Dementia: A Focused Review

By Raj K. Kalapatapu, MD | February 9, 2010

Dr Kalapatapu is a fellow in the department of addiction psychiatry at Columbia University, New York State Psychiatric Institute, New York. He completed a fellowship in geriatric psychiatry at the Mount Sinai School of Medicine in New York in July 2009. The author reports no conflicts of interest concerning the subject matter of this article and has declined the honorarium for this article.

Huntington disease dementia

A trinucleotide repeat in the gene encoding for the huntingtin protein causes Huntington disease. The prevalence of Huntington disease is approximately 7 to 10 cases per 100,000 in white populations and is lower in mixed white, black, and Asian populations.⁴⁰

In the early stages, cognitive impairments in attention, concentration, visuospatial ability, emotional processing, and memory become noticeable. In later stages, cognitive impairments in planning, problem solving, cognitive flexibility, and freedom from distractibility become evident. Cognitive impairments worsen to dementia, which is characterized by slow information processing, decreased motivation, depression, apathy, and personality changes.

Language is relatively spared. Psychosis and affective disturbances, including depression, suicide, and mania, develop in many patients. In the early stages, structural changes are relatively specific and primarily affect the caudate and putamen. Psychomotor, executive, visuospatial, and memory deteriorations appear to develop from basal ganglia pathology, which disturbs normal cognitive processes mediated by frontostriatal circuits. Resting-state and neurocognitive-activation functional imaging studies suggest that striatal and cortical dysfunction contributes to cognitive status.⁴¹

Treatments must be targeted to the stage of the disease. Nonpharmacological treatments for cognitive impairment include the use of schedules, “to do” lists, routines, and cues to help memory retrieval. Symptomatic treatment is the foundation of pharmacological management. However, a review of 22 trials that comprised 1254 patients who had Huntington disease found that no intervention produced a robust conclusive symptomatic effect.⁴² A review of another 8 trials involving 1366 patients found that no intervention modified disease progression.⁴³ Depressive symptoms may respond to SSRIs, mirtazapine(Drug information on mirtazapine), or venlafaxine, although further data are needed to determine efficacy and safety.⁴⁴

Conclusion

Newer treatment strategies and clearer descriptions of disease processes that cause dementia are two of the goals of current research (Table 6).

The concept of cognitive impairment entails many different terms, such as dementia, amnestic disorder, CIND, cognitive changes associated with normal aging, mild cognitive impairment, vascular cognitive impairment, and VCIND. The workup must be individualized to each patient’s unique presentation. A proactive and detailed investigation for any possible etiology is warranted. Management of any patient with dementia must be within the context of a comprehensive treatment plan.

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by Rajnikant Kothari | December 06, 2010 8:24 PM EST

