Alzheimers disease - mild cognitive impairment countdown

Alzheimers dementia is usually diagnosed when memory loss and behavioural symptoms are readily apparent to their caregivers. At this stage the primary concern is to slow further deterioration. Caregivers at the clinic have often wished they could have looked into the future. Many have a history of Alzheimers disease in their elderly and wondered whether there was an earlier way of knowing. New knowledge gives us hope in this direction.

Alzheimers disease before memory loss

We now have the beginnings of a time line in the countdown to dementia. It is now possible to trace the beginnings of Alzheimers Dementia up to 20 years before its manifestation with memory loss and impaired function.

20

Beta-amyloid levels in the cerebrospinal fluid (CSF)  begin to drop 20 years before the onset of dementia. Alzheimer's Disease is characterized by toxic deposition of specific beta-amyloid (Aβ1-42) plaques around the brain cells. In normal aging beta-amyloid continues to increase in the brain fluid. However, in Alzheimers Dementia brain fluid beta-amyloid is markedly reduced.This is due to reduce clearance of beta-amyloid from the brain to the blood and CSF, as well as increased beta-amyloid plaque deposition in the brain.

15

15 years before dementia onset, beta-amyloid deposits can be detected by amyloid imaging PET scans. The best known amyloid PET tracer is Pittsburgh Compound-B (PIB). PIB retention is found in over 90% clinically diagnosed AD patients.
Tau protein accumulation inside the brain cells (neurons) is the second hallmark of Alzheimer's disease.  Microtuble associated protein tau (MAPT) in the brain fluid (CSF) increases with age. In Alzheimer's disease tau levels are markedly increased and reflects damage to the neurons and axons (brain cells). High CSF tau level differentiates mild cognitive impairment (MCI) from that which progresses to Alzheimer's disease.
Shrinkage or atrophy of the brain becomes detectable by MRI. This atrophy is visible in brain structures that are essential for the conscious memory of facts and events. These areas are located in the brain’s medial temporal lobe. This shrinkage is apparent on using a visual rating system which also measures its severity. The more extensive the brain atrophy, the more advanced the clinical stage of Alzheimer’s disease.

10

PET Scan (FDG-PET) changes in the way the brain uses glucose are apparent 10 years before dementia. These PET scan changes correlate with progression of Alzheimers disease.
Episodic memory loss begins at this stage. Episodic memory loss is the inability to learn new information or to recall previously learned information. It manifests as forgetting of recent events and conversations, repetitive questions, repetitive retelling of stories, forgetting the date, forgetting appointments, misplacing objects, losing valuables, and forgetting that food is cooking on the stove. The formation of new episodic memories requires intact medial temporal lobes of the brain; these are progressively destroyed in Alzheimers disease.

5

Mild cognitive impairment (MCI) deveelops 5 years before dementia. People with mild cognitive impairment have problems with thinking and memory loss. Mild cognitive impairment does not interfere with everyday activities. Persons with mild cognitive impairment are often aware of their forgetfulness.
Preventive therapies for Alzheimers disease (AD) require the development of biomarkers that are sensitive to subtle brain changes occurring in the preclinical stage of the disease. Early diagnostics is necessary to identify and treat at risk individuals before irreversible neuronal loss occurs.
Sources

1. Bateman R. The dominantly inherited Alzheimer's network trials: an opportunity to prevent Alzheimer's disease. Program and abstracts of the Alzheimer's Association International Conference 2012; July 14-19, 2012; Vancouver, British Columbia, Canada. Featured research session F3-04
2. Christian Humpel. Identifying and validating biomarkers for Alzheimer's disease. Trends Biotechnol. 2011 January; 29(1): 26–32. doi: 10.1016/j.tibtech.2010.09.007
3. Duara R, Loewenstein DA, Potter E, Appel J, Greig MT, Urs R, Shen Q, Raj A, Small B, Barker W, Schofield E, Wu Y, Potter H. Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease. Neurology. 2008 Dec 9;71(24):1986-92.
4. Mosconi L, Berti V, Glodzik L, Pupi A, De Santi S, de Leon MJ. Pre-clinical detection of Alzheimers disease using FDG-PET, with or without amyloid imaging. J Alzheimers Dis. 2010;20(3):843-54.

