Kuljeet Singh Anand

Potential Predictors of Hippocampal Atrophy in Alzheimer's Disease

The hippocampus is a vulnerable and plastic brain structure that is damaged by a variety of stimuli, e.g. hypoxia, hypoperfusion, hypoglycaemia, stress and seizures. Alzheimer’s disease is a common and important disorder in which hippocampal atrophy is reported. Indeed, the available evidence suggests that hippocampal atrophy is the starting point of the pathogenesis of Alzheimer’s disease and a significant number of patients with hippocampal atrophy will develop Alzheimer’s disease. Studies indicate that hippocampal atrophy has functional consequences, e.g. cognitive impairment. Deposition of tau protein, formation of neurofibrillary tangles and accumulation of β-amyloid (Aβ) contributes to hippocampal atrophy together with damage caused by several other factors. Some of the factors associated with the development of hippocampal atrophy in Alzheimer’s disease have been identified, e.g. hypertension, diabetes mellitus, hyperlipidaemia, seizures, affective disturbances and stress, and more is being learnt about other factors.Hypertension can potentially damage the hippocampus through ischaemia caused by atherosclerosis and cerebral amyloid angiopathy. Diabetes can produce hippocampal lesions via both vascular and non-vascular pathologies and can reduce the threshold for hippocampal damage. Carriers of the apolipoprotein E (ApoE)-ɛ4 genotype have been shown to have greater mesial temporal atrophy and poorer memory functions than non-carriers. In addition to giving rise to abnormal lipid metabolism, the ApoE-ε4 allele can affect the course of Alzheimer’s disease via both Aβ-dependent and -independent pathways. Repetitive seizures can increase Aβ-peptide production and cause neurotransmission dysfunction and cytoskeletal abnormalities or a combination of these. Affective disturbances and stress are proposed to increase corticosteroid-induced hippocampal damage in many different ways.In the absence of any specific markers for predicting Alzheimer’s disease progression, it seems appropriate to learn more about the various predictors of hippocampal atrophy that determine the progression of Alzheimer’s disease from mild cognitive impairment (MCI), and then attempt to address these. It would be interesting to know to what extent these predictors play a role in the development of MCI or hasten the conversion of MCI to fullblown Alzheimer’s disease. Finally, it would be useful to know the extent to which these predictors can worsen or aggravate existing Alzheimer’s disease.Of the clinically used drugs in Alzheimer’s disease, anticholinesterases have been shown to slow down the rate of progression of hippocampal atrophy. One study observed that the neuroprotective effect of these agents is possibly due to an anti-Aβ effect produced by cholinergic stimulation. Similarly, antihypertensive and antihyperglycaemic drugs (pioglitazone and insulin) have been shown to reduce the risk of Alzheimer’s disease or disease progression. Currently, there are no disease-modifying therapies available for Alzheimer’s disease. It has been suggested that for treatment to be most effective, the regimen must be started before significant downstream damage has occurred (i.e. before the clinical diagnosis of Alzheimer’s disease, at the stage of MCI or earlier). Since the hippocampus is a plastic structure and atrophy of this structure is closely related to the pathophysiology of Alzheimer’s disease, if we could control blood pressure, regulate blood sugar, treat behavioural and psychological symptoms, achieve satisfactory lipid lowering and maintain a seizure-free state in patients with Alzheimer’s disease, this may not only improve disease control but could also potentially affect the rate of disease progression.

Are vascular factors linked to the development of hippocampal atrophy in Alzheimer's disease?

The hipppocampus is a brain structure located deep in the temporal lobe and is notable for its susceptibility to neurotoxic stimuli. It plays a vital role in governing learning and memory. It has been shown to be damaged by variety of factors, e.g., hypoxia, hypoperfusion, hypoglycemia, stress, and seizures, and the list of such factors keeps growing with time. Recently, the role of vascular factors in Alzheimers disease in causing significant hippocampal damage has started emerging. Vascular factors are known to cause cerebral microlesions and contribute to many more brain pathologies. Though evidence supporting their effects on causing regional brain atrophy is mixed, several studies are indicating that medial temporal lobe may be particularly vulnerable to the damage caused by cardiovascular risk factors. Considering the association between neurodegeneration and vascular factors, a more rigorous scientific evaluation of the correlation between these two has been suggested.

