Cognition in Alzheimer s disease

Watson GS, Bernhardt T, Reger MA, Cholerton BA, Baker LD, Peskind ER, Asthana S, Plymate SR, Frolich L, Craft S (2006) Insulin effects on CSF norepinephrine and cognition in Alzheimer s disease. Neurobiol. Aging 27 38-41. 

Thai LJ, Forrest M, Loft H, Mengel H (2000) Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer s disease. Neurology 54 421 26... 

Hock, C., Konietzko, U., Streffer, J. R. et al. Antibodies against (3-amyloid slow cognitive decline in Alzheimer s disease. Neuron 38 547-554,2003. 

Treatment Options for Cognitive Symptoms in Alzheimer s Disease... 

Cognitive deficits in Alzheimer s disease Attention deficits are a core feature of Alzheimer s disease (Lawrence and Sahakian 1995). Problems arise primarily from divided and disengaging/shifting attention and less from focusing of attention (Nebes 1997). Language deficits are seen early in the course of Alzheimer s disease. While grammar is relatively intact, there is a deficit in expression and comprehension of semantic meaning. 

Frontotemporal dementias are characterized by gross structural changes in the frontal and anterior temporal lobes, metabolic disturbances, and involvement of certain subcortical structures as well (Ishii et al. 1998). Whereas in Alzheimer s disease the early cognitive disturbances are in memory, in frontotemporal dementias the early manifestations are in executive and behavioral function (Pfeffer et al. 1999 Varma et al. 1999). This relative cognitive distinction persists throughout the course of the two disorders (Pachana et al. 1996). Disinhibition and disorganization are common, and psychotic symptoms may be prominent in frontotemporal dementia. 

Raffaele KC, Asthana S, Berardi A, Haxby JV, Morris PP, Schapiro MB, SoncrantTT. (1996). Differential response to the cholinergic agonist arecoline among different cognitive modalities in Alzheimer s disease. Neuropsychopharmacology. 15(2) 163-70. 

Robbins TW, McAlonan G, Muir JL, Everitt BJ. (1997). Cognitive enhancers in theory and practice studies of the cholinergic hypothesis of cognitive deficits in Alzheimer s disease. Behav Brain Res. 83(1-2) 15-23. 

White HK, Levin ED. (1999). Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer s disease. Psychopharmacology (Berlin). 143(2) 158-65. 

Fig. 10.7 Brain mapping activity (theta band) according to Global Deterioration Stage (GDS) staging (cognitive deterioration) and apolipoprotein E (APOE) genotype in Alzheimer s disease. (From refs. 19 and 20.)...

Cacabelos, R. (2007) Molecular pathology and pharmacogenomics in Alzheimer s disease Polygenic-related effects of multifactorial treatments on cognition, anxiety, and depression. Meth. Find. Exper. Clin. Pharmacol., 29(suppl. B), 1-91. 

Doody, R.S., Dunn, J.K., Clark, C.M., et al. (2001) Chronic donepezil treatment is associated with slowed cognitive decline in Alzheimer s disease. Dement. Geriatr. Cogn. Disord., 12, 295-300. 

Ahmed, N., Ahmed, U., Thornalley, P. J., Hager, K., Fleischer, G., and Munch, G. (2005). Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer s disease and link to cognitive impairment. ]. Neurochem. 92, 255-263. 

Table 1. Core cognitive deficits in Alzheimer s disease.

The concept of bradyphrenia overlaps with that of apathy, defined as diminished motivation not attributable to diminished level of consciousness, cognitive impairment or emotional distress (Marin, 1990). Apathy is common in neurodegenerative disorders and is associated with orbito-frontal, medial frontal and anterior temporal dysfunction in Alzheimer s disease (Craig et al., 1996). Apathy is one of the most common neuropsychiatric symptoms in PD, and correlates with executive dysfunction (Aarsland, 1999b). However, apathy is even more common in PSP patients (Aarsland et al., 2001c), possibly related to the more marked involvement of the orbitofrontal and medial frontal circuits in PSP than in PD. 

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