ADHD treatment improves academic performance

ADHD treatment improves academic performance

ADHD medication enhances academic performance when started early. ADHD drug treatment improves reading ability in children with Attention Deficit Hyperactivity Disorder (ADHD) and Dyslexia. New research shows that drug treatment of ADHD also improves maths ability especially when started early - at least by the 4th standard. Children starting treatment a year or two later show progressively greater declines in academic performance.

ADHD is characterised by inattention and hyperactive-impulsive behaviour. Parents who bring their children to the clinic are focused only on issues arising from the child's hyperactivity. Impairments due to inattention are not immediately apparent in the pre-school years. Depending on the severity of ADHD, inattention is unmasked when the child enters academic life in primary school or during the transitions to middle school, high school, and college. At each  of these stages an increasing demand is placed on the cognitive faculty of attention which the child's brain is not capable of meeting.

Children with ADHD fail to absorb formative academic concepts in primary school. However, rote learning or tutoring by the parents helps the child clear these initial stages. It is only later when the cognitive load exceeds the child's capacity to concentrate that academic problems become manifest. By this time the child's academic progress has already taken a downward trajectory. Reversing this trend and repairing the negative impact on the child's self-esteem entails considerably more effort, time and sustenance at these later stages. The earlier treatment for ADHD is initiated, the better.

Inattention in ADHD is due  to altered brain proteins. These are involved in modulation of the neurochemical - dopamine. This results in reduced dopamine in the synapse (fluid filled space that transmits information from one brain cell to another).  Altered dopamine modulation in the frontal lobe of the brain makes the child impulsive and distractible. ADHD medications act on dopamine and noradrenaline receptors to keep each dopamine molecule longer in the synaptic cleft. Dopamine is then available to stimulate the receptors for longer.

Parental concerns regarding side-effects of ADHD drug treatment on the developing child are largely unfounded. There is now evidence that shows long-term treatment with therapeutic doses of ADHD medication does not affect the developing brain or other standard measures of growth. ADHD drug treatment also does not increase the risk for addiction. As with any other medication side effects can arise at the start of treatment. Adherence to the review schedule will help monitor and mitigate these. All medication is prescribed after carefully weighing the risks and benefits. In the case of ADHD the risks are poor academic functioning and subsequent narrowing of career options at best, to dropping out or expulsion from school and subsequent delinquency at the worst. The benefits of treatment are highlighted in the  report card shown above.

Drug treatment of ADHD enhances academic performance and learning by reducing the inattention and hyperactivity of ADHD. The child with ADHD has attentional and impulse control issues. Inattention and hyperactivity interfere with classroom learning. The earlier ADHD treatment is started the better the outcome in terms of academic achievement. Many children have experienced these benefits.

References

1. Kathryn E Gill, Peter J Pierre, James Daunais, Allyson J Bennett, Susan Martelle, H Donald Gage, James M Swanson, Michael A Nader and Linda J Porrino. Chronic Treatment with Extended Release Methylphenidate Does Not Alter Dopamine Systems or Increase Vulnerability for Cocaine Self-Administration: A Study in Nonhuman Primates. Neuropsychopharmacology , (18 July 2012) | doi:10.1038/npp.2012.117
2. Penny Corkum, Melissa McGonnell and Russell Schachar. Factors affecting academic achievement in children with ADHD. Journal of Applied Research on Learning. Vol. 3, Article 9, 2010.
3. Zoëga, et al. A Population-Based Study of Stimulant Drug Treatment of ADHD and Academic Progress in Children. Pediatrics 2012;130:2011-3493

Sexual Dysfunction and Relationships

The Erectile Dysfunction-Relationship Cycle

Erectile and sexual dysfunction in an ongoing relationship usually reflects difficulties between the partners. Relationship problems interfere with sexual feelings and cause or worsen erectile dysfunction.  Any experience that hinders the ability to be intimate, that leads to a feeling of inadequacy or distrust, or that develops a sense of being unloving or unlovable may result in erectile dysfunction.  Successive episodes of impotence are reinforcing. The man becomes increasingly anxious about his next sexual encounter. Erectile dysfunction is worsened by anticipatory anxiety about achieving and maintaining an erection interferes.  Sexual dysfunction interferes with pleasure in sexual contact and reduces ability to respond to sexual stimulation.