Complementary and alternative medicine usage among Alzheimer's disease patients.

Use of complementary and alternative medicine (CAM) is common in chronic diseases. To investigate its relevance in Alzheimers disease (AD), we interviewed 38 patients and an attempt was made to determine the type of CAM used and reasons for using it.

Medication adherence survey of drugs useful in prevention of dementia of Alzheimer's type among Indian patients.

BACKGROUNDnGood medication adherence is the cornerstone of therapeutic success. Alzheimers disease (AD) is the most common type of dementia and most patients are old and on multiple drugs, and good compliance therefore is even more important in this population. Dementia of Alzheimers type (DAT) at present is yet to find a cure. Anticholinesterases and N-methyl-D-aspartate blockers are specific anti-AD therapies available. Hypertension, diabetes, and dyslipidemia can contribute to cognitive worsening. Keeping hypertension, diabetes, and dyslipidemia in control can therefore possibly prevent further cognitive decline.nnnMETHODSnPatients with subjective memory complaints (n = 75) were chosen randomly. Upon thorough neurological diagnostic work up for dementia, those with mild cognitive impairment/questionable dementia (Clinical Dementia Rating = 0.5) or those with AD were recruited in this study (n = 67). Those with hypertension, diabetes, and deranged lipid profile were further interviewed if they were able to take medicines regularly or not. An attempt was made to know causes of non-compliance.nnnRESULTSnForty-one percent of patients were not taking the drugs that have potential to prevent cardiovascular complications or ability to slow down cognitive decline in AD on regular basis. The lack of awareness, ignorance, medicines being too expensive, and the pressure of taking medicines regularly were cited as the reasons for non-compliance. Being illiterate and having low education contributed majorly to poor compliance in this study.nnnCONCLUSIONnCompliance to drugs that have potential or real ability to slow down cognitive decline is low in elderly people with DAT.

Yoga in Male Sexual Functioning: A Noncompararive Pilot Study

INTRODUCTIONnYoga is practiced both in developing and developed countries. Many patients and yoga protagonists claim that it is useful in improving sexual functions and treating sexual disorders.nnnAIMnWe wanted to study the effect of yoga on male sexual functioning.nnnMETHODSnWe studied 65 males (age range=u200324-60 years, average age=40±8.26 years) who were enrolled in a yoga camp and administered a known questionnaire, i.e., Male Sexual Quotient (MSQ) before and after 12 weeks session of yoga.nnnMAIN OUTCOME MEASURESnMSQ scores before and after yoga sessions.nnnRESULTSnIt was found that after the completion of yoga sessions, the sexual functions scores were significantly improved (P<0.0001). The improvement occurred in scores of all the domains of sexual functions as studied by MSQ (desire, intercourse satisfaction, performance, confidence, partner synchronization, erection, ejaculatory control, orgasm).nnnCONCLUSIONSnYoga appears to be an effective method of improving all domains of sexual functions in men as studied by MSQ.

Acute dystonic reaction with rivastigmine

Dystonic reactions are adverse extrapyramidal side effects and are common to antipsychotics, antiemetics, and a variety of other drugs. Rivastigmine, an anticholinesterase of carbamate variety, is well tolerated. A case of acute dystonic reaction with rivastigmine patch is being reported.

