate diagnoses. Indeed, the source studies included in the meta-analysis also had disparate interpretations of their results. In some individual studies, the conception was couched in a way that diagnoses based on clinical evaluations were the “gold standard” so as to put SDIs to the test. Other studies were fashioned to challenge the cogency of diagnoses from clinical evaluations.

In a good deal of clinical research, disbelief about using either clinical evaluations or SDIs as the lone source of diagnostic information is reflected in the generally accepted practice of using a “best estimate” routine. Here, senior researchers reexamine the diagnostic outcomes of SDIs and assign final diagnoses after going over all the clinical data. This procedure is considered to add incremental validity to the ultimate diagnoses, although its usefulness has seldom been tested formally against prospective benchmarks that may be difficult to define.

My coauthors and I likewise discuss the possibility that the dichotomous nature of diagnoses may contribute to disagreement. For instance, if a clinical evaluation ascertains that a patient satisfies 5 of 9 criteria for the negligent items of ADHD while an SDI reports that 6 of 9 criteria are met, the final diagnosis is 100% disagreement (since at least 6 items are required)-even though the 2 methods may have agreed for 8 of 9 criteria. While divergence in such cases may be seen as something of an artifact, it does reflect current practice and the need to oftentimes make multiple decisions-such as whether to prescribe a medication.

In summary, our meta-analysis has revealed the somewhat alarming finding that diagnoses generated from SDIs (the prevailing method used in clinical research studies) and the diagnoses established from clinical evaluations (the prevailing method used in routine practice) oftentimes disagree. The origins of this disagreement are likely compound and a resultant of characteristics of both diagnostic methods. While researchers in practice oftentimes try to aggregate SDI results with clinical judgment, much remains to be learned about how scientists, clinicians, and perhaps DSM5 can synthesize often divergent information in the service of a sound and clinically meaningful assessment.

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Prolonged Donepezil Treatment in 565 Patients with Alzheimer’s Disease: Randomized Double-Blind Trial.

Sep
13

BACKGROUND:

Cholinesterase inhibitors create modest advances in cognitive and global assessments in Alzheimer’s disease. We proposed to ascertain whether donepezil produces noteworthy improvements in impairment, dependence, behavioral and psychogenic symptoms, carers’ psychological welfare, or delay in institutionalisation. If so, which patients benefit, from what dose, and for how long?

METHODS:

565 community-resident patients with mild to intermediate Alzheimer’s disease entered a 12-week run-in time period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who finished this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged befitting. Fundamental endpoints were entry to institutional care and advancement of disability, defined by departure of either two of four fundamental, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS). Outcome appraisals were sought for all patients and analysed by logrank and multilevel models.

FINDINGS:

Cognition averaged 0.8 MMSE (mini-mental state examination) points better (95% CI 0.5-1.2; p<0.0001) and functionality 1.0 BADLS points better (0.5-1.6; p<0.0001) with donepezil through the initial 2 years. No substantial benefits were ascertained with donepezil compared with placebo in institutionalisation (42% vs 44% at 3 years; p=0.4) or advancement of disability (58% vs 59% at 3 years; p=0.4). The proportionate risk of entering institutional care in the donepezil group compared with placebo was 0.97 (95% CI 0.72-1.30; p=0.8); the relative risk of progression of disability or entering institutional care was 0.96 (95% CI 0.74-1.24; p=0.7). Similarly, no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms, carer psychiatry, formal care costs, outstanding health care provider time, untoward events or deaths, or between 5 mg and 10 mg donepezil.

INTERPRETATION:

Donepezil is not cost efficient, with benefits below minimally applicable thresholds. More efficacious treatments than cholinesterase inhibitors are required for Alzheimer’s disease.

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Relative Frequency of Stages of Alzheimer-Related Lesions in Various Age Classes

Jun
27

Alzheimer’s disease is a relentlessly progressing dementing disorder. Major pathological earmarks include extracellular sediments of amyloid protein and intraneuronal neurofibrillary alterations. No remittances take place in the path of the disease. Prototypical amylaceous deposits originate in poorly myelinated regions of the basal neocortex. From there, they spread into bordering areas and the hippocampus. Deposits eventually infiltrate all cortical areas, including thickly myelinated primary fields of the neocortex (stages A-C).

Intraneuronal lesions arise initially in the transentorhinal region, then spread in a predictable fashion across other areas (stages I-VI). At stages I-II, neurofibrillary alterations develop preferentially in the absence of amyloid deposits. A balance of cases shows early development of amyloid deposits and/or intraneuronal changes. Advanced age is therefore not a requirement for the development of the lesions. Alzheimer’s disease is an age-related, not an age-dependent disease. The level of brain destruction at stages III-IV frequently results to the appearance of prototypical clinical symptoms. The stages V-VI representing fully developed Alzheimer’s disease are increasingly prevailing with increasing age. The arithmetical mean values of the stages of both the amyloid-depositing and the neurofibrillary pathology increase with age. Age is a risk element for Alzheimer’s disease.

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