Erectile Dysfunction in the relationship cycle

In the early years of the relationship

• Lack of knowledge - there is a refractory period after sex before you can get the next orgasm. This refractory period increases gradually from a few minutes in teenagers to many days  in the elderly. Misguided enthusiasm after a period of separation causes a one-off problem with erection. This  is transient erectile problem is further reinforced by succeeding anxiety.
• Lack of privacy - the young couple moves into the parental home and has minimal access to privacy. Sex is a hurried activity with the focus on orgasm. Intimacy is not fostered. Subsequently there is dissatisfaction and a further build-up of anxiety.
• Stressors - careers with long working hours, night shift work and work from home leaves little time for the emotional intimacy that is requisite for sexual intimacy.

Middle phase

• Lifestyle changes - a sedentary  life style coupled with an indiscriminate diet result in obesity, a leading risk factor for erectile dysfunction. Excessive alcohol intake, and smoking have a direct impact on sexual functioning.
• Infidelity - is a major cause of anxiety and erectile dysfunction in the middle phase of the relationship. This  is especially so when the infidelity arises from insecurity - the man or woman attempting to prove continued youthfulness and desirability outside the relationship.

Later years

• Medical issues - chronic illnesses such as diabetes, and heart disease are commonly associated with erectile dysfunction.

What to do

• Don't panic - anxiety worsens erectile dysfunction. An occasional problem with  erection is not a reflection on your masculinity, and does not necessarily indicate a long term erectile dysfunction. Don't immediately try  to 'prove' yourself. Give it a days break to be safely out of the refractory period. There  will be  no trouble in the  next sexual encounter.
• Communicate - reassure your  partner of your continuing sexual interest in her. Communicate openly about  your condition. Involving your  partner improves the outcome of treatments for erectile dysfunction.
• Quit smoking
• Lose weight, exercise regularly
• Get treatment for alcohol or drug problems
• Work through relationship issues. Consider counseling if unable to work through  problems on your own.
• Depression, anxiety and stress related mental health issues should be addressed. Don't ignore them.

Whom to see for sexual dysfunction

• Consult a qualified psychiatrist. He or she  is the only person with the knowledge, training, and experience to deal with the psychological and medical issues that result in sexual dysfunction. The psychiatrist will also address issues in the relationship that are perpetuating the erectile dysfunction.
• Avoid self-styled sex therapists and sexologists

References:

1. Kubin M, Wagner G, Fugl-Meyer AR. Epidemiology of erectile dysfunction. Int J Impot Res. 2003 Feb;15(1):63-71.
2. McCabe M, Althof SE, Assalian P, Chevret-Measson M, Leiblum SR, Simonelli C, Wylie K. Psychological and interpersonal dimensions of sexual function and dysfunction. J Sex Med. 2010 Jan;7(1 Pt 2):327-36.
3. Metz ME, Epstein N. Assessing the role of relationship conflict in sexual dysfunction. J Sex Marital Ther. 2002 Mar-Apr;28(2):139-64.
4. Nina Bingham. Research Findings on Sexual Dysfunction, Intimacy and Conflict in Heterosexual Couples. Accessed 30-Jun-2012

Cannabis, teenagers and schizophrenia

Cannabis or marijuana use by teenagers and adolescents is highly associated with the onset of psychosis and schizophrenia. Cannabis goes by many names including hash, pot, grass, weed, or ganja. This gateway drug is falsely thought to be innocuous and as having no lasting effects. Cannabis use by teenagers is often not recognised as a problem. Cannabis is cheap and easily accessible in most student populations. Pune is a major hub for the cannabis drug trade. This week a quarter tonnne of ganja was found dumped in a well. Cannabis use is rampant in Pune colleges and hostels, where students assiduosly guard and maintain their 'stash'. During the 57th National School Games the highest number of students testing positive for marijuana came from Maharashtra.