Migraine Relieved by Chilis

Spices are long known to be triggers of migrainous attacks. This Letter to the Editor reports a case of migraine with a paradoxical response of oral chili ingestion in aborting an acute attack of migraine. A 21-year-old right-handed female college student presented with a history of episodic headaches that were bilateral and alternating between left and right, frontotemporal in location, throbbing in character, and associated with photophobia and vomiting for the previous 3 years. There was no history of aura. The headache would start in the frontotemporal region and spread to affect whole of 1 side of the head, becoming generalized in the process. The attacks were partially relieved by sleep or aspirin/paracetamol. Pain became intense in the 6 months prior to presentation and could not be relieved by aspirin intake. During that time, the patient learned, accidentally, to abort the attacks using a one-and-a-half teaspoonful measurement of chili sauce. The response to chili ingestion was dramatic, and the attacks disappeared even while the patient was swallowing the chili sauce. The patient’s mother also possessed a history of migraine headache.There was no significant past medical or psychiatric history for our patient. A general physical and systemic examination was unremarkable. A detailed neurological examination was normal. A magnetic resonance (MR) imaging and MR angiography of the brain were unremarkable. An electroencephalogram was normal. Migraine is a common cause of chronic headache and is more common in young women. A number of relieving factors have been identified, which include cold stimuli, sitting or reclining in bed, isolation, inducing vomiting, scalp massage, changing diet, symptomatic medications, and becoming immobile during attack. Capsaicin is a naturally occurring alkaloid that is obtained from chilis. It is fat-soluble and is known to absorb from biologic surfaces like skin and mucosa. Analgesia produced results from a depletion of substance P in small fiber nociceptive neurons on which the transient receptor potential action channel (subfamily V), type 1 (TRPV1) is predominantly located. It binds to the vanilloid receptor TRPV1 that acts as a molecular integrator of chemical and physical painful stimuli. Capsaicin could possibly act as a calcitotin-related gene peptide release inhibitor. Topical capsaicin has been reported to relieve migraine attack in a substantial number of patients. In addition, capsaicin has been used intranasally in migraine and cluster headache effectively. A possible mechanism of headache relief, this case may be the modulation of peripheral and central sensitization of trigeminovascular pathways. To the best of our knowledge, this is the first instance of chilis being used as an aborting agent for acute migraine.

Headaches Induced by Pornography Use

A24-year-oldunmarriedmalesoftwareprofessional,notaknown caseofdiabetesorhypertension,presentedwithepisodesofsevere, explodingholocranialheadacheonwatchingpornographicvideos for the last 2 years. The headache would develop gradually over 5 min of viewing videos and would peak within 8–10 min. The intensitywassoseverethathehadtoabortwatching.Therewasno accompanying nausea, vomiting, or phonophobia. Progressively, he started to refrain from viewing videos as a means of avoiding headaches.Therewasnohistoryofheadacheassociatedeitherwith masturbation or with coitus. He had no history of head injury or meningoencephalitis in early childhood. There was no history suggestive of migraine in the family. He did not have a history suggestive of migraine, tension type or exertional headache. A physical and systemic examination was unremarkable. The neurological examination was normal. Magnetic Resonance (MR) Imaging, MR angiography of brain, and electroencephalogram were normal. He was advised non-steroidal anti-inflammatory agent combination (ibuprofen 400 mg and paracetamol 500 mg) halfanhourbeforewatching, towhichhereportedsignificantpain relief. Headaches associated with sexual activity are uncommon (Anand & Dhikav, 2009). Pre-orgasmic headache may be related tospace-occupyinglesions.Orgasmicheadacheisoftensevereand excruciating, whether due to aneurysm rupture or to the explosive component of benign coital headache. Post-orgasmic headache mayoccurasamanifestationofmigraine(Banerjee,1996).Astudy by Frese et al. (2003) stratified headaches associated with sexual activityandfound that there wasamale preponderance. It has two onset peaks (between 20–24 and 35–44 years). It can be dull type, increasing gradually with sexual excitement or explosive type. Paincanbebilateral and diffuseoroccipital.Headacheassociated with sexual activity has not been shown to be dependent upon specificsexualhabits andoccursoftenafterhavingsexualactivity with partner or during masturbation. There was a high co-morbidity with migraine and other types of headaches (e.g., benign exertionalandtension-type).Themechanismofheadacheinduced bysexualactivityismainlyatrigeminal-vasculareffect,butthereis a definite muscular component (Anand & Dhikav, 2009). Muscularcontractionplaysamajorrole,especiallyinmilderheadaches that become more intense as the sexual excitement increases. The probable mechanisms behind occurrence of headache in the present case could be alteration of nocioceptive mechanisms in the trigemino-vascular system with increased pain sensitivity associatedwitha heightenedemotional state associatedwithviewing pornorgraphy.

Mild cognitive impairment in Parkinson's disease and vascular risk factors among Indian patients.

Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders, 37, 315–326. Coen, R. F. et al. (1997). Distinguishing between patients with depression or very mild Alzheimer’s disease using the Delayed-Word-Recall test. Dementia and Geriatric Cognitive Disorders, 8, 244–247. Dhikav, V. and Anand, K. S. (2012). Caregiver burden of behavioral and psychological symptoms of dementia among Indian patients with Alzheimer’s disease. International Psychogeriatrics, 24, 1531– 1532. Hashidate, H. et al. (2012). Behavioral and psychological symptoms in elderly people with cognitive impairment. Differences between assessment at home and at an adult day-care facility. Nihon Koshu Eisei Zasshi, 59, 532– 543. Petersen, R. C. (2009). Early diagnosis of Alzheimer’s disease: is MCI too late? Current Alzheimer Research, 6, 324–330. Serra, L. et al. (2010). Are the behavioral symptoms of Alzheimer’s disease directly associated with neurodegeneration? Journal of Alzheimer’s Disease, 21, 627–639.

Hyperprolactinemia: An Unusual Cause of Erectile Dysfunction

Hyperprolactinemia due to pituitary adenoma is a rare causeof erectile dysfunction (ED). In this Letter, one such case inwhich erectile dysfunction preceded detection of pituitarymicroadenoma for many years is reported.A 35-year-old married man, not a known diabetic or hyper-tensive, presented with loss of libido and inability to achieve ormaintain erection for the past 8years. His morning erectionswere absent for the same duration. He was a non-smoker andnon-alcoholic and there was no history of prolonged substanceabuse.Therewasnohistoryoflocalorspinaltrauma.Hehadnoprior history of any psychiatric illness. General physical exam-ination revealed no gynecomastia, testicular atrophy or vari-cosities in scrotal area. Systemic and detailed neurologicalexaminations were also normal. Routine hematological andbiochemical investigations were within normal limits. PenileDoppler using high frequency probe showed normal corporacavernosa and spongiosium without evidence of any obviouscalcification. Cavernosal arteries were visualized and appearednormal, thus ruling out vascular cause of impotence. Contrastmagnetic resonance imaging (MRI) of the brain was normal,with homogenous enhancement of the pituitary.Four years after the onset of ED, he developed diminishedvision in the right half of both eyes. On direct questioning, thepatient revealed that he had intermittent accompanying head-ache, especially upon lifting heavy weights in the gymnasium.Repeat MRI scan showed a focal bulge on the left side of thepituitarygland,suggestiveofmicroadenoma.Hormonalprofilerevealed serum prolactin levels as high (31.6ng/ml; range =3.0–18.6ng/ml)andserumtestosteroneasnormal(9.6nMol/L;range for 20–50year-old men =4.56–28.2nMol/L). Serum FSHwas 4.01mIU/ml (range =1.55–9.74) and LH was 2.25mIU/ml(range=1.8–7.8). Thyroid hormone profile was normal. He wastreated with tablet cabergoline 0.25mg orally twice a week andthenincreasedto1mgorallytwiceaweek,afterwhichsignificantimprovement in both sexual function and visual deficits werereported.Clinicalpresentationofpituitaryadenomasmayvarydepend-ingonthelocationandsizeofthetumoranditssecretaryactivity.Adenomas are common during adulthood. Headaches, doublevision or other visual disturbances are usual presentations of apituitaryadenoma.Aprolactinomaisthemostcommonpituitaryadenoma leading to endocrine alterations with sexual conse-quences (e.g., amenorrhea, infertility, and gynecomastia).It is generallyrecognized that endocrinopathyis the rarest ofcauses of ED (Zeitlin & Rajfer, 2000). Obtaining serum testos-teroneandprolactinwithorwithoutthyroidhormoneprofilehasbeen advised as a cost effective screening tool to identify suchcases. Hyperprolactinemia per se is a rare cause of ED (Miller,Howards, & McLeod, 1980) as well but men with hyperprolac-tinemiareportsexualdysfunctionfrequently(Alfonso,Rieniets,&Vigersky,2006).ThiscaseillustratesthatEDcanbethesolepresenting feature of prolactin secreting pituitary tumors.References