Excellent

References

1. Lyketsos CG. Dementia and milder cognitive syndromes. In: Blazer DG, Steffens DC, eds. The American Psychiatric Publishing Textbook of Geriatric Psychiatry. 4th ed. Washington, DC: American Psychiatric Publishing; 2009:chap 13.
2. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183-194.
3. Panza F, Frisardi V, Capurso C, et al. Possible predictors of vascular cognitive impairment–no dementia. J Am Geriatr Soc. 2009;57:943-944.
4. Stephan BC, Matthews FE, Khaw KT, et al. Beyond mild cognitive impairment: vascular cognitive impairment, no dementia (VCIND). Alzheimers Res Ther. 2009;1:4.
5. Sadavoy J, Jarvik LF, Grossberg GT, Meyers BS, eds. Comprehensive Textbook of Geriatric Psychiatry. 3rd ed. New York: WW Norton; 2004.
6. Blazer DG, Steffens DC, Busse EW, eds. Essentials of Geriatric Psychiatry. Washington, DC: American Psychiatric Publishing; 2007.
7. American Psychiatric Association, Work Group on Alzheimer’s Disease and Other Dementias. Practice Guideline for the Treatment of Patients With Alzheimer’s Disease and Other Dementias. 2nd ed. Washington, DC: American Psychiatric Association; 2007. http://www.psychiatryonline.com/pracGuide/loadGuidelinePdf.aspx?file=AlzPG101007. Accessed December 25, 2009.
8. Coluccia D, Wolf OT, Kollias S, et al. Glucocorticoid therapy-induced memory deficits: acute versus chronic effects. J Neurosci. 2008;28:3474-3478.
9. Vella-Brincat J, Macleod AD. Adverse effects of opioids on the central nervous systems of palliative care patients. J Pain Palliat Care Pharmacother. 2007;21:15-25.
10. Simon RP, Greenberg DA, Aminoff MJ. Disorders of cognitive function. In: Clinical Neurology. 7th ed. New York: McGraw-Hill; 2009:chap 1.
11. Finney GR. Normal pressure hydrocephalus. Int Rev Neurobiol. 2009;84:263-281.
12. Factora R, Luciano M. When to consider normal pressure hydrocephalus in the patient with gait disturbance. Geriatrics. 2008;63:32-37.
13. Graff-Radford NR. Normal pressure hydrocephalus. Neurol Clin. 2007;25:809-832, vii-viii.
14. Aisen PS, Schneider LS, Sano M, et al; Alzheimer Disease Cooperative Study. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300:1774-1783.
15. Weir DR, Jackson JS, Sonnega A. National Football League Player Care Foundation: Study of Retired NFL Players. Institute for Social Research, University of Michigan; 2009. http://umich.edu/news/Releases/2009/Sep09/FinalReport.pdf. Accessed December 25, 2009.
16.Stone CK, Humphries RL. Head injuries. In: CURRENT Diagnosis & Treatment: Emergency Medicine. 6th ed. New York: McGraw-Hill; 2008:chap 20.
17. Simon RP. Current diagnosis and treatment of sexually transmitted diseases. In: Klausner JD, Hook EW, eds. Neurosyphilis. New York: McGraw-Hill; 2007:chap 20.
18. Bird TD. Genetic aspects of Alzheimer disease. Genet Med. 2008;10:231-239.
19. Sweet RA, Wilkosz PA. Genetics. In: Blazer DG, Steffens DC, eds. The American Psychiatric Publishing Textbook of Geriatric Psychiatry. 4th ed. Washington, DC: American Psychiatric Publishing; 2009:chap 6.
20. Kalapatapu RK, Neugroschl JA. Update on neuropsychiatric symptoms of dementia: evaluation and management. Geriatrics. 2009;64:20-26.
21. Kalapatapu RK, Schimming C. Update on neuropsychiatric symptoms of dementia: antipsychotic use. Geriatrics. 2009;64:10-18.
22. Aggarwal NT, Decarli C. Vascular dementia: emerging trends. Semin Neurol. 2007;27:66-77.
23. Wetterling T, Kanitz RD, Borgis KJ. Comparison of different diagnostic criteria for vascular dementia (ADDTC, DSM-IV, ICD-10, NINDS-AIREN). Stroke. 1996;27:30-36.
24. Wiederkehr S, Simard M, Fortin C, van Reekum R. Comparability of the clinical diagnostic criteria for vascular dementia: a critical review. Part I. J Neuropsychiatry Clin Neurosci. 2008;20:150-161.
25. Román GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993;43:250-260.
26. Mendez MF, Lauterbach EC, Sampson SM. An evidence-based review of the psychopathology of frontotemporal dementia: a report of the ANPA Committee on Research. J Neuropsychiatry Clin Neurosci. 2008;20:130-149.
27. Weder ND, Aziz R, Wilkins K, Tampi RR. Frontotemporal dementias: a review. Ann Gen Psychiatry. 2007;6:15.
28. McKhann GM, Albert MS, Grossman M, et al; Work Group on Frontotemporal Dementia and Pick’s Disease. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol. 2001;58:1803-1809.
29. Blass DM, Rabins PV. Depression in frontotemporal dementia. Psychosomatics. 2009;50:239-247.