Regular cannabis use increases the risk for schizophrenia and psychosis by upto 4 times. There is increasing evidence that cannabis use can precipitate schizophrenia in vulnerable individuals. This is especially so with early onset use of cannabis. Cannabis also exacerbates symptoms of schizophrenia in those who have already developed the disorder. Psychotic disorders like schizophrenia involve disturbances in the dopamine neurotransmitter systems of the brain. Δ9-tetrahydrocannabinol (THC) - the key neurochemical in cannabis - interacts with dopamine to adversely affect its functioning by multiple mechanisms.

Teenagers are especially vulnnerable to the schizophrenia-inducing effects of cannabis. Cannabis like substances (anandamide) called endocannabinoids, produced by the body, play an important role in several processes of brain maturation. Regular marijuana use affects this process of brain maturation in teenagers. Schizophrenia is also a disorder of brain maturation. Disruption of the endocannabinoid system in the adolescent brain by exposure to cannabis interferes with brain maturation. This provides a mechanism to increase the risk for development of schizophrenia in adolescence.

How to cut down and stop cannabis use

1. Write down a list of reasons for wanting to stop - you will need to review this at times when you are feeling low or experiencing craving.
2. Tell someone you trust that you are quitting
3. Get rid of the paraphernelia for smoking cannabis - the stash, wrappers, lighters, matches. You may be surprised at the number of places where small amounts are hidden. Get rid of it all.
4. Take measures to prevent fresh procurements - avoid places and people associated with replenishments
5. Make a list of things to do to occupy the time freed-up from procuring and using cannabis.
6. Review your list of reasons and things to do when you feel low and when craving is intense.

References

1. Paola Casadioa, Cathy Fernandesb, Robin M. Murray, Marta Di Forti. Cannabis use in young people: The risk for schizophrenia.  Neuroscience & Biobehavioral Reviews. Volume 35, Issue 8, August 2011, Pages 1779–1787. doi:10.1016/j.neubiorev.2011.04.007
2. Degenhardt L, Hall W. Is cannabis use a contributory cause of psychosis? Can J Psychiatry. Aug 2006;51(9):556-65.
3. Deepak Cyril D’Souza,Richard Andrew Sewell,and Mohini Ranganathan. Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci. 2009 October; 259(7): 413–431. Published online 2009 July 16. doi: 10.1007/s00406-009-0024-2

Alcohol and Happiness - do they mix?

Alcohol and happiness don't mix - definitely not when taken in excess, and definitely not in the long term. The relationship between adverse alcohol use and unhappiness is reciprocal - unhappy people tend to drink hazardously, and vice versa. This effect increases over time as demonstrated by a 15-year study that followed-up adult twins in 1975, 1981, and 1990.

Passing out while drinking is significantly more likely in dissatisfied people

Blackouts or passing out while consuming alcohol is an indication of unhappiness.

Dissatisfied people are more likely to have a pattern of binge drinking.

Binge drinkers are more likely to be dissatisfied with life. A pattern of binge drinking on weekends negates any beneficial effects of moderate alcohol use.

Excessive alcohol use increases dissatisfaction and unhappiness. Alcohol, even in moderation does not reinforce feelings of well being, pleasure, happiness or joy. Moderate drinking does not reduce unpleasant feelings.

Don't drink alcohol to regulate your mood, it leads to more grief.

References

1. H. Koivumaa-Honkanen; J. Kaprio; T. Korhonen;, R.J. Honkanen; K. Heikkilä; M. Koskenvuo. Self-reported Life Satisfaction and Alcohol Use: A 15-year Follow-up of Healthy Adult Twins. Alcohol and Alcoholism. 2012;47(2):160-168.
2. R. Curtis Ellison, Marjana Martinic. The Harms and Benefits of Moderate Drinking: Findings of an International Symposium. May 2007 supplement to Annals of Epidemiology.
3. Gustafson R. Does a moderate dose of alcohol reinforce feelings of pleasure, well-being, happiness and joy? A brief communication. Psychol Rep. 1991 Aug;69(1):220-2.