30. Lippa CF, Duda JE, Grossman M, et al; DLB/PDD Working Group. DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology. 2007;68:812-819.
31. Dodel R, Csoti I, Ebersbach G, et al. Lewy body dementia and Parkinson’s disease with dementia. J Neurol. 2008;255(suppl 5):39-47.
32. McKeith IG, Dickson DW, Lowe J, et al; Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium [published correction appears in Neurology. 2005;65:1992]. Neurology. 2005;65:1863-1872.
33. Burn DJ. Cortical Lewy body disease and Parkinson’s disease dementia. Curr Opin Neurol. 2006;19:572-579.
34. Hanson JC, Lippa CF. Lewy body dementia. Int Rev Neurobiol. 2009;84:215-228.
35. Truong DD, Bhidayasiri R, Wolters E. Management of non-motor symptoms in advanced Parkinson disease. J Neurol Sci. 2008;266:216-228.
36. Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22:1689-1707; quiz 1837.
37. Park A, Stacy M. Non-motor symptoms in Parkinson’s disease. J Neurol. 2009;256(suppl 3):293-298.
38. Weintraub D, Comella CL, Horn S. Parkinson’s disease—part 3: neuropsychiatric symptoms. Am J Manag Care. 2008;14(2 suppl):S59-S69.
39. Miyasaki JM, Shannon K, Voon V, et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66:996-1002.
40. Walker FO. Huntington’s disease. Semin Neurol. 2007;27:143-150.
41. Montoya A, Price BH, Menear M, Lepage M. Brain imaging and cognitive dysfunctions in Huntington’s disease. J Psychiatry Neurosci. 2006;31:21-29.
42. Mestre T, Ferreira J, Coelho MM, et al. Therapeutic interventions for symptomatic treatment in Huntington’s disease. Cochrane Database Syst Rev. 2009;(3):CD006456.
43. Mestre T, Ferreira J, Coelho MM, et al. Therapeutic interventions for disease progression in Huntington’s disease. Cochrane Database Syst Rev. 2009;(3):CD006455.
44. Cardoso F. Huntington disease and other choreas. Neurol Clin. 2009;27:719-736, vi.
45. American Academy of Neurology Guideline Summary for Clinicians: Detection, Diagnosis, and Management of Dementia. http://www.aan.com/professionals/practice/pdfs/dementia_guideline.pdf. Accessed December 25, 2009.
46. Kalapatapu RK, Chambers R. Novel objective biomarkers of alcohol use: potential diagnostic and treatment management tools in dual diagnosis care. J Dual Diagn. 2009;5:57-82.
47. American Psychiatric Association, Work Group on Delirium. Practice Guideline for the Treatment of Patients With Delirium. Washington, DC: American Psychiatric Association; 1999. http://www.psychiatryonline.com/pracGuide/loadGuidelinePdf.aspx?file=Delirium_Inactivated_04-16-09. Accessed December 25, 2009.
48. Welsh-Bohmer K, Attix DK. Neuropsychological assessment of dementia. In: Blazer DG, Steffens DC, eds. The American Psychiatric Publishing Textbook of Geriatric Psychiatry. 4th ed. Washington, DC: American Psychiatric Publishing; 2009:chap 11.
49. Shah RS, Lee HG, Xiongwei Z, et al. Current approaches in the treatment of Alzheimer’s disease. Biomed Pharmacother. 2008;62:199-207.
50. Solomon PR, Murphy CA. Early diagnosis and treatment of Alzheimer’s disease. Expert Rev Neurother. 2008;8:769-780.
51. van Marum RJ. Current and future therapy in Alzheimer’s disease. Fundam Clin Pharmacol. 2008;22:265-274.
52. Okura Y, Matsumoto Y. DNA vaccine therapy for Alzheimer’s disease: present status and future direction. Rejuvenation Res. 2008;11:301-308.
53. Gong CX, Iqbal K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem. 2008;15:2321-2328.
54. Salloway S, Mintzer J, Weiner MF, Cummings JL. Disease-modifying therapies in Alzheimer’s disease. Alzheimers Dement. 2008;4:65-79.
55. Jellinger KA. The pathology of “vascular dementia”: a critical update. J Alzheimers Dis. 2008;14:107-123.
56. Trojanowski JQ, Duff K, Fillit H, et al; Frontotemporal Dementia (FTD) Working Group on FTD Drug Discovery. New directions for frontotemporal dementia drug discovery. Alzheimers Dement. 2008;4:89-93.
57. Farlow MR, Cummings J. A modern hypothesis: the distinct pathologies of dementia associated with Parkinson’s disease versus Alzheimer’s disease. Dement Geriatr Cogn Disord. 2008;25:301-308.
58. Lee SJ. Origins and effects of extracellular alpha-synuclein: implications in Parkinson’s disease. J Mol Neurosci. 2008;34:17-22.
59. Imarisio S, Carmichael J, Korolchuk V, et al. Huntington’s disease: from pathology and genetics to potential therapies. Biochem J. 2008;412:191-209.

Dementia: A Focused Review

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